dataset_id
large_stringclasses
414 values
reaction_id
large_stringlengths
36
36
reaction_smiles
large_stringlengths
4
873
rxn_insight_reaction
large_stringlengths
19
1.07k
mapped_reaction_smiles
large_stringlengths
14
3.37k
reactant_smiles
large_stringlengths
1
581
product_smiles
large_stringlengths
1
433
reagent_smiles
large_stringclasses
634 values
catalyst_smiles
large_stringlengths
1
683
solvent_smiles
large_stringlengths
1
245
rxn_insight_class
large_stringclasses
11 values
rxn_insight_name
large_stringclasses
346 values
rxn_insight_tag
large_stringlengths
64
64
rxn_insight_tag2
large_stringlengths
64
64
rxn_insight_scaffold
large_stringlengths
5
288
rxn_insight_template
large_stringlengths
24
2.64k
yield_percent
float64
-0.8
90,205,160,000B
yield_measurements
large_stringlengths
2
864
temperature_value
float64
-230
30.1k
temperature_units
large_stringclasses
3 values
reaction_time_value
float64
0
4k
time_units
large_stringclasses
4 values
procedure_details
large_stringlengths
1
23.6k
reference
large_stringclasses
96 values
doi
large_stringclasses
19 values
functional_groups_reactants
large_stringlengths
3
716
functional_groups_products
large_stringlengths
3
539
participating_rings_reactants
large_stringlengths
5
293
participating_rings_products
large_stringlengths
5
271
all_rings_products
large_stringlengths
5
271
byproduct_smiles
large_stringclasses
176 values
agent_smiles
large_stringlengths
1
712
temperature_c
float64
-230
30.1k
reaction_time_hours
float64
0
2.16k
reaction_smiles_with_agents
large_stringlengths
4
882
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-ab7b8d70f4d6495f995fc35087a3a344
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Oc1ccc2c(Cl)ccnc2c1>>COc1cc2c(Oc3ccc4c(Cl)ccnc4c3)ncnc2cc1OCCCN1CCOCC1
ClC1=CC=NC2=CC(=CC=C12)O.ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1.ClC1=CC=NC2=CC(=CC=C12)O.C([O-])([O-])=O.[K+].[K+]>>ClC1=CC=NC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:24]([O:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)[cH:23][c:22]2[n:21][cH:20][n:19]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[c:12]([Cl:13])[cH:14][cH:15][n:16][c:17]2[cH:18]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[c:12]([Cl:...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Oc1ccc2c(Cl)ccnc2c1
COc1cc2c(Oc3ccc4c(Cl)ccnc4c3)ncnc2cc1OCCCN1CCOCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1cnc2cc(Oc3ncnc4cc(OCCCN5CCOCC5)ccc34)ccc2c1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#7;a:9]:[c:10]:[c:11]:[c:12](-[OH;D1;+0:13]):[c:14]>>[#7;a:9]:[c:10]:[c:11]:[c:12](-[O;H0;D2;+0:13]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:14]
47
[{"value": 47.0, "product": "ClC1=CC=NC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 46.6, "product": "ClC1=CC=NC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
30
MINUTE
To 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (250 mg, 0.74 mmol), (prepared as described for the starting material in Example 1), in suspension in DMF (4 ml) were successively added 4-chloro-7-hydroxyquinoline (133 mg, 0.74 mmol) and potassium carbonate (153 mg, 1 mmol) and the reaction mixture heated to 10...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncccc2c1.c1ccc2ncncc2c1.C1COCC[NH]1
HCl
CN(C)C=O
100
0.5
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Oc1ccc2c(Cl)ccnc2c1>CN(C)C=O>COc1cc2c(Oc3ccc4c(Cl)ccnc4c3)ncnc2cc1OCCCN1CCOCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d53e2547fb874bd493ae351e58fef713
Clc1ccnc2cc(OCc3ccccc3)ccc12>>Oc1ccc2c(Cl)ccnc2c1
C(C1=CC=CC=C1)OC1=CC=C2C(=CC=NC2=C1)Cl.C(O)([O-])=O.[Na+]>>ClC1=CC=NC2=CC(=CC=C12)O
c1ccc(C[O:1][c:2]2[cH:3][cH:4][c:5]3[c:6]([Cl:7])[cH:8][cH:9][n:10][c:11]3[cH:12]2)cc1>>[OH:1][c:2]1[cH:3][cH:4][c:5]2[c:6]([Cl:7])[cH:8][cH:9][n:10][c:11]2[cH:12]1
Clc1ccnc2cc(OCc3ccccc3)ccc12
Oc1ccc2c(Cl)ccnc2c1
null
null
C(=O)(C(F)(F)F)O
Deprotection
Hydroxyl benzyl deprotection
36869d1fe85185a14d9eb30bf05178c600a9b6eca277ffaf3803578c30e0bf5d
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2ncccc2c1
[#7;a:1]:[c:2]:[c:3]:[c:4](-[O;H0;D2;+0:5]-C-c1:c:c:c:c:c:1):[c:6]>>[#7;a:1]:[c:2]:[c:3]:[c:4](-[OH;D1;+0:5]):[c:6]
98
[{"value": 98.0, "product": "ClC1=CC=NC2=CC(=CC=C12)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 97.9, "product": "ClC1=CC=NC2=CC(=CC=C12)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
A solution of 7-benzyloxy-4-chloroquinoline (17 g, 56 mmol), (Konishi et al. WO 96/11187), in TFA (170 ml) was heated at reflux for 2 hours. The solvent was removed under vacuum and the residue was triturated with ether, filtered and washed with ether. The solid was suspended in an aqueous solution of sodium hydrogen c...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
c1ccccc1
null
c1ccc2ncccc2c1
Other
C(=O)(C(F)(F)F)O
null
0.5
Clc1ccnc2cc(OCc3ccccc3)ccc12>C(=O)(C(F)(F)F)O>Oc1ccc2c(Cl)ccnc2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-ea6322402661414aa9a77b99040c3dc8
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Oc1ccc2ccccc2c1>>COc1cc2c(Oc3ccc4ccccc4c3)ncnc2cc1OCC1CCN(C)CC1
C(Cl)Cl.ClC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C.OC1=CC2=CC=CC=C2C=C1.C([O-])([O-])=O.[K+].[K+]>>COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C)OC1=CC2=CC=CC=C2C=C1
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:23]([O:24][CH2:25][CH:26]3[CH2:27][CH2:28][N:29]([CH3:30])[CH2:31][CH2:32]3)[cH:22][c:21]2[n:20][cH:19][n:18]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[cH:12][cH:13][cH:14][cH:15][c:16]2[cH:17]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[cH:12][cH:13][cH:14][c...
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Oc1ccc2ccccc2c1
COc1cc2c(Oc3ccc4ccccc4c3)ncnc2cc1OCC1CCN(C)CC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1ccc2cc(Oc3ncnc4cc(OCC5CCNCC5)ccc34)ccc2c1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
83
[{"value": 83.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C)OC1=CC2=CC=CC=C2C=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 81.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C)OC1=CC2=CC=CC=C2C=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
3.5
HOUR
A solution of 4-chloro-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazoline (74 mg, 0.23 mmol), (prepared as described for the starting material in Example 10), and 2-hydroxynaphthalene (40 mg, 0.28 mmol) in DMF (1.5 ml) containing potassium carbonate (48 mg, 0.35 mmol) was stirred at 100° C. for 3.5 hours. After c...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ccccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
CN(C)C=O
100
3.5
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Oc1ccc2ccccc2c1>CN(C)C=O>COc1cc2c(Oc3ccc4ccccc4c3)ncnc2cc1OCC1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-5ead54da921b4c8c9f7bda41c38444cd
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Nc1ccc2c(c1)OCO2>>COc1cc2c(Nc3ccc4c(c3)OCO4)ncnc2cc1OCCCN1CCOCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1.C1OC=2C=C(N)C=CC2O1.Cl>>O1COC2=C1C=CC(=C2)NC2=NC=NC1=CC(=C(C=C21)OC)OCCCN2CCOCC2
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:22]([O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[cH:21][c:20]2[n:19][cH:18][n:17]1.[NH2:7][c:8]1[cH:9][cH:10][c:11]2[c:12]([cH:13]1)[O:14][CH2:15][O:16]2>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]3[cH:9][cH:10][c:11]4[c:12]([cH:13]3)[O:14]...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Nc1ccc2c(c1)OCO2
COc1cc2c(Nc3ccc4c(c3)OCO4)ncnc2cc1OCCCN1CCOCC1
null
null
C(C)(C)O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1nc(Nc2ccc3c(c2)OCO3)c2ccc(OCCCN3CCOCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[NH2;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[NH;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
81.3
[{"value": 76.0, "product": "O1COC2=C1C=CC(=C2)NC2=NC=NC1=CC(=C(C=C21)OC)OCCCN2CCOCC2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 81.3, "product": "O1COC2=C1C=CC(=C2)NC2=NC=NC1=CC(=C(C=C21)OC)OCCCN2CCOCC2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (74 mg, 0.23 mmol), (prepared as described for the starting material in Example 1), and 3,4-(methylenedioxy)aniline (53 mg, 0.24 mmol) in a solution of isopropanol (3.5 ml) containing 5.5M hydrogen chloride in isopropanol (42 μl) was heated for 3 hours...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2c(c1)OCO2.c1ccc2ncncc2c1.C1COCC[NH]1
HCl
C(C)(C)O
null
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Nc1ccc2c(c1)OCO2>C(C)(C)O>COc1cc2c(Nc3ccc4c(c3)OCO4)ncnc2cc1OCCCN1CCOCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b3882d707985453f8a9340c245ee6b06
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Cc1cc(=O)c2ccc(O)cc2o1>>COc1cc2c(Oc3ccc4c(=O)cc(C)oc4c3)ncnc2cc1OCC1CCN(C)CC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C.OC1=CC=C2C(C=C(OC2=C1)C)=O.C([O-])([O-])=O.[K+].[K+]>>COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C)OC1=CC=C2C(C=C(OC2=C1)C)=O
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:25]([O:26][CH2:27][CH:28]3[CH2:29][CH2:30][N:31]([CH3:32])[CH2:33][CH2:34]3)[cH:24][c:23]2[n:22][cH:21][n:20]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[c:12](=[O:13])[cH:14][c:15]([CH3:16])[o:17][c:18]2[cH:19]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[c:12](...
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Cc1cc(=O)c2ccc(O)cc2o1
COc1cc2c(Oc3ccc4c(=O)cc(C)oc4c3)ncnc2cc1OCC1CCN(C)CC1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
O=c1ccoc2cc(Oc3ncnc4cc(OCC5CCNCC5)ccc34)ccc12
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#8;a:9]:[c:10]:[c:11]:[c:12](-[OH;D1;+0:13]):[c:14]>>[#8;a:9]:[c:10]:[c:11]:[c:12](-[O;H0;D2;+0:13]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:14]
92.1
[{"value": 92.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C)OC1=CC=C2C(C=C(OC2=C1)C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 92.1, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C)OC1=CC=C2C(C=C(OC2=C1)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
null
null
A suspension of 4-chloro-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (130 mg, 0.4 mmol), (prepared as described for the starting material in Example 10), 7-hydroxy-2-methylchromone (88 mg, 0.5 mmol), (Bull Soc. Chim. Fr. 1995, 132, 233), and potassium carbonate (83 mg, 0.6 mmol) was heated at 100° C. for 1.5...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2cccoc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
null
100
null
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Cc1cc(=O)c2ccc(O)cc2o1>>COc1cc2c(Oc3ccc4c(=O)cc(C)oc4c3)ncnc2cc1OCC1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-733f6a2c3eaf44c49e3d49aebedf0468
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Oc1ccc2[nH]ccc2c1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCC1CCN(C)CC1
O.ClC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C.OC=1C=C2C=CNC2=CC1.C([O-])([O-])=O.[K+].[K+]>>N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:22]([O:23][CH2:24][CH:25]3[CH2:26][CH2:27][N:28]([CH3:29])[CH2:30][CH2:31]3)[cH:21][c:20]2[n:19][cH:18][n:17]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][cH:13][cH:14][c:15]2[cH:16]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][cH:13][cH:14][c:15]4[c...
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Oc1ccc2[nH]ccc2c1
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCC1CCN(C)CC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCC3CCNCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
64
[{"value": 64.0, "product": "N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 63.3, "product": "N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
null
null
A solution of 4-chloro-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (110 mg, 0.34 mmol), (prepared as described for the starting material in Example 10), and 5-hydroxyindole (55 mg, 0.41 mmol) in DMF (1.5 ml) containing potassium carbonate (70 mg, 0.51 mmol) was heated at 100° C. for 2 hours. After cooling, w...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
CN(C)C=O
100
null
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Oc1ccc2[nH]ccc2c1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCC1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-c7c6aa780474464098c7bfbbaec7ba8d
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Cc1[nH]c2ccc(O)cc2c1C>>COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCC1CCN(C)CC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C.CC=1NC2=CC=C(C=C2C1C)O>>CC=1NC2=CC=C(C=C2C1C)OC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:24]([O:25][CH2:26][CH:27]3[CH2:28][CH2:29][N:30]([CH3:31])[CH2:32][CH2:33]3)[cH:23][c:22]2[n:21][cH:20][n:19]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][c:13]([CH3:14])[c:15]([CH3:16])[c:17]2[cH:18]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13...
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Cc1[nH]c2ccc(O)cc2c1C
COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCC1CCN(C)CC1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCC3CCNCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
40
[{"value": 40.0, "product": "CC=1NC2=CC=C(C=C2C1C)OC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 39.5, "product": "CC=1NC2=CC=C(C=C2C1C)OC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 34, 4-chloro-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (110 mg, 0.34 mmol), (prepared as described for the starting material in Example 10), was reacted with 2,3-dimethyl-5-hydroxyindole (66 mg, 0.41 mmol), (Arch. Pharm. 1972, 305, 159). The crude p...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
null
null
null
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Cc1[nH]c2ccc(O)cc2c1C>>COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCC1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-c40490e235804b9f9e191e661cd968ee
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1ccc2[nH]ccc2c1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCCCN1CCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1.OC=1C=C2C=CNC2=CC1>>N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:22]([O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][CH2:30][CH2:31]3)[cH:21][c:20]2[n:19][cH:18][n:17]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][cH:13][cH:14][c:15]2[cH:16]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][cH:13][cH:14][c:15]4[cH...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1ccc2[nH]ccc2c1
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCCCN1CCCC1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
50
[{"value": 50.0, "product": "N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 49.2, "product": "N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 34, 4-chloro-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline (10 mg, 0.34 mmol), (prepared as described for the starting material in Example 9), was reacted with 5-hydroxyindole (55 mg, 0.41 mmol). The crude product was purified by chromatography on alumina, e...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]C1
HCl
null
null
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1ccc2[nH]ccc2c1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCCCN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-19ddd9522a2c45959f0bb35aaef8f53e
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Cc1[nH]c2ccc(N)cc2c1C>>COc1cc2c(Nc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCC1CCN(C)CC1
Cl.ClC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C.NC=1C=C2C(=C(NC2=CC1)C)C>>Cl.CC=1NC2=CC=C(C=C2C1C)NC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:24]([O:25][CH2:26][CH:27]3[CH2:28][CH2:29][N:30]([CH3:31])[CH2:32][CH2:33]3)[cH:23][c:22]2[n:21][cH:20][n:19]1.[NH2:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][c:13]([CH3:14])[c:15]([CH3:16])[c:17]2[cH:18]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:...
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Cc1[nH]c2ccc(N)cc2c1C
COc1cc2c(Nc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCC1CCN(C)CC1
null
null
C(C)(C)O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1nc(Nc2ccc3[nH]ccc3c2)c2ccc(OCC3CCNCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[NH2;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[NH;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
79
[{"value": 74.0, "product": "Cl.CC=1NC2=CC=C(C=C2C1C)NC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 79.0, "product": "Cl.CC=1NC2=CC=C(C=C2C1C)NC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
70
CELSIUS
null
null
A suspension of 4-chloro-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (100 mg, 0.31 mmol), (prepared as described for the starting material in Example 10), and 5-amino-2,3-dimethylindole (55 mg, 0.34 mmol) in isopropanol (6 ml) containing 5.5M hydrogen choride in isopropanol (60 μL) was heated for 30 minutes ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
C(C)(C)O
70
null
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Cc1[nH]c2ccc(N)cc2c1C>C(C)(C)O>COc1cc2c(Nc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCC1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a64612f1488145b3a1017e0a6b4aac55
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1[nH]c2ccc(N)cc2c1C>>COc1cc2c(Nc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCCCN1CCCC1.Cl
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1.NC=1C=C2C(=C(NC2=CC1)C)C>>Cl.CC=1NC2=CC=C(C=C2C1C)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([Cl:34])[n:19][cH:20][n:21][c:22]2[cH:23][c:24]1[O:25][CH2:26][CH2:27][CH2:28][N:29]1[CH2:30][CH2:31][CH2:32][CH2:33]1.[NH2:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][c:13]([CH3:14])[c:15]([CH3:16])[c:17]2[cH:18]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1[nH]c2ccc(N)cc2c1C
COc1cc2c(Nc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCCCN1CCCC1.Cl
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1nc(Nc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCCC3)cc2n1
[Cl;H0;D1;+0:1]-[c;H0;D3;+0:2]1:[#7;a:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[ClH;D0;+0:1].[c:12]:[c:11](-[NH;D2;+0:10]-[c;H0;D3;+0:2]1:[#7;a:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]):[c:13]
76.3
[{"value": 72.0, "product": "Cl.CC=1NC2=CC=C(C=C2C1C)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 76.3, "product": "Cl.CC=1NC2=CC=C(C=C2C1C)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 37, 4-chloro-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline (100 mg, 0.31 mmol), (prepared as described for the starting material in Example 9), was reacted with 5-amino-2,3-dimethylindole (55 mg, 0.34 mmol) to give 4(2,3-dimethylindol-5-ylamino)-6-methoxy-7-...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]C1
null
null
null
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1[nH]c2ccc(N)cc2c1C>>COc1cc2c(Nc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCCCN1CCCC1.Cl
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-f0c1a689d76a40c7a36e8a94ad814beb
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1cc2cc(N)ccc2[nH]1>>COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCCC1.Cl
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1.NC=1C=C2C=C(NC2=CC1)C>>Cl.COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCC1)NC=1C=C2C=C(NC2=CC1)C
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([Cl:33])[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[O:24][CH2:25][CH2:26][CH2:27][N:28]1[CH2:29][CH2:30][CH2:31][CH2:32]1.[NH2:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][c:13]([CH3:14])[cH:15][c:16]2[cH:17]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1cc2cc(N)ccc2[nH]1
COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCCC1.Cl
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1nc(Nc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCCC3)cc2n1
[Cl;H0;D1;+0:1]-[c;H0;D3;+0:2]1:[#7;a:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[ClH;D0;+0:1].[c:12]:[c:11](-[NH;D2;+0:10]-[c;H0;D3;+0:2]1:[#7;a:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]):[c:13]
95.1
[{"value": 89.0, "product": "Cl.COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCC1)NC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 95.1, "product": "Cl.COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCC1)NC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 38, 4-chloro-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline (100 mg, 0.31 mmol), (prepared as described for the starting material in Example 9), was reacted with 5-amino-2-methylindole (50 mg, 0.34 mmol) to give 6-methoxy-4-(2-methylindol-5-ylamino)-7-(3-pyrr...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]C1
null
null
null
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1cc2cc(N)ccc2[nH]1>>COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCCC1.Cl
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-aabebf6e59a24b7097a02e84c979c5a4
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1cc(C)c2ccc(O)cc2n1>>COc1cc2c(Oc3ccc4c(C)cc(C)nc4c3)ncnc2cc1OCCCN1CCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1.OC1=CC=C2C(=CC(=NC2=C1)C)C.C([O-])([O-])=O.[K+].[K+]>>CC1=NC2=CC(=CC=C2C(=C1)C)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:25]([O:26][CH2:27][CH2:28][CH2:29][N:30]3[CH2:31][CH2:32][CH2:33][CH2:34]3)[cH:24][c:23]2[n:22][cH:21][n:20]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[c:12]([CH3:13])[cH:14][c:15]([CH3:16])[n:17][c:18]2[cH:19]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[c:12](...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1cc(C)c2ccc(O)cc2n1
COc1cc2c(Oc3ccc4c(C)cc(C)nc4c3)ncnc2cc1OCCCN1CCCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1cnc2cc(Oc3ncnc4cc(OCCCN5CCCC5)ccc34)ccc2c1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#7;a:9]:[c:10]:[c:11]:[c:12](-[OH;D1;+0:13]):[c:14]>>[#7;a:9]:[c:10]:[c:11]:[c:12](-[O;H0;D2;+0:13]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:14]
35.2
[{"value": 35.0, "product": "CC1=NC2=CC(=CC=C2C(=C1)C)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 35.2, "product": "CC1=NC2=CC(=CC=C2C(=C1)C)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
90
CELSIUS
null
null
A mixture of 4-chloro-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline (100 mg, 0.31 mmol), (prepared as described for the starting material in Example 9), and 7-hydroxy-2,4-dimethylquinoline (64 mg, 0.36 mmol), (Chem. Berichte, 1903, 36, 4016), in DMF (3 ml) containing potassium carbonate (86 mg, 0.62 mmol) was heate...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncccc2c1.c1ccc2ncncc2c1.C1CC[NH]C1
HCl
CN(C)C=O
90
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1cc(C)c2ccc(O)cc2n1>CN(C)C=O>COc1cc2c(Oc3ccc4c(C)cc(C)nc4c3)ncnc2cc1OCCCN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-bda7ad14238d46d198d97acd5d1b374a
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Cc1cc2cc(N)ccc2[nH]1>>COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCN(C)CC1.Cl
ClC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C.NC=1C=C2C=C(NC2=CC1)C>>Cl.COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C)NC=1C=C2C=C(NC2=CC1)C
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([Cl:33])[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[O:24][CH2:25][CH:26]1[CH2:27][CH2:28][N:29]([CH3:30])[CH2:31][CH2:32]1.[NH2:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][c:13]([CH3:14])[cH:15][c:16]2[cH:17]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([C...
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Cc1cc2cc(N)ccc2[nH]1
COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCN(C)CC1.Cl
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1nc(Nc2ccc3[nH]ccc3c2)c2ccc(OCC3CCNCC3)cc2n1
[Cl;H0;D1;+0:1]-[c;H0;D3;+0:2]1:[#7;a:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[ClH;D0;+0:1].[c:12]:[c:11](-[NH;D2;+0:10]-[c;H0;D3;+0:2]1:[#7;a:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]):[c:13]
99.3
[{"value": 99.3, "product": "Cl.COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C)NC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 37, 4-chloro-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (50 mg, 0.155 mmol), (prepared as described for the starting material in Example 10), was reacted with 5-amino-2-methylindole (0.171 mmol) to give 6-methoxy-4-(2-methylindol-5-ylamino)-7-(1-meth...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
null
null
null
null
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Cc1cc2cc(N)ccc2[nH]1>>COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCN(C)CC1.Cl
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d7023257e4b74c068b11b0748425a934
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1ccc2ccc(O)cc2n1>>COc1cc2c(Oc3ccc4ccc(C)nc4c3)ncnc2cc1OCCCN1CCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1.OC1=CC=C2C=CC(=NC2=C1)C.C([O-])([O-])=O.[K+].[K+]>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCC1)OC1=CC=C2C=CC(=NC2=C1)C
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:24]([O:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:30][CH2:31][CH2:32][CH2:33]3)[cH:23][c:22]2[n:21][cH:20][n:19]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[cH:12][cH:13][c:14]([CH3:15])[n:16][c:17]2[cH:18]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[cH:12][cH:13][c...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1ccc2ccc(O)cc2n1
COc1cc2c(Oc3ccc4ccc(C)nc4c3)ncnc2cc1OCCCN1CCCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1cnc2cc(Oc3ncnc4cc(OCCCN5CCCC5)ccc34)ccc2c1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#7;a:9]:[c:10]:[c:11]:[c:12](-[OH;D1;+0:13]):[c:14]>>[#7;a:9]:[c:10]:[c:11]:[c:12](-[O;H0;D2;+0:13]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:14]
69
[{"value": 69.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCC1)OC1=CC=C2C=CC(=NC2=C1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 68.9, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCC1)OC1=CC=C2C=CC(=NC2=C1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
90
CELSIUS
null
null
A suspension of 4-chloro-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline (100 mg, 0.31 mmol), (prepared as described for the starting material in Example 9), and 7-hydroxy-2-methylquinoline (54 mg, 0.34 mmol), (J. Med. Chem. 1998, 41, 4062), in DMF (3 ml) containing potassium carbonate (86 mg, 0.62 mmol) was heated a...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncccc2c1.c1ccc2ncncc2c1.C1CC[NH]C1
HCl
CN(C)C=O
90
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1ccc2ccc(O)cc2n1>CN(C)C=O>COc1cc2c(Oc3ccc4ccc(C)nc4c3)ncnc2cc1OCCCN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-8f8b1220b3c543f5aee2364d26d2c395
COc1cc2c(Cl)ncnc2cc1OCC1CCN(CCS(C)(=O)=O)CC1.Cc1ccc2ccc(O)cc2n1>>COc1cc2c(Oc3ccc4ccc(C)nc4c3)ncnc2cc1OCC1CCN(CCS(C)(=O)=O)CC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)CCS(=O)(=O)C.OC1=CC=C2C=CC(=NC2=C1)C>>COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)CCS(=O)(=O)C)OC1=CC=C2C=CC(=NC2=C1)C
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:24]([O:25][CH2:26][CH:27]3[CH2:28][CH2:29][N:30]([CH2:31][CH2:32][S:33]([CH3:34])(=[O:35])=[O:36])[CH2:37][CH2:38]3)[cH:23][c:22]2[n:21][cH:20][n:19]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[cH:12][cH:13][c:14]([CH3:15])[n:16][c:17]2[cH:18]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][...
COc1cc2c(Cl)ncnc2cc1OCC1CCN(CCS(C)(=O)=O)CC1.Cc1ccc2ccc(O)cc2n1
COc1cc2c(Oc3ccc4ccc(C)nc4c3)ncnc2cc1OCC1CCN(CCS(C)(=O)=O)CC1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1cnc2cc(Oc3ncnc4cc(OCC5CCNCC5)ccc34)ccc2c1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#7;a:9]:[c:10]:[c:11]:[c:12](-[OH;D1;+0:13]):[c:14]>>[#7;a:9]:[c:10]:[c:11]:[c:12](-[O;H0;D2;+0:13]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:14]
82
[{"value": 82.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)CCS(=O)(=O)C)OC1=CC=C2C=CC(=NC2=C1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 81.4, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)CCS(=O)(=O)C)OC1=CC=C2C=CC(=NC2=C1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 42, 4-chloro-6-methoxy-7-(1-(2-methylsulphonylethyl)piperidin-4-ylmethoxy)quinazoline (156 mg, 0.38 mmol), (prepared as described for the starting material in Example 12), was reacted with 7-hydroxy-2-methylquinoline (66 mg, 0.4 mmol), (J. Med. Chem. 1998, 41, 4...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
null
null
null
COc1cc2c(Cl)ncnc2cc1OCC1CCN(CCS(C)(=O)=O)CC1.Cc1ccc2ccc(O)cc2n1>>COc1cc2c(Oc3ccc4ccc(C)nc4c3)ncnc2cc1OCC1CCN(CCS(C)(=O)=O)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-62bde8e5c40c43e7be7f0f6a31a9b042
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Oc1ccc2[nH]c(C(F)(F)F)cc2c1>>COc1cc2c(Oc3ccc4[nH]c(C(F)(F)F)cc4c3)ncnc2cc1OCC1CCN(C)CC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C.OC=1C=C2C=C(NC2=CC1)C(F)(F)F.C([O-])([O-])=O.[K+].[K+]>>COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C)OC=1C=C2C=C(NC2=CC1)C(F)(F)F
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:26]([O:27][CH2:28][CH:29]3[CH2:30][CH2:31][N:32]([CH3:33])[CH2:34][CH2:35]3)[cH:25][c:24]2[n:23][cH:22][n:21]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][c:13]([C:14]([F:15])([F:16])[F:17])[cH:18][c:19]2[cH:20]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[...
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Oc1ccc2[nH]c(C(F)(F)F)cc2c1
COc1cc2c(Oc3ccc4[nH]c(C(F)(F)F)cc4c3)ncnc2cc1OCC1CCN(C)CC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCC3CCNCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
48
[{"value": 48.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C)OC=1C=C2C=C(NC2=CC1)C(F)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 46.4, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C)OC=1C=C2C=C(NC2=CC1)C(F)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
90
CELSIUS
null
null
A suspension of 4-chloro-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (50 mg, 0.155 mmol), (prepared as described for the starting material in Example 10), and 5-hydroxy-2-trifluoromethylindole (34 mg, 0.17 mmol) in DMF (1.5 ml) containing potassium carbonate (43 mg, 0.31 mmol) was heated at 90° C. for 2 hour...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
CN(C)C=O
90
null
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Oc1ccc2[nH]c(C(F)(F)F)cc2c1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C(F)(F)F)cc4c3)ncnc2cc1OCC1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-2fc861487edd4918bf21ab23242d9513
COc1ccc2[nH]c(C(F)(F)F)cc2c1>>Oc1ccc2[nH]c(C(F)(F)F)cc2c1
COC=1C=C2C=C(NC2=CC1)C(F)(F)F.B(Br)(Br)Br.C(O)([O-])=O.[Na+]>>OC=1C=C2C=C(NC2=CC1)C(F)(F)F
C[O:1][c:2]1[cH:3][cH:4][c:5]2[nH:6][c:7]([C:8]([F:9])([F:10])[F:11])[cH:12][c:13]2[cH:14]1>>[OH:1][c:2]1[cH:3][cH:4][c:5]2[nH:6][c:7]([C:8]([F:9])([F:10])[F:11])[cH:12][c:13]2[cH:14]1
COc1ccc2[nH]c(C(F)(F)F)cc2c1
Oc1ccc2[nH]c(C(F)(F)F)cc2c1
null
null
C(Cl)Cl
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2[nH]ccc2c1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[OH;D1;+0:1]-[c:2](:[c:3]):[c:4]
39
[{"value": 39.0, "product": "OC=1C=C2C=C(NC2=CC1)C(F)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 39.0, "product": "OC=1C=C2C=C(NC2=CC1)C(F)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
45
MINUTE
A solution of 5-methoxy-2-trifluoromethylindole (800 mg, 3.7 mmol) in methylene chloride (6 ml) was cooled to −15° C. and a solution of 1M boron tribromide in methylene chloride (7.44 ml, 7.4 mmol) was added in portions. The mixture was allowed to warm to ambient temperature and was stirred for 45 minutes. After coolin...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1ccc2[nH]ccc2c1
Other
C(Cl)Cl
null
0.75
COc1ccc2[nH]c(C(F)(F)F)cc2c1>C(Cl)Cl>Oc1ccc2[nH]c(C(F)(F)F)cc2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a3c232ef77384535b4420dbb140115b3
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1ccc2[nH]c(C(F)(F)F)cc2c1>>COc1cc2c(Oc3ccc4[nH]c(C(F)(F)F)cc4c3)ncnc2cc1OCCCN1CCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1.OC=1C=C2C=C(NC2=CC1)C(F)(F)F>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCC1)OC=1C=C2C=C(NC2=CC1)C(F)(F)F
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:26]([O:27][CH2:28][CH2:29][CH2:30][N:31]3[CH2:32][CH2:33][CH2:34][CH2:35]3)[cH:25][c:24]2[n:23][cH:22][n:21]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][c:13]([C:14]([F:15])([F:16])[F:17])[cH:18][c:19]2[cH:20]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[n...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1ccc2[nH]c(C(F)(F)F)cc2c1
COc1cc2c(Oc3ccc4[nH]c(C(F)(F)F)cc4c3)ncnc2cc1OCCCN1CCCC1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
71.9
[{"value": 70.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCC1)OC=1C=C2C=C(NC2=CC1)C(F)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 71.9, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCC1)OC=1C=C2C=C(NC2=CC1)C(F)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 44, 4-chloro-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline (100 mg, 0.3 mmol), (prepared as described for the starting material in Example 9), was reacted with 5-hydroxy-2-trifluoromethylindole (75 mg, 0.37 mmol), (prepared as described for the starting mate...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]C1
HCl
null
null
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1ccc2[nH]c(C(F)(F)F)cc2c1>>COc1cc2c(Oc3ccc4[nH]c(C(F)(F)F)cc4c3)ncnc2cc1OCCCN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-2e01c4278d8a4ffc9f7a54bfa168e355
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Cc1ccc2ccc(O)cc2n1>>COc1cc2c(Oc3ccc4ccc(C)nc4c3)ncnc2cc1OCC1CCN(C)CC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C.OC1=CC=C2C=CC(=NC2=C1)C>>COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C)OC1=CC=C2C=CC(=NC2=C1)C
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:24]([O:25][CH2:26][CH:27]3[CH2:28][CH2:29][N:30]([CH3:31])[CH2:32][CH2:33]3)[cH:23][c:22]2[n:21][cH:20][n:19]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[cH:12][cH:13][c:14]([CH3:15])[n:16][c:17]2[cH:18]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[cH:12][cH:13][...
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Cc1ccc2ccc(O)cc2n1
COc1cc2c(Oc3ccc4ccc(C)nc4c3)ncnc2cc1OCC1CCN(C)CC1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1cnc2cc(Oc3ncnc4cc(OCC5CCNCC5)ccc34)ccc2c1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#7;a:9]:[c:10]:[c:11]:[c:12](-[OH;D1;+0:13]):[c:14]>>[#7;a:9]:[c:10]:[c:11]:[c:12](-[O;H0;D2;+0:13]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:14]
63
[{"value": 63.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C)OC1=CC=C2C=CC(=NC2=C1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 62.4, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C)OC1=CC=C2C=CC(=NC2=C1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 42, 4-chloro-6-methoxy-7-(1-methylpiperidin-4-ylmethoxy)quinazoline (100 mg, 0.31 mmol), (prepared as described for the starting material in Example 10), was reacted with 7-hydroxy-2-methylquinoline (54 mg, 0.34 mmol), (J. Med. Chem. 1998, 41, 4062), to give 6-m...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
null
null
null
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Cc1ccc2ccc(O)cc2n1>>COc1cc2c(Oc3ccc4ccc(C)nc4c3)ncnc2cc1OCC1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-6cee24b781e3485797a09bfb9bcee4b3
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1[nH]c2ccc(O)cc2c1C>>COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCCCN1CCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1.CC=1NC2=CC=C(C=C2C1C)O.C([O-])([O-])=O.[K+].[K+]>>CC=1NC2=CC=C(C=C2C1C)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:24]([O:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:30][CH2:31][CH2:32][CH2:33]3)[cH:23][c:22]2[n:21][cH:20][n:19]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][c:13]([CH3:14])[c:15]([CH3:16])[c:17]2[cH:18]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1[nH]c2ccc(O)cc2c1C
COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCCCN1CCCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
33
[{"value": 33.0, "product": "CC=1NC2=CC=C(C=C2C1C)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 32.9, "product": "CC=1NC2=CC=C(C=C2C1C)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
null
null
A suspension of 4-chloro-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline (10 mg, 0.34 mmol), (prepared as described for the starting material in Example 9), and 2,3-dimethyl-5-hydroxyindole (66 mg, 0.41 mmol), (Arch. Pharm. 1972, 305, 159), in DMF (1.5 ml) containing potassium carbonate (70 mg, 0.51 mmol) was heated ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]C1
HCl
CN(C)C=O
100
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1[nH]c2ccc(O)cc2c1C>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCCCN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e83fe1a1497148cb93f5b986bef58f5f
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cc1cc2cc(O)ccc2[nH]1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCc1ccccc1
C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)Cl)OC.OC=1C=C2C=C(NC2=CC1)C>>C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:23]([O:24][CH2:25][c:26]3[cH:27][cH:28][cH:29][cH:30][cH:31]3)[cH:22][c:21]2[n:20][cH:19][n:18]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][c:13]([CH3:14])[cH:15][c:16]2[cH:17]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[cH:15][c:16...
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cc1cc2cc(O)ccc2[nH]1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCc1ccccc1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1ccc(COc2ccc3c(Oc4ccc5[nH]ccc5c4)ncnc3c2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
91.2
[{"value": 91.0, "product": "C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 91.2, "product": "C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 32, 7-benzyloxy-4-chloro-6-methoxyquinazoline (1 g, 3.33 mmol), (prepared as described for the starting material in Example 1), was reacted with 5-hydroxy-2-methylindole (0.59 g, 4 mmol) to give 7-benzyloxy-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (1.25 g,...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.c1ccccc1
HCl
null
null
null
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cc1cc2cc(O)ccc2[nH]1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCc1ccccc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-c969e0ea9f6645219c26c1d9c55db636
COc1ccc2[nH]c(C)cc2c1>>Cc1cc2cc(O)ccc2[nH]1
[OH-].[Na+].B(Br)(Br)Br.COC=1C=C2C=C(NC2=CC1)C.O>>OC=1C=C2C=C(NC2=CC1)C
C[O:7][c:6]1[cH:5][c:4]2[cH:3][c:2]([CH3:1])[nH:11][c:10]2[cH:9][cH:8]1>>[CH3:1][c:2]1[cH:3][c:4]2[cH:5][c:6]([OH:7])[cH:8][cH:9][c:10]2[nH:11]1
COc1ccc2[nH]c(C)cc2c1
Cc1cc2cc(O)ccc2[nH]1
null
null
C(Cl)Cl
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2[nH]ccc2c1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[OH;D1;+0:1]-[c:2](:[c:3]):[c:4]
93
[{"value": 93.0, "product": "OC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 92.9, "product": "OC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
-45
CELSIUS
15
MINUTE
A solution of boron tribromide (32.5 ml, 341 mmol) in methylene choride (60 ml) was added in portions to a solution of 5-methoxy-2-methylindole (25 g, 155 mmol) in methylene chloride (250 ml) cooled at −45° C. After stirring for 15 minutes at −30° C., the mixture was warmed up to ambient temperature and stirred for 1 h...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1ccc2[nH]ccc2c1
Other
C(Cl)Cl
-45
0.25
COc1ccc2[nH]c(C)cc2c1>C(Cl)Cl>Cc1cc2cc(O)ccc2[nH]1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-89f73e14acf541e39c05386c43425075
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCc1ccccc1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O
C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC.[H][H]>>OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC
c1ccc(C[O:24][c:23]2[c:3]([O:2][CH3:1])[cH:4][c:5]3[c:6]([O:7][c:8]4[cH:9][cH:10][c:11]5[nH:12][c:13]([CH3:14])[cH:15][c:16]5[cH:17]4)[n:18][cH:19][n:20][c:21]3[cH:22]2)cc1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[cH:15][c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22]...
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCc1ccccc1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O
null
[Pd]
CN(C)C=O.C(Cl)Cl
Deprotection
Hydroxyl benzyl deprotection
36869d1fe85185a14d9eb30bf05178c600a9b6eca277ffaf3803578c30e0bf5d
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
[#7;a:1]:[c:2]:[c:3]:[c:4](-[O;H0;D2;+0:5]-C-c1:c:c:c:c:c:1):[c:6]>>[#7;a:1]:[c:2]:[c:3]:[c:4](-[OH;D1;+0:5]):[c:6]
89
[{"value": 89.0, "product": "OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 87.1, "product": "OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 7-benzyloxy-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (0.2 g, 0.5 mmol), (prepared as described in Example 48), in a mixture of methylene chloride (5 ml) and DMF (2 ml) containing 10% palladium-on-charcoal (50 mg) was treated with hydrogen at 1.8 atmospheres pressure for 2 hours. The suspension was f...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
c1ccccc1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
Other
[Pd].CN(C)C=O.C(Cl)Cl
null
null
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCc1ccccc1>[Pd].CN(C)C=O.C(Cl)Cl>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-96273fe54ce24254ab4ef9d0098e7fb3
COc1cc2c(Cl)ncnc2cc1OCCCS(C)(=O)=O.Oc1ccc2[nH]c(C(F)(F)F)cc2c1>>COc1cc2c(Oc3ccc4[nH]c(C(F)(F)F)cc4c3)ncnc2cc1OCCCS(C)(=O)=O
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCS(=O)(=O)C.OC=1C=C2C=C(NC2=CC1)C(F)(F)F.C([O-])([O-])=O.[K+].[K+]>>COC=1C=C2C(=NC=NC2=CC1OCCCS(=O)(=O)C)OC=1C=C2C=C(NC2=CC1)C(F)(F)F
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:26]([O:27][CH2:28][CH2:29][CH2:30][S:31]([CH3:32])(=[O:33])=[O:34])[cH:25][c:24]2[n:23][cH:22][n:21]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][c:13]([C:14]([F:15])([F:16])[F:17])[cH:18][c:19]2[cH:20]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:...
COc1cc2c(Cl)ncnc2cc1OCCCS(C)(=O)=O.Oc1ccc2[nH]c(C(F)(F)F)cc2c1
COc1cc2c(Oc3ccc4[nH]c(C(F)(F)F)cc4c3)ncnc2cc1OCCCS(C)(=O)=O
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
87.5
[{"value": 87.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCS(=O)(=O)C)OC=1C=C2C=C(NC2=CC1)C(F)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 87.5, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCS(=O)(=O)C)OC=1C=C2C=C(NC2=CC1)C(F)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
null
null
A suspension of 4-chloro-6-methoxy-7-(3-methylsulphonylpropoxy)quinazoline (150 mg, 0.45 mmol) and 5-hydroxy-2-trifluoromethylindole (109 mg, 0.54 mmol), (prepared as described for the starting material in Example 44), in DMF (1.5 ml) containing potassium carbonate (94 mg, 0.67 mmol) was heated at 100° C. for 1 hour. A...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
HCl
CN(C)C=O
100
null
COc1cc2c(Cl)ncnc2cc1OCCCS(C)(=O)=O.Oc1ccc2[nH]c(C(F)(F)F)cc2c1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C(F)(F)F)cc4c3)ncnc2cc1OCCCS(C)(=O)=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-1ad020d43b3342738f15a32411be44bc
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O.CS(=O)(=O)CCCO>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCS(C)(=O)=O
C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.OC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC.CS(=O)(=O)CCCO.N(=NC(=O)OCC)C(=O)OCC>>COC=1C=C2C(N(C=NC2=CC1OCCCS(=O)(=O)C)COC(C(C)(C)C)=O)=O
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6](=[O:7])[n:8]([CH2:9][O:10][C:11](=[O:12])[C:13]([CH3:14])([CH3:15])[CH3:16])[cH:17][n:18][c:19]2[cH:20][c:21]1[OH:22].O[CH2:23][CH2:24][CH2:25][S:26]([CH3:27])(=[O:28])=[O:29]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6](=[O:7])[n:8]([CH2:9][O:10][C:11](=[O:12])[C:13]([CH3:14])([CH3:15])[CH3...
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O.CS(=O)(=O)CCCO
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCS(C)(=O)=O
null
null
C(Cl)Cl
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
O=c1[nH]cnc2ccccc12
O-[CH2;D2;+0:1]-[C:2]-[C:3].[#7;a:4]:[c:5]:[c:6]:[c:7](-[OH;D1;+0:8]):[c:9]>>[#7;a:4]:[c:5]:[c:6]:[c:7](-[O;H0;D2;+0:8]-[CH2;D2;+0:1]-[C:2]-[C:3]):[c:9]
91
[{"value": 91.0, "product": "COC=1C=C2C(N(C=NC2=CC1OCCCS(=O)(=O)C)COC(C(C)(C)C)=O)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 90.7, "product": "COC=1C=C2C(N(C=NC2=CC1OCCCS(=O)(=O)C)COC(C(C)(C)C)=O)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Triphenylphosphine (8.9 g, 35.2 mmol) was added to a suspension of 7-hydroxy-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (6 g, 19.6 mmol), (prepared as described for the starting material in Example 12), in methylene chloride (150 ml). This was followed by the addition of 3-(methylsulphonyl)-1-propano...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccc2ncncc2c1
HO-
C(Cl)Cl
null
null
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O.CS(=O)(=O)CCCO>C(Cl)Cl>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCS(C)(=O)=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-f76face8e9de472a8b5987c3e4ec04f2
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCS(C)(=O)=O>>COc1cc2c(=O)[nH]cnc2cc1OCCCS(C)(=O)=O
Cl.COC=1C=C2C(N(C=NC2=CC1OCCCS(=O)(=O)C)COC(C(C)(C)C)=O)=O.[OH-].[Na+].CC1=CC=C(C=C1)COC(=O)NNC(=O)C2=NC=CN=C2>>COC=1C=C2C(NC=NC2=CC1OCCCS(=O)(=O)C)=O
CC(C)(C)C(=O)OC[n:8]1[c:6](=[O:7])[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:13]([O:14][CH2:15][CH2:16][CH2:17][S:18]([CH3:19])(=[O:20])=[O:21])[cH:12][c:11]2[n:10][cH:9]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6](=[O:7])[nH:8][cH:9][n:10][c:11]2[cH:12][c:13]1[O:14][CH2:15][CH2:16][CH2:17][S:18]([CH3:19])(=[O:20])=[O:21]
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCS(C)(=O)=O
COc1cc2c(=O)[nH]cnc2cc1OCCCS(C)(=O)=O
null
null
O.CO
Reduction
OtherReaction
9f6991089c15fc054898797f1d3a42b158e517f125611bc103acfc00878b3b20
b8e5da8ea19c403a2e974791a9cf591400749acb6b71151717aaece4f3b22bef
O=c1[nH]cnc2ccccc12
C-C(-C)(-C)-C(=O)-O-C-[n;H0;D3;+0:1]1:[c:2]:[#7;a:3]:[c:4]:[c:5]:[c:6]:1=[O;D1;H0:7]>>[O;D1;H0:7]=[c:6]1:[c:5]:[c:4]:[#7;a:3]:[c:2]:[nH;D2;+0:1]:1
94.2
[{"value": 90.0, "product": "COC=1C=C2C(NC=NC2=CC1OCCCS(=O)(=O)C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 94.2, "product": "COC=1C=C2C(NC=NC2=CC1OCCCS(=O)(=O)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
15
MINUTE
6-Methoxy-7-(3-methylsulphonylpropoxy)-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (7 g, 17 mmol) was suspended in methanol and 2M sodium hydroxide (3.3 ml, 6.6 mmol) was added with continuous stirring. The reaction mixture became homogeneous after 15 minutes. After a further 45 minutes water was added (7 ml) a...
10.6084/m9.figshare.5104873.v1
null
Ester
null
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1
HO-
O.CO
null
0.25
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCS(C)(=O)=O>O.CO>COc1cc2c(=O)[nH]cnc2cc1OCCCS(C)(=O)=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-ccd25b557cf14e1f8fe5ba6a11a356ea
COc1cc2c(=O)[nH]cnc2cc1OCCCS(C)(=O)=O.O=S(Cl)Cl>>COc1cc2c(Cl)ncnc2cc1OCCCS(C)(=O)=O
COC=1C=C2C(NC=NC2=CC1OCCCS(=O)(=O)C)=O.S(=O)(Cl)Cl.C1(=CC=CC=C1)C.C(O)([O-])=O.[Na+].S(=O)(Cl)Cl.CN(C)C=O>>ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCS(=O)(=O)C
O=[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:13]([O:14][CH2:15][CH2:16][CH2:17][S:18]([CH3:19])(=[O:20])=[O:21])[cH:12][c:11]2[n:10][cH:9][nH:8]1.O=S(Cl)[Cl:7]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([Cl:7])[n:8][cH:9][n:10][c:11]2[cH:12][c:13]1[O:14][CH2:15][CH2:16][CH2:17][S:18]([CH3:19])(=[O:20])=[O:21]
COc1cc2c(=O)[nH]cnc2cc1OCCCS(C)(=O)=O.O=S(Cl)Cl
COc1cc2c(Cl)ncnc2cc1OCCCS(C)(=O)=O
null
null
null
Functional Group Interconversion
OtherReaction
3788560e87eee8765e749543914a91a512631307b97fad163ebef894d2a0ea68
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccc2ncncc2c1
Cl-S(=O)-[Cl;H0;D1;+0:1].O=[c;H0;D3;+0:2]1:[nH;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:2]1:[n;H0;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]
88
[{"value": 88.0, "product": "ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCS(=O)(=O)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
6-Methoxy-7-(3-methylsulphonylpropoxy)-3,4-dihydroquinazolin-4-one (3.6 g, 11.5 mmol) was suspended in thionyl chloride (40 ml). DMF (1.8 ml) was added under argon and the mixture was heated at reflux for 1.5 hours. The thionyl chloride was eliminated by several azeotropic distillations using toluene. The solid residue...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1
HCl
null
null
null
COc1cc2c(=O)[nH]cnc2cc1OCCCS(C)(=O)=O.O=S(Cl)Cl>>COc1cc2c(Cl)ncnc2cc1OCCCS(C)(=O)=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e62930fc082348af970119e748626e64
CN(C)CCO.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCN(C)C
C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.N(=NC(=O)OC(C)C)C(=O)OC(C)C.OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC.CN(CCO)C>>CN(C)CCOC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC
O[CH2:25][CH2:26][N:27]([CH3:28])[CH3:29].[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[cH:15][c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[OH:24]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[cH:15][c:16]4[cH:17]3)[n:...
CN(C)CCO.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCN(C)C
null
null
C(Cl)Cl
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
O-[CH2;D2;+0:1]-[C:2]-[#7:3].[#7;a:4]:[c:5]:[c:6]:[c:7](-[OH;D1;+0:8]):[c:9]>>[#7:3]-[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:8]-[c:7](:[c:9]):[c:6]:[c:5]:[#7;a:4]
38
[{"value": 38.0, "product": "CN(C)CCOC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 37.9, "product": "CN(C)CCOC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
0.5M Triphenylphosphine in methylene chloride and diisopropyl azodicarboxylate (150 μl, 0.75 mmol) were added in portions to a suspension of 7-hydroxy-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (112 mg, 0.35 mmol), (prepared as described in Example 49), and N,N-dimethylethanolamine (62 mg, 0.7 mmol) in methylene ch...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
HO-
C(Cl)Cl
null
2
CN(C)CCO.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O>C(Cl)Cl>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCN(C)C
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-cce430dfd4714f8e95b0ff31efa5b976
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Cc1cc2cc(O)ccc2[nH]1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1.OC=1C=C2C=C(NC2=CC1)C.C([O-])([O-])=O.[K+].[K+]>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCCC1)OC=1C=C2C=C(NC2=CC1)C
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:23]([O:24][CH2:25][CH2:26][CH2:27][N:28]3[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]3)[cH:22][c:21]2[n:20][cH:19][n:18]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][c:13]([CH3:14])[cH:15][c:16]2[cH:17]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13](...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Cc1cc2cc(O)ccc2[nH]1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCCCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCCCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
54.8
[{"value": 54.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCCC1)OC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 54.8, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCCC1)OC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
85
CELSIUS
null
null
A solution of 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (100 mg, 0.29 mmol), 5-hydroxy-2-methylindole (53 mg, 0.36 mmol), (prepared as described for the starting material in Example 48), and potassium carbonate (62 mg, 0.44 mmol) in DMF (2 ml) was heated at 85° C. for 3 hours, followed by heating at 95° C. ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
CN(C)C=O
85
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Cc1cc2cc(O)ccc2[nH]1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-1711a3376bc04eb0afdc44598921f85a
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O.OCCCBr>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr
C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.N(=NC(=O)OCC)C(=O)OCC.OC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC.BrCCCO>>BrCCCOC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6](=[O:7])[n:8]([CH2:9][O:10][C:11](=[O:12])[C:13]([CH3:14])([CH3:15])[CH3:16])[cH:17][n:18][c:19]2[cH:20][c:21]1[OH:22].O[CH2:23][CH2:24][CH2:25][Br:26]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6](=[O:7])[n:8]([CH2:9][O:10][C:11](=[O:12])[C:13]([CH3:14])([CH3:15])[CH3:16])[cH:17][n:18][c:19]2...
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O.OCCCBr
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr
null
null
C(Cl)Cl
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
O=c1[nH]cnc2ccccc12
O-[CH2;D2;+0:1]-[C:2]-[C:3].[#7;a:4]:[c:5]:[c:6]:[c:7](-[OH;D1;+0:8]):[c:9]>>[#7;a:4]:[c:5]:[c:6]:[c:7](-[O;H0;D2;+0:8]-[CH2;D2;+0:1]-[C:2]-[C:3]):[c:9]
86.1
[{"value": 86.0, "product": "BrCCCOC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 86.1, "product": "BrCCCOC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
Diethyl azodicarboxylate (3.9 ml, 24.5 mmol) was added in portions to a suspension of 7-hydroxy-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (5 g, 16.3 mmol), (prepared as described for the starting material in Example 12), 3-bromo-1-propanol (2.21 ml, 24.5 mmol) and triphenylphosphine (6.42 g, 24.5 mm...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccc2ncncc2c1
HO-
C(Cl)Cl
null
2
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O.OCCCBr>C(Cl)Cl>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-4d3b8a10f745466aafe4a2248ae64a91
C1CCNCC1.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1
BrCCCOC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC.N1CCCCC1>>COC=1C=C2C(N(C=NC2=CC1OCCCN1CCCCC1)COC(C(C)(C)C)=O)=O
[NH:26]1[CH2:27][CH2:28][CH2:29][CH2:30][CH2:31]1.Br[CH2:25][CH2:24][CH2:23][O:22][c:21]1[c:3]([O:2][CH3:1])[cH:4][c:5]2[c:6](=[O:7])[n:8]([CH2:9][O:10][C:11](=[O:12])[C:13]([CH3:14])([CH3:15])[CH3:16])[cH:17][n:18][c:19]2[cH:20]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6](=[O:7])[n:8]([CH2:9][O:10][C:11](=[O:12])[C:13]([CH3...
C1CCNCC1.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1
null
null
null
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
0240b8450ff2c489d02f5f0d90bc953079d7a3ab239d35a03f26392fc248b4ef
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
O=c1[nH]cnc2cc(OCCCN3CCCCC3)ccc12
Br-[CH2;D2;+0:1]-[C:2]-[C:3].[C:4]-[C:5]-[NH;D2;+0:6]-[C:7]-[C:8]>>[C:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:6](-[C:5]-[C:4])-[C:7]-[C:8]
83
[{"value": 83.0, "product": "COC=1C=C2C(N(C=NC2=CC1OCCCN1CCCCC1)COC(C(C)(C)C)=O)=O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 7-(3-bromopropoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.89 g, 6.78 mmol) in piperidine (100 ml) was heated at 100° C. for 1 hour. After cooling, the volatiles were removed under vacuum. The residue was dissolved in methylene chloride, and washed with saturated ammonium chloride...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1CCNCC1
C1CC[NH]CC1
c1ccc2ncncc2c1.C1CC[NH]CC1
HBr
null
null
null
C1CCNCC1.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-014b8f0e02a14648ba8ac29a10e872a5
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCCCC1
COC=1C=C2C(N(C=NC2=CC1OCCCN1CCCCC1)COC(C(C)(C)C)=O)=O>>COC=1C=C2C(NC=NC2=CC1OCCCN1CCCCC1)=O
CC(C)(C)C(=O)OC[n:8]1[c:6](=[O:7])[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:13]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]3)[cH:12][c:11]2[n:10][cH:9]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6](=[O:7])[nH:8][cH:9][n:10][c:11]2[cH:12][c:13]1[O:14][CH2:15][CH2:16][CH2:17][N:18]1[CH2:19][CH2:20][CH2:...
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1
COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCCCC1
null
null
CO.N
Reduction
OtherReaction
9f6991089c15fc054898797f1d3a42b158e517f125611bc103acfc00878b3b20
b8e5da8ea19c403a2e974791a9cf591400749acb6b71151717aaece4f3b22bef
O=c1[nH]cnc2cc(OCCCN3CCCCC3)ccc12
C-C(-C)(-C)-C(=O)-O-C-[n;H0;D3;+0:1]1:[c:2]:[#7;a:3]:[c:4]:[c:5]:[c:6]:1=[O;D1;H0:7]>>[O;D1;H0:7]=[c:6]1:[c:5]:[c:4]:[#7;a:3]:[c:2]:[nH;D2;+0:1]:1
95.4
[{"value": 95.0, "product": "COC=1C=C2C(NC=NC2=CC1OCCCN1CCCCC1)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 95.4, "product": "COC=1C=C2C(NC=NC2=CC1OCCCN1CCCCC1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 6-methoxy-7-(3-piperidinopropoxy)-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.35 g, 5.45 mmol) in 7M ammonia in methanol (50 ml) was stirred overnight at ambient temperature. The volatiles were removed under vacuum and the residue was triturated with ether, filtered and washed with ether follow...
10.6084/m9.figshare.5104873.v1
null
Ester
null
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1CC[NH]CC1
HO-
CO.N
null
null
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCCCC1>CO.N>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-8d897344702e4688b939d67c1d01d492
COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCCCC1.O=S(Cl)Cl>>COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1
COC=1C=C2C(NC=NC2=CC1OCCCN1CCCCC1)=O.CN(C)C=O.S(=O)(Cl)Cl>>ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1
O=[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:13]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]3)[cH:12][c:11]2[n:10][cH:9][nH:8]1.O=S(Cl)[Cl:7]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([Cl:7])[n:8][cH:9][n:10][c:11]2[cH:12][c:13]1[O:14][CH2:15][CH2:16][CH2:17][N:18]1[CH2:19][CH2:20][CH2:21][CH2...
COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCCCC1.O=S(Cl)Cl
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1
null
null
null
Functional Group Interconversion
OtherReaction
3788560e87eee8765e749543914a91a512631307b97fad163ebef894d2a0ea68
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ncc2ccc(OCCCN3CCCCC3)cc2n1
Cl-S(=O)-[Cl;H0;D1;+0:1].O=[c;H0;D3;+0:2]1:[nH;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:2]1:[n;H0;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]
76
[{"value": 76.0, "product": "ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 6-methoxy-7-(3-piperidinopropoxy)-3,4-dihydroquinazolin-4-one (1.5 g, 4.7 mmol) in thionyl chloride (15 ml) containing DMF (1.5 ml) was heated at reflux for 3 hours. After cooling, the volatiles were removed under vacuum. The residue was azeotroped with toluene. The solid was partitioned between methylene...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
null
null
null
COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCCCC1.O=S(Cl)Cl>>COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a248418fe27d4b758d9ad8eaa7e43814
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1ccc2[nH]ccc2c1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCCCN1CCCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1.OC=1C=C2C=CNC2=CC1>>N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:22]([O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]3)[cH:21][c:20]2[n:19][cH:18][n:17]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][cH:13][cH:14][c:15]2[cH:16]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][cH:13][cH:14][c...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1ccc2[nH]ccc2c1
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCCCN1CCCCC1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCCCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
442.6
[{"value": 45.0, "product": "N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 442.6, "product": "N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 67, 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (10 mg), (prepared as described for the starting material in Example 67), was reacted with 5-hydroxyindole (48 mg, 0.36 mmol) to give 4-(indol-5-yloxy)-6-methoxy-7-(3-piperidinopropoxy)quinazoline (57 mg,...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
null
null
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1ccc2[nH]ccc2c1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCCCN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b096573f55bf4a47bccdbc6229d71106
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)OCC2CCN(C(=O)OC(C)(C)C)CC2)cc1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCN(C(=O)OC(C)(C)C)CC1
O.OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC.CC1=CC=C(C=C1)S(=O)(=O)OCC1CCN(CC1)C(=O)OC(C)(C)C.C([O-])([O-])=O.[K+].[K+]>>COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C(=O)OC(C)(C)C)OC=1C=C2C=C(NC2=CC1)C
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[cH:15][c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[OH:24].Cc1ccc(S(=O)(=O)O[CH2:25][CH:26]2[CH2:27][CH2:28][N:29]([C:30](=[O:31])[O:32][C:33]([CH3:34])([CH3:35])[CH3:36])[CH2:37][CH2:38]2)cc1>>[CH3:1][O:2][c:3]1[cH:4]...
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)OCC2CCN(C(=O)OC(C)(C)C)CC2)cc1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCN(C(=O)OC(C)(C)C)CC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
b5213736859cf91483a02f350869986d9b7674724716adef8a5d7a4bbdb79574
3d107e624e135e10014c7bf413dd0be27e1e4488f039e545b94cb1680b764158
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCC3CCNCC3)cc2n1
C-c1:c:c:c(-S(=O)(=O)-O-[CH2;D2;+0:1]-[C:2](-[C:3])-[C:4]):c:c:1.[#7;a:5]:[c:6]:[c:7]:[c:8](-[OH;D1;+0:9]):[c:10]>>[#7;a:5]:[c:6]:[c:7]:[c:8](-[O;H0;D2;+0:9]-[CH2;D2;+0:1]-[C:2](-[C:3])-[C:4]):[c:10]
77.1
[{"value": 77.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C(=O)OC(C)(C)C)OC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 77.1, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C(=O)OC(C)(C)C)OC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
null
null
A solution of 7-hydroxy-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (161 mg, 0.5 mmol), (prepared as described in Example 49), 4-(4-methylphenylsulphonyloxymethyl)-1-tert-butoxycarbonylpiperidine (222 mg, 0.6 mmol), (prepared as described for the starting material in Example 10), and potassium carbonate (188 mg, 1 m...
10.6084/m9.figshare.5104873.v1
null
Tosylate.Aromatic alcohol
Ether
c1ccccc1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
TsOH.HO-
CN(C)C=O
100
null
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)OCC2CCN(C(=O)OC(C)(C)C)CC2)cc1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCN(C(=O)OC(C)(C)C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-217d5f891d1e4cc6b69362dc24ec7253
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCN(C(=O)OC(C)(C)C)CC1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCNCC1
COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C(=O)OC(C)(C)C)OC=1C=C2C=C(NC2=CC1)C.C(=O)(C(F)(F)F)O>>COC=1C=C2C(=NC=NC2=CC1OCC1CCNCC1)OC=1C=C2C=C(NC2=CC1)C
CC(C)(C)OC(=O)[N:29]1[CH2:28][CH2:27][CH:26]([CH2:25][O:24][c:23]2[c:3]([O:2][CH3:1])[cH:4][c:5]3[c:6]([O:7][c:8]4[cH:9][cH:10][c:11]5[nH:12][c:13]([CH3:14])[cH:15][c:16]5[cH:17]4)[n:18][cH:19][n:20][c:21]3[cH:22]2)[CH2:31][CH2:30]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:...
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCN(C(=O)OC(C)(C)C)CC1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCNCC1
null
null
C(Cl)Cl
Reduction
Boc amine deprotection
bf3cd5dc3e17e694d8665c89f5d7e08e8763b18436a633eb66e9bf530b8b0316
a94b29c7264c852156fc1cdd4a0951a4fc26c06d0edc9e50c743825dbf79e3fd
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCC3CCNCC3)cc2n1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1](-[C:2]-[C:3])-[C:4]-[C:5]>>[C:3]-[C:2]-[NH;D2;+0:1]-[C:4]-[C:5]
96
[{"value": 96.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCNCC1)OC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 95.6, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCNCC1)OC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
A solution of 6-methoxy-4-(2-methylindol-5-yloxy)-7-(1-tert-butoxycarbonylpiperidin-4-ylmethoxy)quinazoline (155 mg, 0.3 mmol), (prepared as described in Example 69), in methylene chloride (5 ml) containing TFA (1 ml) was stirred at ambient temperature for 30 minutes. The volatiles were removed under vacuum and the res...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
C1CC[NH]CC1
C1CCNCC1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CCNCC1
HO-
C(Cl)Cl
null
0.5
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCN(C(=O)OC(C)(C)C)CC1>C(Cl)Cl>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCNCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-da3ae70f1ddc41818b8f4183bc0df9a3
COCC=O.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCNCC1>>COCCN1CCC(COc2cc3ncnc(Oc4ccc5[nH]c(C)cc5c4)c3cc2OC)CC1
C(O)([O-])=O.[Na+].COCC=O.C(C)(=O)O[BH-](OC(C)=O)OC(C)=O.[Na+].COC=1C=C2C(=NC=NC2=CC1OCC1CCNCC1)OC=1C=C2C=C(NC2=CC1)C>>COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)CCOC)OC=1C=C2C=C(NC2=CC1)C
O=[CH:4][CH2:3][O:2][CH3:1].[NH:5]1[CH2:6][CH2:7][CH:8]([CH2:9][O:10][c:11]2[cH:12][c:13]3[n:14][cH:15][n:16][c:17]([O:18][c:19]4[cH:20][cH:21][c:22]5[nH:23][c:24]([CH3:25])[cH:26][c:27]5[cH:28]4)[c:29]3[cH:30][c:31]2[O:32][CH3:33])[CH2:34][CH2:35]1>>[CH3:1][O:2][CH2:3][CH2:4][N:5]1[CH2:6][CH2:7][CH:8]([CH2:9][O:10][c:...
COCC=O.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCNCC1
COCCN1CCC(COc2cc3ncnc(Oc4ccc5[nH]c(C)cc5c4)c3cc2OC)CC1
null
null
CO.C(Cl)Cl
Heteroatom Alkylation and Arylation
reductive amination
d0e659bc8d1e29e09a61320b4c537e66ad57335a51368c8bd48de9bdffa59372
2d03f38884b1fbb0c0d6e6f2de31afb25102fec87f347c3a123e064c1bfef0ad
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCC3CCNCC3)cc2n1
O=[CH;D2;+0:1]-[C:2]-[#8:3].[C:4]-[C:5]-[NH;D2;+0:6]-[C:7]-[C:8]>>[#8:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:6](-[C:5]-[C:4])-[C:7]-[C:8]
47.3
[{"value": 47.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)CCOC)OC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 47.3, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)CCOC)OC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1.5
HOUR
Methoxyacetaldehyde (368 mg, 3.47 mmol) (freshly distilled) followed by sodium triacetoxyborohydride (552 mg, 2.6 mol) were added to a solution of 6-methoxy-4-(2-methylindol-5-yloxy)-7-(piperidin-4-ylmethoxy)quinazoline (726 mg, 1.74 mmol), (prepared as described in Example 70), in a mixture of methylene chloride (15 m...
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Secondary amine
Tertiary amine
C1CCNCC1
C1CC[NH]CC1
C1CC[NH]CC1.c1ccc2ncncc2c1.c1ccc2[nH]ccc2c1
Other
CO.C(Cl)Cl
null
1.5
COCC=O.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCNCC1>CO.C(Cl)Cl>COCCN1CCC(COc2cc3ncnc(Oc4ccc5[nH]c(C)cc5c4)c3cc2OC)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-7541a0616eea4860b1a30bd7bd123fbd
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1O.O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F>>COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1OS(=O)(=O)C(F)(F)F
FC(S(=O)(=O)OS(=O)(=O)C(F)(F)F)(F)F.ClC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)O)C=C1)F.N1=CC=CC=C1>>ClC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)OS(=O)(=O)C(F)(F)F)C=C1)F
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]([Cl:12])[cH:13][c:14]3[F:15])[n:16][cH:17][n:18][c:19]2[cH:20][c:21]1[OH:22].O=S(=O)(O[S:23](=[O:24])(=[O:25])[C:26]([F:27])([F:28])[F:29])C(F)(F)F>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]([Cl:12])[cH:13][c:14]3[F:15])[n:16][c...
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1O.O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1OS(=O)(=O)C(F)(F)F
null
null
C(Cl)Cl
Functional Group Interconversion
Alcohol to triflate conversion
934d625c86d5da305dd43240eee33b5e46f4d298c87ccdc218e9e2eb60c650b5
13e8f5cec02bd6a2d12ae535029c405c270682596231c5c8422ac50b2cb1ec74
c1ccc(Oc2ncnc3ccccc23)cc1
F-C(-F)(-F)-S(=O)(=O)-O-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[C:4](-[F;D1;H0:5])(-[F;D1;H0:6])-[F;D1;H0:7].[#7;a:8]:[c:9]:[c:10]:[c:11](-[OH;D1;+0:12]):[c:13]>>[#7;a:8]:[c:9]:[c:10]:[c:11](-[O;H0;D2;+0:12]-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[C:4](-[F;D1;H0:5])(-[F;D1;H0:6])-[F;D1;H0:7]):[c:13]
88.5
[{"value": 88.0, "product": "ClC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)OS(=O)(=O)C(F)(F)F)C=C1)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 88.5, "product": "ClC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)OS(=O)(=O)C(F)(F)F)C=C1)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
5
CELSIUS
1
HOUR
Trifluoromethanesulphonic anhydride (338 mg, 1.2 mmol) was added to a suspension of 4-(4-chloro-2-fluorophenoxy)-7-hydroxy-6-methoxyquinazoline (320 mg, I mmol), (prepared as described for the starting material in Example 5), in methylene chloride (2 ml) containing pyridine (2 ml) cooled at 5° C. When the addition was ...
10.6084/m9.figshare.5104873.v1
null
Triflate.Triflate.Aromatic alcohol
Triflate
null
null
c1ccccc1.c1ccc2ncncc2c1
HF
C(Cl)Cl
5
1
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1O.O=S(=O)(OS(=O)(=O)C(F)(F)F)C(F)(F)F>C(Cl)Cl>COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1OS(=O)(=O)C(F)(F)F
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-53240fd6758b45f5a0295e2790b9229e
C=CC(=O)OC(C)(C)C.COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1OS(=O)(=O)C(F)(F)F>>COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1C=CC(=O)OC(C)(C)C
C(C)N(CC)CC.C(C=C)(=O)OC(C)(C)C.ClC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)OS(=O)(=O)C(F)(F)F)C=C1)F.C1(=CC=CC=C1)C(CCP)C1=CC=CC=C1>>ClC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)C=CC(=O)OC(C)(C)C)C=C1)F
[CH2:22]=[CH:23][C:24](=[O:25])[O:26][C:27]([CH3:28])([CH3:29])[CH3:30].O=S(=O)(O[c:21]1[c:3]([O:2][CH3:1])[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]([Cl:12])[cH:13][c:14]3[F:15])[n:16][cH:17][n:18][c:19]2[cH:20]1)C(F)(F)F>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]([Cl:12])[cH:13][c:14]3[...
C=CC(=O)OC(C)(C)C.COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1OS(=O)(=O)C(F)(F)F
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1C=CC(=O)OC(C)(C)C
null
C(C)(=O)[O-].[Pd+2].C(C)(=O)[O-]
CN(C)C=O
C-C Coupling
OtherReaction
7100118f57cdacf6652618e075fd189ecc51663a50ff9d5c87cbfd490068fb24
e84d2ff35b106b73e905407d80ffdd5c53fba81bdf3725d58511290daa9d3d79
c1ccc(Oc2ncnc3ccccc23)cc1
F-C(-F)(-F)-S(=O)(=O)-O-[c;H0;D3;+0:1]1:[c:2]:[c:3]2:[#7;a:4]:[c:5]:[#7;a:6]:[c:7]:[c:8]:2:[c:9]:[c:10]:1-[#8:11].[C;D1;H3:12]-[C:13](-[C;D1;H3:14])(-[C;D1;H3:15])-[#8:16]-[C:17](=[O;D1;H0:18])-[C:19]=[CH2;D1;+0:20]>>[#8:11]-[c:10]1:[c:9]:[c:8]2:[c:7]:[#7;a:6]:[c:5]:[#7;a:4]:[c:3]:2:[c:2]:[c;H0;D3;+0:1]:1-[CH;D2;+0:20]...
49
[{"value": 49.0, "product": "ClC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)C=CC(=O)OC(C)(C)C)C=C1)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 48.7, "product": "ClC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)C=CC(=O)OC(C)(C)C)C=C1)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
6
HOUR
Triethylamine (33 mg, 0.33 mmol) and tert-butyl acrylate (77 mg, 0.6 mmol) followed by diphenylpropylphosphine (3.4 mg, 0.008 mmol) and palladium(II) acetate (1.7 mg, 0.0075 mmol) were added to a solution of 4-(4-chloro-2-fluorophenoxy)-6-methoxy-7-(trifluoromethylsulphonyloxy)quinazoline (136 mg, 0.3 mmol) in DMF (1.5...
10.6084/m9.figshare.5104873.v1
null
Triflate.Vinyl
null
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccccc1.c1ccc2ncncc2c1
TfOH.HO-
C(C)(=O)[O-].[Pd+2].C(C)(=O)[O-].CN(C)C=O
null
6
C=CC(=O)OC(C)(C)C.COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1OS(=O)(=O)C(F)(F)F>C(C)(=O)[O-].[Pd+2].C(C)(=O)[O-].CN(C)C=O>COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1C=CC(=O)OC(C)(C)C
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-023fa086034942b6ba1d3852ed3912fe
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1C=CC(=O)OC(C)(C)C>>COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1C=CC(=O)O
ClC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)C=CC(=O)OC(C)(C)C)C=C1)F>>C(=O)(O)C=CC1=C(C=C2C(=NC=NC2=C1)OC1=C(C=C(C=C1)Cl)F)OC
CC(C)(C)[O:26][C:24]([CH:23]=[CH:22][c:21]1[c:3]([O:2][CH3:1])[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]([Cl:12])[cH:13][c:14]3[F:15])[n:16][cH:17][n:18][c:19]2[cH:20]1)=[O:25]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]([Cl:12])[cH:13][c:14]3[F:15])[n:16][cH:17][n:18][c:19]2[cH:20][c:21]1...
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1C=CC(=O)OC(C)(C)C
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1C=CC(=O)O
null
null
C(Cl)Cl.C(=O)(C(F)(F)F)O
Deprotection
Deprotection of carboxylic acid
152e5537e48c95b4a3e767536b0f9f68d1308e5f484070828ab5ed951805157a
7f019d4cfe9b3036d0a2d3a3209aa0e1fcb05418ebee15a4be5e125d315d5f01
c1ccc(Oc2ncnc3ccccc23)cc1
C-C(-C)(-C)-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[C:4]=[C:5]-[c:6]>>[O;D1;H0:3]=[C:2](-[OH;D1;+0:1])-[C:4]=[C:5]-[c:6]
87.6
[{"value": 85.0, "product": "C(=O)(O)C=CC1=C(C=C2C(=NC=NC2=C1)OC1=C(C=C(C=C1)Cl)F)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 87.6, "product": "C(=O)(O)C=CC1=C(C=C2C(=NC=NC2=C1)OC1=C(C=C(C=C1)Cl)F)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1.5
HOUR
A solution of 4-(4-chloro-2-fluorophenoxy)-6-methoxy-7-(2-(tert-butoxycarbonyl)vinyl)quinazoline (581 mg, 1.31 mmol) in a mixture of methylene chloride/TFA (2.5 ml/2.5 ml) was stirred at ambient temperature for 1.5 hours. After removal of the volatiles under vacuum, the residue was partitioned between ethyl acetate and...
10.6084/m9.figshare.5104873.v1
null
Ester.Boc
Carboxylic acid
null
null
c1ccccc1.c1ccc2ncncc2c1
Other
C(Cl)Cl.C(=O)(C(F)(F)F)O
null
1.5
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1C=CC(=O)OC(C)(C)C>C(Cl)Cl.C(=O)(C(F)(F)F)O>COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1C=CC(=O)O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-c762e8e8205e40a5b0790bfd72e40a24
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1C=CC(=O)O.Cc1cc2cc(O)ccc2[nH]1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1C=CC(=O)O
[Na].C[Si](C)(C)N[Si](C)(C)C.C1CCOC1.C(=O)(O)C=CC1=C(C=C2C(=NC=NC2=C1)OC1=C(C=C(C=C1)Cl)F)OC.OC=1C=C2C=C(NC2=CC1)C>>C(=O)(O)C=CC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC
Fc1cc(Cl)ccc1O[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:23]([CH:24]=[CH:25][C:26](=[O:27])[OH:28])[cH:22][c:21]2[n:20][cH:19][n:18]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][c:13]([CH3:14])[cH:15][c:16]2[cH:17]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[cH:15][c:16]4[cH:17...
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1C=CC(=O)O.Cc1cc2cc(O)ccc2[nH]1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1C=CC(=O)O
null
null
CS(=O)C
Heteroatom Alkylation and Arylation
OtherReaction
2cfaf3a86d100b1ba78e674d1577e6d6c1e9e8fd22a03032330781c71fecde7c
123a439cc2c8832d15eb655ab85a8be8bc914ef22c53e79f644ec1c9eb4c6b12
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
Cl-c1:c:c:c(-O-[c;H0;D3;+0:1]2:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:2:[c:8]):c(-F):c:1.[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
71.4
[{"value": 71.0, "product": "C(=O)(O)C=CC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 71.4, "product": "C(=O)(O)C=CC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
1M Sodium HMDS in THF (0.84 ml, 8.4 mmol) was added to a suspension of 7-(2-carboxyvinyl)-4-(4-chloro-2-fluorophenoxy)-6-methoxyquinazoline (105 mg, 0.28 mmol) and 5-hydroxy-2methylindole (82 mg, 0.56 mmol), (prepared as described for the starting material in Example 48), in DMSO (1.5 ml). After stirring for 2 hours at...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Ether.Aromatic alcohol
Ether
c1ccccc1.c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
HF
CS(=O)C
null
2
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1C=CC(=O)O.Cc1cc2cc(O)ccc2[nH]1>CS(=O)C>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1C=CC(=O)O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-28efbc76097047bc91374bc3ed11bac3
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.ClCCCBr>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCCl
O.OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC.BrCCCCl.C([O-])([O-])=O.[K+].[K+]>>ClCCCOC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[cH:15][c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[OH:24].Br[CH2:25][CH2:26][CH2:27][Cl:28]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[cH:15][c:16]4[cH:17]3)[n:18][cH:1...
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.ClCCCBr
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCCl
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
Br-[CH2;D2;+0:1]-[C:2]-[C:3].[#7;a:4]:[c:5]:[c:6]:[c:7](-[OH;D1;+0:8]):[c:9]>>[#7;a:4]:[c:5]:[c:6]:[c:7](-[O;H0;D2;+0:8]-[CH2;D2;+0:1]-[C:2]-[C:3]):[c:9]
70.4
[{"value": 70.0, "product": "ClCCCOC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 70.4, "product": "ClCCCOC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
A suspension of 7-hydroxy-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (321 mg, 1 mmol), (prepared as described in Example 49), 1-bromo-3-chloropropane (120 μl, 1.2 mmol) and potassium carbonate (359 mg, 2.6 mmol) in DMF (5 ml) was stirred at ambient temperature overnight. After addition of water, the precipitate was...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
HBr
CN(C)C=O
null
8
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.ClCCCBr>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCCl
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-2b20ed060b2a4669a6217d9c0f6a18c1
CN1CCNCC1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCCl>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCN(C)CC1
ClCCCOC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC.CN1CCNCC1>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCN(CC1)C)OC=1C=C2C=C(NC2=CC1)C
[NH:28]1[CH2:29][CH2:30][N:31]([CH3:32])[CH2:33][CH2:34]1.Cl[CH2:27][CH2:26][CH2:25][O:24][c:23]1[c:3]([O:2][CH3:1])[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[cH:15][c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12...
CN1CCNCC1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCCl
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCN(C)CC1
null
null
null
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
bad6b7d8e43c3debef0c262d60564e43415b41bcee72e526419c8c16be18fec1
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCNCC3)cc2n1
Cl-[CH2;D2;+0:1]-[C:2]-[C:3].[#7:4]1-[C:5]-[C:6]-[NH;D2;+0:7]-[C:8]-[C:9]-1>>[C:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:7]1-[C:6]-[C:5]-[#7:4]-[C:9]-[C:8]-1
32
[{"value": 32.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCN(CC1)C)OC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 7-(3-chloropropoxy)-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (150 mg, 0.38 mmol), (prepared as described in Example 73), in 1-methylpiperazine (2 ml) was heated at 100° C. for 2 hours. After cooling, the mixture was partitioned between ethyl acetate and aqueous 5% sodium hydrogen carbonate. The orga...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1CNCC[NH]1
C1C[NH]CC[NH]1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1C[NH]CC[NH]1
HCl
null
null
null
CN1CCNCC1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCCl>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3ee680b06e7f4affbf1c69d8a63a3d10
CCN(CC)CCO.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O>>CCN(CC)CCOc1cc2ncnc(Oc3ccc4[nH]c(C)cc4c3)c2cc1OC
N(=NC(=O)OCC)C(=O)OCC.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C(C)N(CCO)CC.OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC>>C(C)N(CC)CCOC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC
O[CH2:7][CH2:6][N:3]([CH2:2][CH3:1])[CH2:4][CH3:5].[OH:8][c:9]1[cH:10][c:11]2[n:12][cH:13][n:14][c:15]([O:16][c:17]3[cH:18][cH:19][c:20]4[nH:21][c:22]([CH3:23])[cH:24][c:25]4[cH:26]3)[c:27]2[cH:28][c:29]1[O:30][CH3:31]>>[CH3:1][CH2:2][N:3]([CH2:4][CH3:5])[CH2:6][CH2:7][O:8][c:9]1[cH:10][c:11]2[n:12][cH:13][n:14][c:15](...
CCN(CC)CCO.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O
CCN(CC)CCOc1cc2ncnc(Oc3ccc4[nH]c(C)cc4c3)c2cc1OC
null
null
C(Cl)Cl
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
O-[CH2;D2;+0:1]-[C:2]-[#7:3].[#7;a:4]:[c:5]:[c:6]:[c:7](-[OH;D1;+0:8]):[c:9]>>[#7:3]-[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:8]-[c:7](:[c:9]):[c:6]:[c:5]:[#7;a:4]
70
[{"value": 70.0, "product": "C(C)N(CC)CCOC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 69.9, "product": "C(C)N(CC)CCOC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
Triphenylphosphine (262 mg, 1 mmol) and N,N-diethylethanolamine (88 mg, 0.75 mmol) were added to a suspension of 7-hydroxy-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (160 mg, 0.5 mmol), (prepared as described in Example 49), in methylene chloride (5 ml), followed by the addition, in portions, of diethyl azodicarbox...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccc2ncncc2c1.c1ccc2[nH]ccc2c1
HO-
C(Cl)Cl
null
1
CCN(CC)CCO.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O>C(Cl)Cl>CCN(CC)CCOc1cc2ncnc(Oc3ccc4[nH]c(C)cc4c3)c2cc1OC
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-dc971279b9e240d087147068c0457939
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.OCCOc1ccncc1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCOc1ccncc1
OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC.OCCOC1=CC=NC=C1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.N(=NC(=O)OC(C)C)C(=O)OC(C)C>>COC=1C=C2C(=NC=NC2=CC1OCCOC1=CC=NC=C1)OC=1C=C2C=C(NC2=CC1)C
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[cH:15][c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[OH:24].O[CH2:25][CH2:26][O:27][c:28]1[cH:29][cH:30][n:31][cH:32][cH:33]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[c...
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.OCCOc1ccncc1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCOc1ccncc1
null
null
C(Cl)Cl
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1cc(OCCOc2ccc3c(Oc4ccc5[nH]ccc5c4)ncnc3c2)ccn1
O-[CH2;D2;+0:1]-[C:2]-[#8:3].[#7;a:4]:[c:5]:[c:6]:[c:7](-[OH;D1;+0:8]):[c:9]>>[#7;a:4]:[c:5]:[c:6]:[c:7](-[O;H0;D2;+0:8]-[CH2;D2;+0:1]-[C:2]-[#8:3]):[c:9]
54
[{"value": 54.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCOC1=CC=NC=C1)OC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 53.5, "product": "COC=1C=C2C(=NC=NC2=CC1OCCOC1=CC=NC=C1)OC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
A solution of 7-hydroxy-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (193 mg, 0.6 mmol), (prepared as described in Example 49), 4-(2-hydroxyethoxy)pyridine (166 mg, 1.2 mmol), (J. Chem. Soc. Perkin II, 1987, 1867), in methylene chloride (5 ml) containing triphenylphosphine (330 mg, 1.26 mmol) and diisopropyl azodicar...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.c1ccncc1
HO-
C(Cl)Cl
null
2
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.OCCOc1ccncc1>C(Cl)Cl>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCOc1ccncc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-82407654665140cd8ab19b027a2616a6
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCN(C)C(=O)OC(C)(C)C.CS(=O)(=O)Cl>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCN(C)S(C)(=O)=O
CS(=O)(=O)Cl.C(=O)(C(F)(F)F)O.COC=1C=C2C(=NC=NC2=CC1OCCN(C(=O)OC(C)(C)C)C)OC=1C=C2C=C(NC2=CC1)C.C(C)N(CC)CC>>COC=1C=C2C(=NC=NC2=CC1OCCN(S(=O)(=O)C)C)OC=1C=C2C=C(NC2=CC1)C
CC(C)(C)OC(=O)[N:27]([CH2:26][CH2:25][O:24][c:23]1[c:3]([O:2][CH3:1])[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[cH:15][c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22]1)[CH3:28].Cl[S:29]([CH3:30])(=[O:31])=[O:32]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c...
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCN(C)C(=O)OC(C)(C)C.CS(=O)(=O)Cl
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCN(C)S(C)(=O)=O
null
null
C(Cl)Cl
Acylation
OtherReaction
2b1ae4c17a0a628d4c79000b5e250235a52882f8aea5522afb71b80acc2e8f07
705725ff5b1b5bdebe12db390e8895152ae89941b9a07e00716e981f5b25c654
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1](-[C;D1;H3:2])-[C:3]-[C:4].Cl-[S;H0;D4;+0:5](-[C;D1;H3:6])(=[O;D1;H0:7])=[O;D1;H0:8]>>[C:4]-[C:3]-[N;H0;D3;+0:1](-[C;D1;H3:2])-[S;H0;D4;+0:5](-[C;D1;H3:6])(=[O;D1;H0:7])=[O;D1;H0:8]
38.2
[{"value": 38.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCN(S(=O)(=O)C)C)OC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 38.2, "product": "COC=1C=C2C(=NC=NC2=CC1OCCN(S(=O)(=O)C)C)OC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
A suspension of 6-methoxy-4-(2-methylindol-5-yloxy)-7-(2-(N-methyl-N-tert-butoxycarbonylamino)ethoxy)quinazoline (148 mg, 0.31 mmol), (prepared as described in Example 149), in methylene chloride (4 ml) containing TFA (1 ml) was stirred for 1 hour. After removing the volatiles under vacuum, the residue was azeotroped w...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Sulfonyl halide.Boc
Tertiary amine
null
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
HCl
C(Cl)Cl
null
1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCN(C)C(=O)OC(C)(C)C.CS(=O)(=O)Cl>C(Cl)Cl>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCN(C)S(C)(=O)=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a03dd6dfa1f14dcb9f0a84e8b45e70aa
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCOC1CCNCC1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCOC1CCN(CCC#N)CC1
COC=1C=C2C(=NC=NC2=CC1OCCOC1CCNCC1)OC=1C=C2C=C(NC2=CC1)C>>C(#N)CCN1CCC(CC1)OCCOC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[cH:15][c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[O:24][CH2:25][CH2:26][O:27][CH:28]1[CH2:29][CH2:32][NH:31][CH2:36][CH2:37]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14]...
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCOC1CCNCC1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCOC1CCN(CCC#N)CC1
null
null
C(C=C)#N.CO.C(Cl)Cl
Miscellaneous
OtherReaction
a7099ea97bc43b09bfde1675aaf7ec66651498d865ae483e4bd4d037e726db38
78ae9872e848ed8994acd80eff3ed9e4541fcd281499500b75914b57d1abfbba
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCOC3CCNCC3)cc2n1
[#8:1]-[C:2]1-[C:3]-[C:4]-[NH;D2;+0:5]-[CH2;D2;+0:6]-[CH2;D2;+0:7]-1>>[#8:1]-[C:2]1-[C:3]-[C:4]-[N;H0;D3;+0:5](-[CH2;D2;+0:6]-[C:8]-[C:9])-[C:10]-[CH2;D2;+0:7]-1
171.2
[{"value": 86.0, "product": "C(#N)CCN1CCC(CC1)OCCOC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 171.2, "product": "C(#N)CCN1CCC(CC1)OCCOC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 6-methoxy-4-(2-methylindol-5-yloxy)-7-(2-(piperidin-4-yloxy)ethoxy)quinazoline (76 mg, 0.17 mmol), (prepared as described in Example 77), in acrylonitrile (0.5 ml), methylene chloride (1 ml) and methanol (1 ml) was stirred overnight at ambient temperature. After removal of the volatiles under vacuum the r...
10.6084/m9.figshare.5104873.v1
null
Secondary amine
Nitrile.Tertiary amine
C1CCNCC1
C1CC[NH]CC1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
Other
C(C=C)#N.CO.C(Cl)Cl
null
null
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCOC1CCNCC1>C(C=C)#N.CO.C(Cl)Cl>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCOC1CCN(CCC#N)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-626a831be92641a784c20f02906b08b3
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1ccc2cc[nH]c2c1>>COc1cc2c(Oc3ccc4cc[nH]c4c3)ncnc2cc1OCCCN1CCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1.OC1=CC=C2C=CNC2=C1.C([O-])([O-])=O.[K+].[K+]>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCC1)OC1=CC=C2C=CNC2=C1
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:22]([O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][CH2:30][CH2:31]3)[cH:21][c:20]2[n:19][cH:18][n:17]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[cH:12][cH:13][nH:14][c:15]2[cH:16]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[cH:12][cH:13][nH:14][c:15]4[cH...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1ccc2cc[nH]c2c1
COc1cc2c(Oc3ccc4cc[nH]c4c3)ncnc2cc1OCCCN1CCCC1
null
null
C(Cl)Cl.CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3cc[nH]c3c2)c2ccc(OCCCN3CCCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#7;a:9]:[c:10]:[c:11]:[c:12](-[OH;D1;+0:13]):[c:14]>>[#7;a:9]:[c:10]:[c:11]:[c:12](-[O;H0;D2;+0:13]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:14]
69.4
[{"value": 69.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCC1)OC1=CC=C2C=CNC2=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 69.4, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCC1)OC1=CC=C2C=CNC2=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
95
CELSIUS
null
null
A solution of 4-chloro-6-methoxy-7-(3-pyrrolidin-1-ylpropoxy)quinazoline (100 m g, 0.31 mmol), (prepared as described for the starting material in Example 9), 6-hydroxyindole (50 mg, 0.37 mmol) and potassium carbonate (64 mg, 0.466 mmol) in DMF (1 ml) was heated at 95° C. for 4 hours. After cooling, the mixture was dil...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]C1
HCl
C(Cl)Cl.CN(C)C=O
95
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1ccc2cc[nH]c2c1>C(Cl)Cl.CN(C)C=O>COc1cc2c(Oc3ccc4cc[nH]c4c3)ncnc2cc1OCCCN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-dc11ca25b1654c81a392193d4382e978
Cc1cc2cc(Oc3ncnc4cc(O)ccc34)ccc2[nH]1.OCCCN1CCCC1>>Cc1cc2cc(Oc3ncnc4cc(OCCCN5CCCC5)ccc34)ccc2[nH]1
N(=NC(=O)OC(C)C)C(=O)OC(C)C.OC1=CC=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.N1(CCCC1)CCCO>>CC=1NC2=CC=C(C=C2C1)OC1=NC=NC2=CC(=CC=C12)OCCCN1CCCC1
[CH3:1][c:2]1[cH:3][c:4]2[cH:5][c:6]([O:7][c:8]3[n:9][cH:10][n:11][c:12]4[cH:13][c:14]([OH:15])[cH:24][cH:25][c:26]34)[cH:27][cH:28][c:29]2[nH:30]1.O[CH2:16][CH2:17][CH2:18][N:19]1[CH2:20][CH2:21][CH2:22][CH2:23]1>>[CH3:1][c:2]1[cH:3][c:4]2[cH:5][c:6]([O:7][c:8]3[n:9][cH:10][n:11][c:12]4[cH:13][c:14]([O:15][CH2:16][CH2...
Cc1cc2cc(Oc3ncnc4cc(O)ccc34)ccc2[nH]1.OCCCN1CCCC1
Cc1cc2cc(Oc3ncnc4cc(OCCCN5CCCC5)ccc34)ccc2[nH]1
null
null
C(Cl)Cl
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCCC3)cc2n1
O-[CH2;D2;+0:1]-[C:2]-[C:3].[#7;a:4]:[c:5]:[c:6]:[c:7](-[OH;D1;+0:8]):[c:9]>>[#7;a:4]:[c:5]:[c:6]:[c:7](-[O;H0;D2;+0:8]-[CH2;D2;+0:1]-[C:2]-[C:3]):[c:9]
35.8
[{"value": 35.0, "product": "CC=1NC2=CC=C(C=C2C1)OC1=NC=NC2=CC(=CC=C12)OCCCN1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 35.8, "product": "CC=1NC2=CC=C(C=C2C1)OC1=NC=NC2=CC(=CC=C12)OCCCN1CCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
Diisopropyl azodicarboxylate (146 mg, 0.72 mmol) was added to a solution of 7-hydroxy-4-(2-methylindol-5-yloxy)quinazoline (100 mg, 0.34 mmol), triphenyl phosphine (189 mg, 0.72 mol), and 3-pyrrolidinopropan-1-ol (89 mg, 0.686 mmol), (J. Org. Chem. 1988, 53, 3164), in methylene chloride (2.5 ml). After stirring overnig...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]C1
HO-
C(Cl)Cl
null
8
Cc1cc2cc(Oc3ncnc4cc(O)ccc34)ccc2[nH]1.OCCCN1CCCC1>C(Cl)Cl>Cc1cc2cc(Oc3ncnc4cc(OCCCN5CCCC5)ccc34)ccc2[nH]1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-2d8b67f1a8a545bd9972d1da6ea7114f
O=c1[nH]cnc2cc(F)ccc12.OCc1ccccc1>>O=c1[nH]cnc2cc(OCc3ccccc3)ccc12
Cl.[Na].C(C1=CC=CC=C1)O.FC1=CC=C2C(NC=NC2=C1)=O>>C(C1=CC=CC=C1)OC1=CC=C2C(NC=NC2=C1)=O
F[c:8]1[cH:7][c:6]2[n:5][cH:4][nH:3][c:2](=[O:1])[c:19]2[cH:18][cH:17]1.[OH:9][CH2:10][c:11]1[cH:12][cH:13][cH:14][cH:15][cH:16]1>>[O:1]=[c:2]1[nH:3][cH:4][n:5][c:6]2[cH:7][c:8]([O:9][CH2:10][c:11]3[cH:12][cH:13][cH:14][cH:15][cH:16]3)[cH:17][cH:18][c:19]12
O=c1[nH]cnc2cc(F)ccc12.OCc1ccccc1
O=c1[nH]cnc2cc(OCc3ccccc3)ccc12
null
null
O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
ac75d0316beb5e727636a794e424e80db78112f51f640e69f9b28b1404a2e776
a4cafa7bcd156e21cca6eaac1b32e28ec8540642a31181122e6957f3d7559631
O=c1[nH]cnc2cc(OCc3ccccc3)ccc12
F-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[c:4]2:[c:5]:[#7;a:6]:[c:7]:[#7;a:8]:[c:9]:2:[c:10]:1.[OH;D1;+0:11]-[C:12]-[c:13]>>[c:13]-[C:12]-[O;H0;D2;+0:11]-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[c:4]2:[c:5]:[#7;a:6]:[c:7]:[#7;a:8]:[c:9]:2:[c:10]:1
89
[{"value": 89.0, "product": "C(C1=CC=CC=C1)OC1=CC=C2C(NC=NC2=C1)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 88.2, "product": "C(C1=CC=CC=C1)OC1=CC=C2C(NC=NC2=C1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
148
CELSIUS
null
null
Sodium (368 mg, 16 mmol) was added to benzyl alcohol (10 ml, 96 mmol) and the mixture was heated at 148° C. for 30 minutes. 7-Fluoro-3,4-dihydroquinazolin-4-one (656 mg, 4 mmol), (J. Chem. Soc. section B 1967, 449), was added and the mixture maintained at 148° C. for 24 hours. The reaction mixture was allowed to cool, ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary alcohol
Ether
c1ccc2cncnc2c1
c1ccc2cncnc2c1
c1ccc2cncnc2c1.c1ccccc1
HF
O
148
null
O=c1[nH]cnc2cc(F)ccc12.OCc1ccccc1>O>O=c1[nH]cnc2cc(OCc3ccccc3)ccc12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-386c15b33e43484abe8d4c9e2dced546
O=S(Cl)Cl.O=c1[nH]cnc2cc(OCc3ccccc3)ccc12>>Clc1ncnc2cc(OCc3ccccc3)ccc12
C(C1=CC=CC=C1)OC1=CC=C2C(NC=NC2=C1)=O.CN(C)C=O.S(=O)(Cl)Cl>>C(C1=CC=CC=C1)OC1=CC=C2C(=NC=NC2=C1)Cl
O=S(Cl)[Cl:1].O=[c:2]1[nH:3][cH:4][n:5][c:6]2[cH:7][c:8]([O:9][CH2:10][c:11]3[cH:12][cH:13][cH:14][cH:15][cH:16]3)[cH:17][cH:18][c:19]12>>[Cl:1][c:2]1[n:3][cH:4][n:5][c:6]2[cH:7][c:8]([O:9][CH2:10][c:11]3[cH:12][cH:13][cH:14][cH:15][cH:16]3)[cH:17][cH:18][c:19]12
O=S(Cl)Cl.O=c1[nH]cnc2cc(OCc3ccccc3)ccc12
Clc1ncnc2cc(OCc3ccccc3)ccc12
null
null
null
Functional Group Interconversion
OtherReaction
5d38f97f3712b237e9f3fba95a694ccb97b6e400bb6127459a74d91e2bc1ab18
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccc(COc2ccc3cncnc3c2)cc1
Cl-S(=O)-[Cl;H0;D1;+0:1].O=[c;H0;D3;+0:2]1:[nH;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:2]1:[n;H0;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]
89
[{"value": 89.0, "product": "C(C1=CC=CC=C1)OC1=CC=C2C(=NC=NC2=C1)Cl", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
A mixture of 7-benzyloxy-3,4-dihydroquinazolin-4-one (1 g, 43.6 mmol) and DMF (1 ml) in thionyl chloride (100 ml) was heated at reflux for 1.5 hours. Excess thionyl chloride was removed by evaporation and the residue azeotroped with toluene. The residue was partitioned between methylene chloride and water and saturated...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccc2cncnc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.c1ccccc1
HCl
null
null
null
O=S(Cl)Cl.O=c1[nH]cnc2cc(OCc3ccccc3)ccc12>>Clc1ncnc2cc(OCc3ccccc3)ccc12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-08ed20305afe40bbb64522a1ad4d9b3c
Cc1cc2cc(O)ccc2[nH]1.Clc1ncnc2cc(OCc3ccccc3)ccc12>>Cc1cc2cc(Oc3ncnc4cc(OCc5ccccc5)ccc34)ccc2[nH]1
C(C1=CC=CC=C1)OC1=CC=C2C(=NC=NC2=C1)Cl.OC=1C=C2C=C(NC2=CC1)C.C([O-])([O-])=O.[K+].[K+]>>C(C1=CC=CC=C1)OC1=CC=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C
[CH3:1][c:2]1[cH:3][c:4]2[cH:5][c:6]([OH:7])[cH:26][cH:27][c:28]2[nH:29]1.Cl[c:8]1[n:9][cH:10][n:11][c:12]2[cH:13][c:14]([O:15][CH2:16][c:17]3[cH:18][cH:19][cH:20][cH:21][cH:22]3)[cH:23][cH:24][c:25]12>>[CH3:1][c:2]1[cH:3][c:4]2[cH:5][c:6]([O:7][c:8]3[n:9][cH:10][n:11][c:12]4[cH:13][c:14]([O:15][CH2:16][c:17]5[cH:18][c...
Cc1cc2cc(O)ccc2[nH]1.Clc1ncnc2cc(OCc3ccccc3)ccc12
Cc1cc2cc(Oc3ncnc4cc(OCc5ccccc5)ccc34)ccc2[nH]1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1ccc(COc2ccc3c(Oc4ccc5[nH]ccc5c4)ncnc3c2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:6]:[c:5]1:[#7;a:4]:[c:3]:[#7;a:2]:[c;H0;D3;+0:1](-[O;H0;D2;+0:9]-[c:10](:[c:11]):[c:12]):[c:7]:1:[c:8]
81
[{"value": 81.0, "product": "C(C1=CC=CC=C1)OC1=CC=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 80.8, "product": "C(C1=CC=CC=C1)OC1=CC=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
3
HOUR
A solution of 7-benzyloxy-4-chloroquinazoline (2 g, 7.4 mmol), 5-hydroxy-2-methylindole (1.3 g, 8.9 mmol), (prepared as described for the starting material in Example 48), in DMF (20 ml) containing potassium carbonate (1.53 g, 11.1 mmol) was stirred at 80° C. for 3 hours. After cooling, the mixture was poured in portio...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.c1ccccc1
HCl
CN(C)C=O
80
3
Cc1cc2cc(O)ccc2[nH]1.Clc1ncnc2cc(OCc3ccccc3)ccc12>CN(C)C=O>Cc1cc2cc(Oc3ncnc4cc(OCc5ccccc5)ccc34)ccc2[nH]1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-66e62c3f593c499ca4a2ecf6732323a2
Cc1cc2cc(Oc3ncnc4cc(OCc5ccccc5)ccc34)ccc2[nH]1>>Cc1cc2cc(Oc3ncnc4cc(O)ccc34)ccc2[nH]1
C(=O)[O-].[NH4+].C(C1=CC=CC=C1)OC1=CC=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C>>OC1=CC=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C
c1ccc(C[O:15][c:14]2[cH:13][c:12]3[n:11][cH:10][n:9][c:8]([O:7][c:6]4[cH:5][c:4]5[cH:3][c:2]([CH3:1])[nH:22][c:21]5[cH:20][cH:19]4)[c:18]3[cH:17][cH:16]2)cc1>>[CH3:1][c:2]1[cH:3][c:4]2[cH:5][c:6]([O:7][c:8]3[n:9][cH:10][n:11][c:12]4[cH:13][c:14]([OH:15])[cH:16][cH:17][c:18]34)[cH:19][cH:20][c:21]2[nH:22]1
Cc1cc2cc(Oc3ncnc4cc(OCc5ccccc5)ccc34)ccc2[nH]1
Cc1cc2cc(Oc3ncnc4cc(O)ccc34)ccc2[nH]1
null
[Pd]
CN(C)C=O
Deprotection
Hydroxyl benzyl deprotection
36869d1fe85185a14d9eb30bf05178c600a9b6eca277ffaf3803578c30e0bf5d
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
[#7;a:1]:[c:2]:[c:3]:[c:4](-[O;H0;D2;+0:5]-C-c1:c:c:c:c:c:1):[c:6]>>[#7;a:1]:[c:2]:[c:3]:[c:4](-[OH;D1;+0:5]):[c:6]
93
[{"value": 93.0, "product": "OC1=CC=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 92.9, "product": "OC1=CC=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
10% Palladium on charcoal (200 mg) followed by ammonium formate (4.34 g, 69 mmol) were added to a solution of 7-benzyloxy-4-(2-methylindol-5-yloxy)quinazoline (1.75 g, 4.58 mmol) in DMF (60 ml). After stirring for 1 hour at ambient temperature, the mixture was filtered. The filtrate was evaporated. The residue was trit...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
c1ccccc1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
Other
[Pd].CN(C)C=O
null
1
Cc1cc2cc(Oc3ncnc4cc(OCc5ccccc5)ccc34)ccc2[nH]1>[Pd].CN(C)C=O>Cc1cc2cc(Oc3ncnc4cc(O)ccc34)ccc2[nH]1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-842f2abcb05746a680def91007ddf757
CC(C)(C)OC(=O)N1CCC(CO)CC1.Cc1cc2cc(Oc3ncnc4cc(O)ccc34)ccc2[nH]1>>Cc1cc2cc(Oc3ncnc4cc(OCC5CCN(C(=O)OC(C)(C)C)CC5)ccc34)ccc2[nH]1
N(=NC(=O)OC(C)C)C(=O)OC(C)C.OC1=CC=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.OCC1CCN(CC1)C(=O)OC(C)(C)C>>C(C)(C)(C)OC(=O)N1CCC(CC1)COC1=CC=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C
O[CH2:16][CH:17]1[CH2:18][CH2:19][N:20]([C:21](=[O:22])[O:23][C:24]([CH3:25])([CH3:26])[CH3:27])[CH2:28][CH2:29]1.[CH3:1][c:2]1[cH:3][c:4]2[cH:5][c:6]([O:7][c:8]3[n:9][cH:10][n:11][c:12]4[cH:13][c:14]([OH:15])[cH:30][cH:31][c:32]34)[cH:33][cH:34][c:35]2[nH:36]1>>[CH3:1][c:2]1[cH:3][c:4]2[cH:5][c:6]([O:7][c:8]3[n:9][cH:...
CC(C)(C)OC(=O)N1CCC(CO)CC1.Cc1cc2cc(Oc3ncnc4cc(O)ccc34)ccc2[nH]1
Cc1cc2cc(Oc3ncnc4cc(OCC5CCN(C(=O)OC(C)(C)C)CC5)ccc34)ccc2[nH]1
null
null
C(Cl)Cl
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCC3CCNCC3)cc2n1
O-[CH2;D2;+0:1]-[C:2](-[C:3])-[C:4].[#7;a:5]:[c:6]:[c:7]:[c:8](-[OH;D1;+0:9]):[c:10]>>[#7;a:5]:[c:6]:[c:7]:[c:8](-[O;H0;D2;+0:9]-[CH2;D2;+0:1]-[C:2](-[C:3])-[C:4]):[c:10]
68
[{"value": 68.0, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)COC1=CC=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 67.5, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)COC1=CC=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
A solution of 7-hydroxy-4-(2-methylindol-5-yloxy)quinazoline (423 mg, 1.45 mmol), (prepared as described for the starting material in Example 82), triphenylphosphine (685 mg, 2.61 mmol), 4-hydroxymethyl-1-tert-butoxycarbonylpiperidine (500 mg, 2.32 mmol), (prepared as described for the starting material in Example 10),...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HO-
C(Cl)Cl
null
8
CC(C)(C)OC(=O)N1CCC(CO)CC1.Cc1cc2cc(Oc3ncnc4cc(O)ccc34)ccc2[nH]1>C(Cl)Cl>Cc1cc2cc(Oc3ncnc4cc(OCC5CCN(C(=O)OC(C)(C)C)CC5)ccc34)ccc2[nH]1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-854ddcf2d8f646d4b6085429f2c86e2c
COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1O.OCCN1CCCC1>>COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCCN1CCCC1
N(=NC(=O)OC(C)C)C(=O)OC(C)C.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.OCCN1CCCC1.CC=1NC2=CC=C(C=C2C1C)OC1=NC=NC2=CC(=C(C=C12)OC)O>>CC=1NC2=CC=C(C=C2C1C)OC1=NC=NC2=CC(=C(C=C12)OC)OCCN1CCCC1
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[c:15]([CH3:16])[c:17]4[cH:18]3)[n:19][cH:20][n:21][c:22]2[cH:23][c:24]1[OH:25].O[CH2:26][CH2:27][N:28]1[CH2:29][CH2:30][CH2:31][CH2:32]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[...
COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1O.OCCN1CCCC1
COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCCN1CCCC1
null
null
C(Cl)Cl
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCN3CCCC3)cc2n1
O-[CH2;D2;+0:1]-[C:2]-[#7:3].[#7;a:4]:[c:5]:[c:6]:[c:7](-[OH;D1;+0:8]):[c:9]>>[#7:3]-[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:8]-[c:7](:[c:9]):[c:6]:[c:5]:[#7;a:4]
37
[{"value": 37.0, "product": "CC=1NC2=CC=C(C=C2C1C)OC1=NC=NC2=CC(=C(C=C12)OC)OCCN1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 36.8, "product": "CC=1NC2=CC=C(C=C2C1C)OC1=NC=NC2=CC(=C(C=C12)OC)OCCN1CCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
To a suspension of 4-(2,3-dimethylindol-5-yloxy)-7-hydroxy-6-methoxyquinazoline (124 mg, 0.32 mmol) in methylene chloride (2.5 ml) was added triphenylphosphine (179 mg, 0.628 mmol), 1-(2-hydroxyethyl)pyrrolidine (75 mg, 0.65 mmol) followed by diisopropyl azodicarboxylate (134 μl, 0.68 mmol) in portions. After stirring ...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]C1
HO-
C(Cl)Cl
null
8
COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1O.OCCN1CCCC1>C(Cl)Cl>COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCCN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-6794c1b8a77945f7839e5559d033a546
COc1ccc2[nH]c(C)c(C)c2c1>>Cc1[nH]c2ccc(O)cc2c1C
CC=1NC2=CC=C(C=C2C1C)OC.B(Br)(Br)Br.[OH-].[Na+]>>CC=1NC2=CC=C(C=C2C1C)O
C[O:8][c:7]1[cH:6][cH:5][c:4]2[nH:3][c:2]([CH3:1])[c:11]([CH3:12])[c:10]2[cH:9]1>>[CH3:1][c:2]1[nH:3][c:4]2[cH:5][cH:6][c:7]([OH:8])[cH:9][c:10]2[c:11]1[CH3:12]
COc1ccc2[nH]c(C)c(C)c2c1
Cc1[nH]c2ccc(O)cc2c1C
null
null
O
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2[nH]ccc2c1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[OH;D1;+0:1]-[c:2](:[c:3]):[c:4]
77
[{"value": 77.0, "product": "CC=1NC2=CC=C(C=C2C1C)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 76.9, "product": "CC=1NC2=CC=C(C=C2C1C)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
To a solution of 2,3-dimethyl-5-methoxyindole (175 mg, 1 mmol), (J. Chem. Soc. 1957, 3175–3180) in methylene (5 ml) cooled at −60° C. was added boron tribromide (210 μl, 2.2 mmol) dropwise. After completion of addition, the mixture was left to warm up to ambient temperature and was stirred for 1 hour. Water was added a...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1ccc2[nH]ccc2c1
Other
O
null
1
COc1ccc2[nH]c(C)c(C)c2c1>O>Cc1[nH]c2ccc(O)cc2c1C
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-42046bf8cb5d4a69a8401106f59e4bd4
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cc1[nH]c2ccc(O)cc2c1C>>COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCc1ccccc1
C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)Cl)OC.CC=1NC2=CC=C(C=C2C1C)O.C([O-])([O-])=O.[K+].[K+]>>C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=C(NC2=CC1)C)C)OC
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:24]([O:25][CH2:26][c:27]3[cH:28][cH:29][cH:30][cH:31][cH:32]3)[cH:23][c:22]2[n:21][cH:20][n:19]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][c:13]([CH3:14])[c:15]([CH3:16])[c:17]2[cH:18]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[c:...
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cc1[nH]c2ccc(O)cc2c1C
COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCc1ccccc1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1ccc(COc2ccc3c(Oc4ccc5[nH]ccc5c4)ncnc3c2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
98.8
[{"value": 95.0, "product": "C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=C(NC2=CC1)C)C)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 98.8, "product": "C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=C(NC2=CC1)C)C)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
15
MINUTE
Under nitrogen, to a solution of 2,3-dimethyl-5-hydroxyindole (643 mg, 4 mmol), in DMF (10 ml) was added potassium carbonate (690 mg, 5 mmol). After stirring for 15 minutes at ambient temperature, 7-benzyloxy-4-chloro-6-methoxyquinazoline (1 g, 3.33 mmol), (prepared as described for the starting material in Example 1),...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.c1ccccc1
HCl
CN(C)C=O
null
0.25
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cc1[nH]c2ccc(O)cc2c1C>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCc1ccccc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3bfd1ba1cd7d48a1aff557104078bbc4
COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCc1ccccc1>>COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1O
C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=C(NC2=CC1)C)C)OC.C(=O)[O-].[NH4+]>>CC=1NC2=CC=C(C=C2C1C)OC1=NC=NC2=CC(=C(C=C12)OC)O
c1ccc(C[O:25][c:24]2[c:3]([O:2][CH3:1])[cH:4][c:5]3[c:6]([O:7][c:8]4[cH:9][cH:10][c:11]5[nH:12][c:13]([CH3:14])[c:15]([CH3:16])[c:17]5[cH:18]4)[n:19][cH:20][n:21][c:22]3[cH:23]2)cc1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[c:15]([CH3:16])[c:17]4[cH:18]3)[n:19][cH:20][n...
COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCc1ccccc1
COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1O
null
[Pd]
CN(C)C=O
Deprotection
Hydroxyl benzyl deprotection
36869d1fe85185a14d9eb30bf05178c600a9b6eca277ffaf3803578c30e0bf5d
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
[#7;a:1]:[c:2]:[c:3]:[c:4](-[O;H0;D2;+0:5]-C-c1:c:c:c:c:c:1):[c:6]>>[#7;a:1]:[c:2]:[c:3]:[c:4](-[OH;D1;+0:5]):[c:6]
69.8
[{"value": 69.0, "product": "CC=1NC2=CC=C(C=C2C1C)OC1=NC=NC2=CC(=C(C=C12)OC)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 69.8, "product": "CC=1NC2=CC=C(C=C2C1C)OC1=NC=NC2=CC(=C(C=C12)OC)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2.5
HOUR
A solution of 7-benzyloxy-4-(2,3-dimethylindol-5-yloxy)-6-methoxyquinazoline (2 g, 4.7 mmol) in DMF (120 ml) containing ammonium formate (11 gr, 174 mmol) and 10% palladium on charcoal (200 mg) was stirred for 2.5 hours at ambient temperature. The mixture was filtered, and the filtrate was evaporated under vacuum. The ...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
c1ccccc1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
Other
[Pd].CN(C)C=O
null
2.5
COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCc1ccccc1>[Pd].CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-7c482d15c6cb4a9c8b8c79fb205a2341
COCCOCCO.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1O>>COCCOCCOc1cc2ncnc(Oc3ccc4[nH]ccc4c3)c2cc1OC
OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC.COCCOCCO>>N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCOCCOC
O[CH2:7][CH2:6][O:5][CH2:4][CH2:3][O:2][CH3:1].[OH:8][c:9]1[cH:10][c:11]2[n:12][cH:13][n:14][c:15]([O:16][c:17]3[cH:18][cH:19][c:20]4[nH:21][cH:22][cH:23][c:24]4[cH:25]3)[c:26]2[cH:27][c:28]1[O:29][CH3:30]>>[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][CH2:7][O:8][c:9]1[cH:10][c:11]2[n:12][cH:13][n:14][c:15]([O:16][c:17]3[cH:...
COCCOCCO.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1O
COCCOCCOc1cc2ncnc(Oc3ccc4[nH]ccc4c3)c2cc1OC
null
null
null
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
O-[CH2;D2;+0:1]-[C:2]-[#8:3].[#7;a:4]:[c:5]:[c:6]:[c:7](-[OH;D1;+0:8]):[c:9]>>[#7;a:4]:[c:5]:[c:6]:[c:7](-[O;H0;D2;+0:8]-[CH2;D2;+0:1]-[C:2]-[#8:3]):[c:9]
42.2
[{"value": 42.0, "product": "N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCOCCOC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 42.2, "product": "N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCOCCOC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 91, 7-hydroxy-4-(indol-5-yloxy)-6-methoxyquinazoline (89 mg) was reacted with 2-(2-methoxyethoxy)ethanol (70 mg) to give 4-(indol-5yloxy)-6-methoxy-7-(2-(2-methoxyethoxy)ethoxy)quinazoline (50 mg, 42%). Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccc2ncncc2c1.c1ccc2[nH]ccc2c1
HO-
null
null
null
COCCOCCO.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1O>>COCCOCCOc1cc2ncnc(Oc3ccc4[nH]ccc4c3)c2cc1OC
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-007193818dbc4013a176624a6a5b1660
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Oc1ccc2[nH]ccc2c1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCc1ccccc1
C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)Cl)OC.OC=1C=C2C=CNC2=CC1.C([O-])([O-])=O.[K+].[K+]>>C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:22]([O:23][CH2:24][c:25]3[cH:26][cH:27][cH:28][cH:29][cH:30]3)[cH:21][c:20]2[n:19][cH:18][n:17]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][cH:13][cH:14][c:15]2[cH:16]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][cH:13][cH:14][c:15]4[cH:16]3)[n:17][...
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Oc1ccc2[nH]ccc2c1
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCc1ccccc1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1ccc(COc2ccc3c(Oc4ccc5[nH]ccc5c4)ncnc3c2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
88.1
[{"value": 88.0, "product": "C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 88.1, "product": "C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
95
CELSIUS
null
null
A mixture of 7-benzyloxy-4-chloro-6-methoxyquinazoline (3 g, 10 mmol), (prepared as described for the starting material in Example 1), 5-hydroxyindole (1.46 g, 11 mmol) in DMF (30 ml) containing potassium carbonate (2.75 g, 20 mmol) was heated at 95° C. for 2 hours. After cooling the mixture was poured onto water (100 ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.c1ccccc1
HCl
CN(C)C=O
95
null
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Oc1ccc2[nH]ccc2c1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCc1ccccc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-7667d085405e46f48417935fc1ca117f
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCc1ccccc1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1O
C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC.[H][H]>>OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC
c1ccc(C[O:23][c:22]2[c:3]([O:2][CH3:1])[cH:4][c:5]3[c:6]([O:7][c:8]4[cH:9][cH:10][c:11]5[nH:12][cH:13][cH:14][c:15]5[cH:16]4)[n:17][cH:18][n:19][c:20]3[cH:21]2)cc1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][cH:13][cH:14][c:15]4[cH:16]3)[n:17][cH:18][n:19][c:20]2[cH:21][c:22]1[OH:23]
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCc1ccccc1
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1O
null
[Pd]
C(Cl)Cl.CN(C)C=O
Deprotection
Hydroxyl benzyl deprotection
36869d1fe85185a14d9eb30bf05178c600a9b6eca277ffaf3803578c30e0bf5d
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
[#7;a:1]:[c:2]:[c:3]:[c:4](-[O;H0;D2;+0:5]-C-c1:c:c:c:c:c:1):[c:6]>>[#7;a:1]:[c:2]:[c:3]:[c:4](-[OH;D1;+0:5]):[c:6]
44
[{"value": 44.0, "product": "OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 43.9, "product": "OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 7-benzyloxy-4-(indol-5-yloxy)-6-methoxyquinazoline (8 g, 20 mmol) in DMF (50 ml) and methylene chloride (100 ml) containing 10% palladium on charcoal (2 g) was hydrogenated at 1.8 atmospheres pressure until uptake of hydrogen had ceased. The solution was filtered, the catalyst was washed with DMF and the ...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
c1ccccc1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
Other
[Pd].C(Cl)Cl.CN(C)C=O
null
null
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCc1ccccc1>[Pd].C(Cl)Cl.CN(C)C=O>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-62cc52a760534c84916822f65748c4c0
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1ccc2cc[nH]c2c1>>COc1cc2c(Oc3ccc4cc[nH]c4c3)ncnc2cc1OCCCN1CCCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1.OC1=CC=C2C=CNC2=C1.C([O-])([O-])=O.[Cs+].[Cs+]>>N1C=CC2=CC=C(C=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:22]([O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]3)[cH:21][c:20]2[n:19][cH:18][n:17]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[cH:12][cH:13][nH:14][c:15]2[cH:16]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[cH:12][cH:13][nH:14][c...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1ccc2cc[nH]c2c1
COc1cc2c(Oc3ccc4cc[nH]c4c3)ncnc2cc1OCCCN1CCCCC1
null
null
O.CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3cc[nH]c3c2)c2ccc(OCCCN3CCCCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#7;a:9]:[c:10]:[c:11]:[c:12](-[OH;D1;+0:13]):[c:14]>>[#7;a:9]:[c:10]:[c:11]:[c:12](-[O;H0;D2;+0:13]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:14]
94
[{"value": 93.0, "product": "N1C=CC2=CC=C(C=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 94.0, "product": "N1C=CC2=CC=C(C=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
90
CELSIUS
null
null
A solution of 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (200 mg, 0.59 mmol), (prepared as described for the starting material in Example 67), 6-hydroxyindole (96 mg, 0.715 mmol) in DMF (3 ml) containing cesium carbonate (291 mg, 0.894 mmol) was heated at 90° C. for 4 hours. After cooling, the mixture was di...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
O.CN(C)C=O
90
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1ccc2cc[nH]c2c1>O.CN(C)C=O>COc1cc2c(Oc3ccc4cc[nH]c4c3)ncnc2cc1OCCCN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-468fcbe5be244819a8c75295abe707e7
COc1cc2c(Cl)ncnc2cc1OCCCS(C)(=O)=O.Oc1ccc2cc[nH]c2c1>>COc1cc2c(Oc3ccc4cc[nH]c4c3)ncnc2cc1OCCCS(C)(=O)=O
O.ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCS(=O)(=O)C.OC1=CC=C2C=CNC2=C1.C([O-])([O-])=O.[K+].[K+]>>N1C=CC2=CC=C(C=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCS(=O)(=O)C
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:22]([O:23][CH2:24][CH2:25][CH2:26][S:27]([CH3:28])(=[O:29])=[O:30])[cH:21][c:20]2[n:19][cH:18][n:17]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[cH:12][cH:13][nH:14][c:15]2[cH:16]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[cH:12][cH:13][nH:14][c:15]4[cH:16]3)[n...
COc1cc2c(Cl)ncnc2cc1OCCCS(C)(=O)=O.Oc1ccc2cc[nH]c2c1
COc1cc2c(Oc3ccc4cc[nH]c4c3)ncnc2cc1OCCCS(C)(=O)=O
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1ccc2c(Oc3ccc4cc[nH]c4c3)ncnc2c1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#7;a:9]:[c:10]:[c:11]:[c:12](-[OH;D1;+0:13]):[c:14]>>[#7;a:9]:[c:10]:[c:11]:[c:12](-[O;H0;D2;+0:13]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:14]
50.7
[{"value": 50.0, "product": "N1C=CC2=CC=C(C=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCS(=O)(=O)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 50.7, "product": "N1C=CC2=CC=C(C=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCS(=O)(=O)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
90
CELSIUS
null
null
A solution of 4-chloro-6-methoxy-7-(3-methylsulphonylpropoxy)quinazoline (200 mg, 0.6 mmol), (prepared as described for the starting material in Example 50), and 6hydroxyindole (97 mg, 0.73 mmol) in DMF (3 ml) containing potassium carbonate (125 mg, 0.91 mmol) was heated at 90° C. for 2.5 hours. After cooling, water wa...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
HCl
CN(C)C=O
90
null
COc1cc2c(Cl)ncnc2cc1OCCCS(C)(=O)=O.Oc1ccc2cc[nH]c2c1>CN(C)C=O>COc1cc2c(Oc3ccc4cc[nH]c4c3)ncnc2cc1OCCCS(C)(=O)=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-f3367ca3df6c40e0a8ab5df5135e4fd7
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Oc1ccc2cc[nH]c2c1>>COc1cc2c(Oc3ccc4cc[nH]c4c3)ncnc2cc1OCCCN1CCOCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1.OC1=CC=C2C=CNC2=C1>>N1C=CC2=CC=C(C=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:22]([O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][O:30][CH2:31][CH2:32]3)[cH:21][c:20]2[n:19][cH:18][n:17]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[cH:12][cH:13][nH:14][c:15]2[cH:16]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[cH:12][cH:13][nH:14][c:1...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Oc1ccc2cc[nH]c2c1
COc1cc2c(Oc3ccc4cc[nH]c4c3)ncnc2cc1OCCCN1CCOCC1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3cc[nH]c3c2)c2ccc(OCCCN3CCOCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#7;a:9]:[c:10]:[c:11]:[c:12](-[OH;D1;+0:13]):[c:14]>>[#7;a:9]:[c:10]:[c:11]:[c:12](-[O;H0;D2;+0:13]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:14]
60.5
[{"value": 60.0, "product": "N1C=CC2=CC=C(C=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 60.5, "product": "N1C=CC2=CC=C(C=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described for Example 120, 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (200 mg, 0.59 mmol), (prepared as described for the starting material in Example 1), was reacted with 6-hydroxyindole (95 mg, 0.71 mmol) to give 4-(indol-6-yloxy)-6-methoxy-7-(3-morpholinopropoxy)quinaz...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1COCC[NH]1
HCl
null
null
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Oc1ccc2cc[nH]c2c1>>COc1cc2c(Oc3ccc4cc[nH]c4c3)ncnc2cc1OCCCN1CCOCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-616c674376af4e3b9af8c59478602e58
Cc1cc2cc(Oc3ncnc4cc(OCC5CCN(C(=O)OC(C)(C)C)CC5)ccc34)ccc2[nH]1>>Cc1cc2cc(Oc3ncnc4cc(OCC5CCNCC5)ccc34)ccc2[nH]1
C(C)(C)(C)OC(=O)N1CCC(CC1)COC1=CC=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C>>CC=1NC2=CC=C(C=C2C1)OC1=NC=NC2=CC(=CC=C12)OCC1CCNCC1
CC(C)(C)OC(=O)[N:20]1[CH2:19][CH2:18][CH:17]([CH2:16][O:15][c:14]2[cH:13][c:12]3[n:11][cH:10][n:9][c:8]([O:7][c:6]4[cH:5][c:4]5[cH:3][c:2]([CH3:1])[nH:29][c:28]5[cH:27][cH:26]4)[c:25]3[cH:24][cH:23]2)[CH2:22][CH2:21]1>>[CH3:1][c:2]1[cH:3][c:4]2[cH:5][c:6]([O:7][c:8]3[n:9][cH:10][n:11][c:12]4[cH:13][c:14]([O:15][CH2:16]...
Cc1cc2cc(Oc3ncnc4cc(OCC5CCN(C(=O)OC(C)(C)C)CC5)ccc34)ccc2[nH]1
Cc1cc2cc(Oc3ncnc4cc(OCC5CCNCC5)ccc34)ccc2[nH]1
null
null
C(Cl)Cl.C(=O)(C(F)(F)F)O
Reduction
Boc amine deprotection
bf3cd5dc3e17e694d8665c89f5d7e08e8763b18436a633eb66e9bf530b8b0316
a94b29c7264c852156fc1cdd4a0951a4fc26c06d0edc9e50c743825dbf79e3fd
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCC3CCNCC3)cc2n1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1](-[C:2]-[C:3])-[C:4]-[C:5]>>[C:3]-[C:2]-[NH;D2;+0:1]-[C:4]-[C:5]
67
[{"value": 67.0, "product": "CC=1NC2=CC=C(C=C2C1)OC1=NC=NC2=CC(=CC=C12)OCC1CCNCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 66.4, "product": "CC=1NC2=CC=C(C=C2C1)OC1=NC=NC2=CC(=CC=C12)OCC1CCNCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
A suspension of 7-(1-tert-butoxycarbonylpiperidin-4-ylmethoxy)-4-(2-methylindol-5-yloxy)quinazoline (150 mg, 0.31 mmol), (prepared as described in Example 90), in methylene chloride (2 ml) and TFA (1.5 ml) was stirred for 1 hour at ambient temperature. After removal of the volatiles under vacuum the residue was azeotro...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
C1CC[NH]CC1
C1CCNCC1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CCNCC1
HO-
C(Cl)Cl.C(=O)(C(F)(F)F)O
null
1
Cc1cc2cc(Oc3ncnc4cc(OCC5CCN(C(=O)OC(C)(C)C)CC5)ccc34)ccc2[nH]1>C(Cl)Cl.C(=O)(C(F)(F)F)O>Cc1cc2cc(Oc3ncnc4cc(OCC5CCNCC5)ccc34)ccc2[nH]1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-950ddb65fb7545d7ae9e374e2c9a5445
COCC=O.Cc1cc2cc(Oc3ncnc4cc(OCC5CCNCC5)ccc34)ccc2[nH]1>>COCCN1CCC(COc2ccc3c(Oc4ccc5[nH]c(C)cc5c4)ncnc3c2)CC1
CC=1NC2=CC=C(C=C2C1)OC1=NC=NC2=CC(=CC=C12)OCC1CCNCC1.COCC=O>>COCCN1CCC(CC1)COC1=CC=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C
O=[CH:4][CH2:3][O:2][CH3:1].[NH:5]1[CH2:6][CH2:7][CH:8]([CH2:9][O:10][c:11]2[cH:12][cH:13][c:14]3[c:15]([O:16][c:17]4[cH:18][cH:19][c:20]5[nH:21][c:22]([CH3:23])[cH:24][c:25]5[cH:26]4)[n:27][cH:28][n:29][c:30]3[cH:31]2)[CH2:32][CH2:33]1>>[CH3:1][O:2][CH2:3][CH2:4][N:5]1[CH2:6][CH2:7][CH:8]([CH2:9][O:10][c:11]2[cH:12][c...
COCC=O.Cc1cc2cc(Oc3ncnc4cc(OCC5CCNCC5)ccc34)ccc2[nH]1
COCCN1CCC(COc2ccc3c(Oc4ccc5[nH]c(C)cc5c4)ncnc3c2)CC1
null
null
null
Heteroatom Alkylation and Arylation
reductive amination
d0e659bc8d1e29e09a61320b4c537e66ad57335a51368c8bd48de9bdffa59372
2d03f38884b1fbb0c0d6e6f2de31afb25102fec87f347c3a123e064c1bfef0ad
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCC3CCNCC3)cc2n1
O=[CH;D2;+0:1]-[C:2]-[#8:3].[C:4]-[C:5]-[NH;D2;+0:6]-[C:7]-[C:8]>>[#8:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:6](-[C:5]-[C:4])-[C:7]-[C:8]
46.4
[{"value": 46.0, "product": "COCCN1CCC(CC1)COC1=CC=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 46.4, "product": "COCCN1CCC(CC1)COC1=CC=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described for Example 71, 4-(2-methylindol-5-yloxy)-7-(piperidin-4-ylmethoxy)quinazoline (150 mg, 0.386 mmol), (prepared as described in Example 122), was reacted with methoxyacetaldehyde (83 mg, 0.772 mmol), (prepared as described for the starting material in Example 71), to give 7...
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Secondary amine
Tertiary amine
C1CCNCC1
C1CC[NH]CC1
C1CC[NH]CC1.c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
Other
null
null
null
COCC=O.Cc1cc2cc(Oc3ncnc4cc(OCC5CCNCC5)ccc34)ccc2[nH]1>>COCCN1CCC(COc2ccc3c(Oc4ccc5[nH]c(C)cc5c4)ncnc3c2)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-c3980b4011204cfe93b1fe678c2f67c0
CCS(=O)(=O)CCCO.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O>>CCS(=O)(=O)CCCOc1cc2ncnc(Oc3ccc4[nH]c(C)cc4c3)c2cc1OC
N(=NC(=O)OCC)C(=O)OCC.OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC.C(C)S(=O)(=O)CCCO.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1>>C(C)S(=O)(=O)CCCOC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC
O[CH2:8][CH2:7][CH2:6][S:3]([CH2:2][CH3:1])(=[O:4])=[O:5].[OH:9][c:10]1[cH:11][c:12]2[n:13][cH:14][n:15][c:16]([O:17][c:18]3[cH:19][cH:20][c:21]4[nH:22][c:23]([CH3:24])[cH:25][c:26]4[cH:27]3)[c:28]2[cH:29][c:30]1[O:31][CH3:32]>>[CH3:1][CH2:2][S:3](=[O:4])(=[O:5])[CH2:6][CH2:7][CH2:8][O:9][c:10]1[cH:11][c:12]2[n:13][cH:...
CCS(=O)(=O)CCCO.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O
CCS(=O)(=O)CCCOc1cc2ncnc(Oc3ccc4[nH]c(C)cc4c3)c2cc1OC
null
null
C(Cl)Cl
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
O-[CH2;D2;+0:1]-[C:2]-[C:3].[#7;a:4]:[c:5]:[c:6]:[c:7](-[OH;D1;+0:8]):[c:9]>>[#7;a:4]:[c:5]:[c:6]:[c:7](-[O;H0;D2;+0:8]-[CH2;D2;+0:1]-[C:2]-[C:3]):[c:9]
55.2
[{"value": 55.0, "product": "C(C)S(=O)(=O)CCCOC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 55.2, "product": "C(C)S(=O)(=O)CCCOC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
Diethyl azodicarboxylate (117 mg, 0.67 mmol) was added in portions to a solution of 7-hydroxy-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (120 mg, 0.37 mmol), (prepared as described in Example 49), and 3-(ethylsulphonyl)-1-propanol (74 mg, 0.48 mmol) in methylene chloride (3.5 ml) and triphenylphosphine (176 mg, 0.6...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccc2ncncc2c1.c1ccc2[nH]ccc2c1
HO-
C(Cl)Cl
null
2
CCS(=O)(=O)CCCO.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O>C(Cl)Cl>CCS(=O)(=O)CCCOc1cc2ncnc(Oc3ccc4[nH]c(C)cc4c3)c2cc1OC
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-5c132ae4580f451eaf6a3733dd9284dd
CCS(=O)(=O)CCCO.COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1O>>CCS(=O)(=O)CCCOc1cc2ncnc(Oc3ccc4[nH]c(C)c(C)c4c3)c2cc1OC
CC=1NC2=CC=C(C=C2C1C)OC1=NC=NC2=CC(=C(C=C12)OC)O.C(C)S(=O)(=O)CCCO>>CC=1NC2=CC=C(C=C2C1C)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCS(=O)(=O)CC
O[CH2:8][CH2:7][CH2:6][S:3]([CH2:2][CH3:1])(=[O:4])=[O:5].[OH:9][c:10]1[cH:11][c:12]2[n:13][cH:14][n:15][c:16]([O:17][c:18]3[cH:19][cH:20][c:21]4[nH:22][c:23]([CH3:24])[c:25]([CH3:26])[c:27]4[cH:28]3)[c:29]2[cH:30][c:31]1[O:32][CH3:33]>>[CH3:1][CH2:2][S:3](=[O:4])(=[O:5])[CH2:6][CH2:7][CH2:8][O:9][c:10]1[cH:11][c:12]2[...
CCS(=O)(=O)CCCO.COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1O
CCS(=O)(=O)CCCOc1cc2ncnc(Oc3ccc4[nH]c(C)c(C)c4c3)c2cc1OC
null
null
null
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
O-[CH2;D2;+0:1]-[C:2]-[C:3].[#7;a:4]:[c:5]:[c:6]:[c:7](-[OH;D1;+0:8]):[c:9]>>[#7;a:4]:[c:5]:[c:6]:[c:7](-[O;H0;D2;+0:8]-[CH2;D2;+0:1]-[C:2]-[C:3]):[c:9]
57
[{"value": 57.0, "product": "CC=1NC2=CC=C(C=C2C1C)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCS(=O)(=O)CC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 0.1, "product": "CC=1NC2=CC=C(C=C2C1C)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCS(=O)(=O)CC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described for Example 124, 4-(2,3-dimethylindol-5-yloxy)-7-hydroxy-6-methoxyquinazoline (120 mg, 0.36 mol), (prepared as described for the starting material in Example 91), was reacted with 3-(ethylsulphonyl)-1-propanol (71 mg, 0.46 mol), (prepared as described for the starting mate...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccc2ncncc2c1.c1ccc2[nH]ccc2c1
HO-
null
null
null
CCS(=O)(=O)CCCO.COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1O>>CCS(=O)(=O)CCCOc1cc2ncnc(Oc3ccc4[nH]c(C)c(C)c4c3)c2cc1OC
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-96881d55c9224543ab8da979c8651f3b
OCCc1ccncc1>>OCCC1CCNCC1
OCCC1=CC=NC=C1>>N1CCC(CC1)CCO
[OH:1][CH2:2][CH2:3][c:4]1[cH:5][cH:6][n:7][cH:8][cH:9]1>>[OH:1][CH2:2][CH2:3][CH:4]1[CH2:5][CH2:6][NH:7][CH2:8][CH2:9]1
OCCc1ccncc1
OCCC1CCNCC1
null
[Pt]=O
C(C)(=O)O
Reduction
OtherReaction
8a6c78a63989dd47e282eb33ae5ce6bfcead5defaa210963e9125c31297ee886
2b7f370a519e29b4dede190aa36b37f30822496e32f2c8bfa9736e631bde52e2
C1CCNCC1
[C:1]-[C:2]-[c;H0;D3;+0:3]1:[cH;D2;+0:4]:[cH;D2;+0:5]:[n;H0;D2;+0:6]:[cH;D2;+0:7]:[cH;D2;+0:8]:1>>[C:1]-[C:2]-[CH;D3;+0:3]1-[CH2;D2;+0:4]-[CH2;D2;+0:5]-[NH;D2;+0:6]-[CH2;D2;+0:7]-[CH2;D2;+0:8]-1
46
[{"value": 46.0, "product": "N1CCC(CC1)CCO", "details": "PERCENTYIELD", "is_desired": false}, {"value": 0.0, "product": "N1CCC(CC1)CCO", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
20
HOUR
A solution of 4-(2-hydroxyethyl)pyridine (1.8 g, 14.6 mol) in acetic acid (15 ml) containing platinum oxide (200 mg) was hydrogenated for 20 hours at 3.3–4 atmospheres pressure. After filtration, the filtrate was evaporated and azeotroped twice with toluene. The residue was triturated with 2N sodium hydroxide and solid...
10.6084/m9.figshare.5104873.v1
null
null
Secondary amine
c1ccncc1
C1CCNCC1
C1CCNCC1
null
[Pt]=O.C(C)(=O)O
null
20
OCCc1ccncc1>[Pt]=O.C(C)(=O)O>OCCC1CCNCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a076f878d6d84a3b975a5319280693d3
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Cc1cc2ccc(O)cc2[nH]1>>COc1cc2c(Oc3ccc4cc(C)[nH]c4c3)ncnc2cc1OCCCN1CCOCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1.OC1=CC=C2C=C(NC2=C1)C>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)OC1=CC=C2C=C(NC2=C1)C
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:23]([O:24][CH2:25][CH2:26][CH2:27][N:28]3[CH2:29][CH2:30][O:31][CH2:32][CH2:33]3)[cH:22][c:21]2[n:20][cH:19][n:18]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[cH:12][c:13]([CH3:14])[nH:15][c:16]2[cH:17]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[cH:12][c:13]([C...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Cc1cc2ccc(O)cc2[nH]1
COc1cc2c(Oc3ccc4cc(C)[nH]c4c3)ncnc2cc1OCCCN1CCOCC1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3cc[nH]c3c2)c2ccc(OCCCN3CCOCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#7;a:9]:[c:10]:[c:11]:[c:12](-[OH;D1;+0:13]):[c:14]>>[#7;a:9]:[c:10]:[c:11]:[c:12](-[O;H0;D2;+0:13]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:14]
73
[{"value": 73.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)OC1=CC=C2C=C(NC2=C1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 0.1, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)OC1=CC=C2C=C(NC2=C1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described for Example 121, 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (160 mg, 0.47 mol), (prepared as described for the starting material in Example 1), was reacted with 6-hydroxy-2-methylindole (84 mg, 0.57 mol), (Eur. J. Med. Chem. 1975, 10, 187), to give 6-methoxy-4-(...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1COCC[NH]1
HCl
null
null
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Cc1cc2ccc(O)cc2[nH]1>>COc1cc2c(Oc3ccc4cc(C)[nH]c4c3)ncnc2cc1OCCCN1CCOCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-6921e7f806d94a5999c24a7292ff9bf9
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCC1CCN(C(=O)OC(C)(C)C)CC1.Cc1cc2cc(Oc3ncnc4cc(OCC5CCNCC5)ccc34)ccc2[nH]1>>COc1cc2cnc(Oc3ccc4[nH]c(C)cc4c3)nc2cc1OCCC1CCNCC1
CC=1NC2=CC=C(C=C2C1)OC1=NC=NC2=CC(=CC=C12)OCC1CCNCC1.C(C)(C)(C)OC(=O)N1CCC(CC1)CCOC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC>>COC=1C=C2C=NC(=NC2=CC1OCCC1CCNCC1)OC=1C=C2C=C(NC2=CC1)C
Cc1cc2cc(O[c:6]3[c:5]4[cH:4][c:3]([O:2][CH3:1])[c:23]([O:24][CH2:25][CH2:26][CH:27]5[CH2:28][CH2:29][N:30](C(=O)OC(C)(C)C)[CH2:31][CH2:32]5)[cH:22][c:21]4[n:20][cH:8][n:7]3)ccc2[nH]1.c1nc([O:9][c:10]2[cH:11][cH:12][c:13]3[nH:14][c:15]([CH3:16])[cH:17][c:18]3[cH:19]2)c2ccc(OCC3CCNCC3)cc2n1>>[CH3:1][O:2][c:3]1[cH:4][c:5]...
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCC1CCN(C(=O)OC(C)(C)C)CC1.Cc1cc2cc(Oc3ncnc4cc(OCC5CCNCC5)ccc34)ccc2[nH]1
COc1cc2cnc(Oc3ccc4[nH]c(C)cc4c3)nc2cc1OCCC1CCNCC1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
0d140802bf1a07c94371db54b4dff07acf8ee243d07b0abe7af3b6d3e1c97e21
c689fc1bd5bc1d24ed683f9083af69e41a219bca148131b30f50ea01e2336bac
c1cc2cc(Oc3ncc4ccc(OCCC5CCNCC5)cc4n3)ccc2[nH]1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1](-[C:2]-[C:3])-[C:4]-[C:5].C-c1:[nH]:c2:c:c:c(-O-[c;H0;D3;+0:6]3:[#7;a:7]:[cH;D2;+0:8]:[#7;a:9]:[c:10](:[c:11]):[c:12]:3:[c:13]):c:c:2:c:1.[c:14]:[c:15](-[O;H0;D2;+0:16]-c1:n:c:n:c2:c:c(-O-C-C3-C-C-N-C-C-3):c:c:c:1:2):[c:17]>>[C:3]-[C:2]-[NH;D2;+0:1]-[C:4]-[C:5].[c:14]:[c:15](-[O;H0;D2...
87
[{"value": 87.0, "product": "COC=1C=C2C=NC(=NC2=CC1OCCC1CCNCC1)OC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described for the synthesis of 4-(2-methylindol-5-yloxy)-7-(piperidin-4-ylmethoxy)quinazoline, (prepared as described in Example 122), 7-(2-(1-tert-butoxycarbonylpiperidin-4-yl)ethoxy)-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (400 mg, 0.75 mmol), (prepared as described in Exam...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Ether.Ether.Ether.Secondary amine.Boc
Ether.Secondary amine
c1ccc2[nH]ccc2c1.C1CC[NH]CC1.c1ccc2ncncc2c1.c1ccc2ncncc2c1.C1CCNCC1
c1ccc2ncncc2c1.C1CCNCC1
c1ccc2ncncc2c1.c1ccc2[nH]ccc2c1.C1CCNCC1
HO-
null
null
null
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCC1CCN(C(=O)OC(C)(C)C)CC1.Cc1cc2cc(Oc3ncnc4cc(OCC5CCNCC5)ccc34)ccc2[nH]1>>COc1cc2cnc(Oc3ccc4[nH]c(C)cc4c3)nc2cc1OCCC1CCNCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-2003344db462457e85182b1317dcee08
COc1cc2c(Nc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1O.OC/C=C/CN1CCCC1>>COc1cc2c(Nc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OC/C=C/CN1CCCC1
N(=NC(=O)OCC)C(=O)OCC.CC=1NC2=CC=C(C=C2C1C)NC1=NC=NC2=CC(=C(C=C12)OC)O.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.N1(CCCC1)C/C=C/CO>>CC=1NC2=CC=C(C=C2C1C)NC1=NC=NC2=CC(=C(C=C12)OC)OC\C=C\CN1CCCC1
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[c:15]([CH3:16])[c:17]4[cH:18]3)[n:19][cH:20][n:21][c:22]2[cH:23][c:24]1[OH:25].O[CH2:26]/[CH:27]=[CH:28]/[CH2:29][N:30]1[CH2:31][CH2:32][CH2:33][CH2:34]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]3[cH:9][cH:10][c:11]4[nH:1...
COc1cc2c(Nc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1O.OC/C=C/CN1CCCC1
COc1cc2c(Nc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OC/C=C/CN1CCCC1
null
null
ClCCl.CN(C)C=O
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
C(=C/CN1CCCC1)\COc1ccc2c(Nc3ccc4[nH]ccc4c3)ncnc2c1
O-[CH2;D2;+0:1]/[C:2]=[C:3]/[C:4]-[#7:5].[#7;a:6]:[c:7]:[c:8]:[c:9](-[OH;D1;+0:10]):[c:11]>>[#7:5]-[C:4]/[C:3]=[C:2]/[CH2;D2;+0:1]-[O;H0;D2;+0:10]-[c:9](:[c:11]):[c:8]:[c:7]:[#7;a:6]
55.7
[{"value": 55.0, "product": "CC=1NC2=CC=C(C=C2C1C)NC1=NC=NC2=CC(=C(C=C12)OC)OC\\C=C\\CN1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 55.7, "product": "CC=1NC2=CC=C(C=C2C1C)NC1=NC=NC2=CC(=C(C=C12)OC)OC\\C=C\\CN1CCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
8
HOUR
Diethyl azodicarboxylate (65 μl, 0.4 mmol) was added in portions to a suspension of 4-(2,3-dimethylindol-5-ylamino)-7-hydroxy-6-methoxyquinazoline (68 mg, 0.2 mmol), triphenylphosphine (107 mg, 0.4 mmol), (E)-4-(pyrrolidin-1-yl)but-2-en-1-ol (40 mg, 0.28 mmol) in DMF (0.4 ml) and dichloromethane (1.5 ml) cooled at 0° C...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]C1
HO-
ClCCl.CN(C)C=O
0
8
COc1cc2c(Nc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1O.OC/C=C/CN1CCCC1>ClCCl.CN(C)C=O>COc1cc2c(Nc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OC/C=C/CN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-92d2445662e34e878073936ee3d26753
C1CCNC1.OCC#CCCl>>OCC#CCN1CCCC1
N1CCCC1.ClCC#CCO>>N1(CCCC1)CC#CCO
[NH:6]1[CH2:7][CH2:8][CH2:9][CH2:10]1.Cl[CH2:5][C:4]#[C:3][CH2:2][OH:1]>>[OH:1][CH2:2][C:3]#[C:4][CH2:5][N:6]1[CH2:7][CH2:8][CH2:9][CH2:10]1
C1CCNC1.OCC#CCCl
OCC#CCN1CCCC1
null
null
C1(=CC=CC=C1)C
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
19b442dc26882f89f7423416f5e0a16bdb8e48776df57991434a0634e21f0505
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
C1CCNC1
Cl-[CH2;D2;+0:1]-[C:2]#[C:3]-[C:4].[C:5]1-[C:6]-[C:7]-[C:8]-[NH;D2;+0:9]-1>>[C:4]-[C:3]#[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:9]1-[C:5]-[C:6]-[C:7]-[C:8]-1
69
[{"value": 69.0, "product": "N1(CCCC1)CC#CCO", "details": "PERCENTYIELD", "is_desired": false}, {"value": 68.6, "product": "N1(CCCC1)CC#CCO", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
null
null
Pyrrolidine (7.8 ml, 94 mmol) was added dropwise to a solution of 4-chlorobut-2-yn-1-ol (4.74 g, 45 mmol) in toluene (40 ml) and the mixture stirred and heated at 60° C. for 1 hour. The volatiles were removed by evaporation and the residue was purified by chromatography eluting with methylene chloride/methanol (96/4) t...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1CCNC1
C1CC[NH]C1
C1CC[NH]C1
HCl
C1(=CC=CC=C1)C
60
null
C1CCNC1.OCC#CCCl>C1(=CC=CC=C1)C>OCC#CCN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-7278cd0e3a4a44c2af3637ec94e801d7
OCC#CCN1CCCC1>>OC/C=C/CN1CCCC1
N1(CCCC1)CC#CCO.[H-].[Al+3].[Li+].[H-].[H-].[H-].[OH-].[Na+]>>N1(CCCC1)C/C=C/CO
[OH:1][CH2:2][C:3]#[C:4][CH2:5][N:6]1[CH2:7][CH2:8][CH2:9][CH2:10]1>>[OH:1][CH2:2]/[CH:3]=[CH:4]/[CH2:5][N:6]1[CH2:7][CH2:8][CH2:9][CH2:10]1
OCC#CCN1CCCC1
OC/C=C/CN1CCCC1
null
null
C1CCOC1
Reduction
Hydrogenation (triple to double)
2bb8d5b532a2781e0a7c069a5cd3e8a7e8d44660c0ec1d9e17c04d8ba2cb383b
1990560e9c55934bde8ca0feaed9c61d80f37f94f0cf240a9929dc374d0a33aa
C1CCNC1
[#7:1]-[C:2]-[C;H0;D2;+0:3]#[C;H0;D2;+0:4]-[C:5]-[O;D1;H1:6]>>[#7:1]-[C:2]/[CH;D2;+0:3]=[CH;D2;+0:4]/[C:5]-[O;D1;H1:6]
70.6
[{"value": 70.0, "product": "N1(CCCC1)C/C=C/CO", "details": "PERCENTYIELD", "is_desired": false}, {"value": 70.6, "product": "N1(CCCC1)C/C=C/CO", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
null
null
A solution of 4-(pyrrolidin-1-yl)but-2-yn-1-ol (4.3 g, 31 mmol) in THF (20 ml) was added dropwise to a suspension of lithium aluminium hydride (2.35 g, 62 mmol) in anhydrous THF (8 ml) and the mixture stirred and heated at 60° C. for 2 hours. The mixture was cooled to 5° C. and 2M aqueous sodium hydroxide solution (28 ...
10.6084/m9.figshare.5104873.v1
null
Alkyne
null
null
null
C1CC[NH]C1
null
C1CCOC1
60
null
OCC#CCN1CCCC1>C1CCOC1>OC/C=C/CN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-035104362d2841e8bfe1b89af72f538b
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cc1[nH]c2ccc(N)cc2c1C>>COc1cc2c(Nc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCc1ccccc1
Cl.ClC1=NC=NC2=CC(=C(C=C12)OC)OCC1=CC=CC=C1.NC=1C=C2C(=C(NC2=CC1)C)C>>C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)NC=1C=C2C(=C(NC2=CC1)C)C)OC
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:24]([O:25][CH2:26][c:27]3[cH:28][cH:29][cH:30][cH:31][cH:32]3)[cH:23][c:22]2[n:21][cH:20][n:19]1.[NH2:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][c:13]([CH3:14])[c:15]([CH3:16])[c:17]2[cH:18]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[...
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cc1[nH]c2ccc(N)cc2c1C
COc1cc2c(Nc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCc1ccccc1
null
null
C(C)(C)O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(COc2ccc3c(Nc4ccc5[nH]ccc5c4)ncnc3c2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[NH2;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[NH;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
107.5
[{"value": 107.5, "product": "C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)NC=1C=C2C(=C(NC2=CC1)C)C)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
A solution of 4-chloro-6-methoxy-7-benzyloxyquinazoline (7 g, 23 mmol), (prepared as described for the starting material in Example 1), and 5-amino-2,3-dimethylindole (4.5 g, 28 mmol) in isopropanol (90 ml) containing 6.2 N hydrogen chloride in isopropanol (380 μl) was heated at relux for 3 hours and stirred overnight ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.c1ccccc1
HCl
C(C)(C)O
null
8
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cc1[nH]c2ccc(N)cc2c1C>C(C)(C)O>COc1cc2c(Nc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCc1ccccc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-0e3fbd87ffc2460d8f1d0cd56bee119e
COc1cc2c(Nc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCc1ccccc1>>COc1cc2c(Nc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1O
C(=O)[O-].[NH4+].C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)NC=1C=C2C(=C(NC2=CC1)C)C)OC.N>>CC=1NC2=CC=C(C=C2C1C)NC1=NC=NC2=CC(=C(C=C12)OC)O
c1ccc(C[O:25][c:24]2[c:3]([O:2][CH3:1])[cH:4][c:5]3[c:6]([NH:7][c:8]4[cH:9][cH:10][c:11]5[nH:12][c:13]([CH3:14])[c:15]([CH3:16])[c:17]5[cH:18]4)[n:19][cH:20][n:21][c:22]3[cH:23]2)cc1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[c:15]([CH3:16])[c:17]4[cH:18]3)[n:19][cH:20]...
COc1cc2c(Nc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCc1ccccc1
COc1cc2c(Nc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1O
null
[Pd]
CO.CN(C)C=O
Deprotection
Hydroxyl benzyl deprotection
36869d1fe85185a14d9eb30bf05178c600a9b6eca277ffaf3803578c30e0bf5d
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2c(Nc3ccc4[nH]ccc4c3)ncnc2c1
[#7;a:1]:[c:2]:[c:3]:[c:4](-[O;H0;D2;+0:5]-C-c1:c:c:c:c:c:1):[c:6]>>[#7;a:1]:[c:2]:[c:3]:[c:4](-[OH;D1;+0:5]):[c:6]
75
[{"value": 75.0, "product": "CC=1NC2=CC=C(C=C2C1C)NC1=NC=NC2=CC(=C(C=C12)OC)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 74.8, "product": "CC=1NC2=CC=C(C=C2C1C)NC1=NC=NC2=CC(=C(C=C12)OC)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
Ammonium formate (20 g, 326 mmol) and 10% palladium on carbon (1 g) were added to a solution of 7-benzyloxy-4-(2,3-dimethylindol-5-ylamino)-6-methoxyquinazoline (10 g, 22 mmol) in DMF (100 ml) and methanol (300 ml). After stirring for 3 hours at ambient temperature, aqueous ammonia (120 ml) was added. The precipitate w...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
c1ccccc1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
Other
[Pd].CO.CN(C)C=O
null
3
COc1cc2c(Nc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCc1ccccc1>[Pd].CO.CN(C)C=O>COc1cc2c(Nc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-eb4511e2bc87448799845d8aeb098c6f
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1cc2ccc(O)cc2[nH]1>>COc1cc2c(Oc3ccc4cc(C)[nH]c4c3)ncnc2cc1OCCCN1CCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1.OC1=CC=C2C=C(NC2=C1)C>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCC1)OC1=CC=C2C=C(NC2=C1)C
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:23]([O:24][CH2:25][CH2:26][CH2:27][N:28]3[CH2:29][CH2:30][CH2:31][CH2:32]3)[cH:22][c:21]2[n:20][cH:19][n:18]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[cH:12][c:13]([CH3:14])[nH:15][c:16]2[cH:17]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[cH:12][c:13]([CH3:14]...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1cc2ccc(O)cc2[nH]1
COc1cc2c(Oc3ccc4cc(C)[nH]c4c3)ncnc2cc1OCCCN1CCCC1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3cc[nH]c3c2)c2ccc(OCCCN3CCCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#7;a:9]:[c:10]:[c:11]:[c:12](-[OH;D1;+0:13]):[c:14]>>[#7;a:9]:[c:10]:[c:11]:[c:12](-[O;H0;D2;+0:13]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:14]
85
[{"value": 85.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCC1)OC1=CC=C2C=C(NC2=C1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 83.6, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCC1)OC1=CC=C2C=C(NC2=C1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described for Example 121, 4-chloro-6-methoxy-7-(3-pyrrolidinopropoxy)quinazoline (150 mg, 0.47 mmol), (prepared as described for the starting material in Example 9), was reacted with 6-hydroxy-2-methylindole (83 mg, 0.56 mol), (Eur. J. Med. Chem. 1975, 10, 187), to give 6-methoxy-4...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]C1
HCl
null
null
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1cc2ccc(O)cc2[nH]1>>COc1cc2c(Oc3ccc4cc(C)[nH]c4c3)ncnc2cc1OCCCN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-8c23736e470648e4ac1d23345969519a
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Cc1cc2cc(O)ccc2n1C>>COc1cc2c(Oc3ccc4c(c3)cc(C)n4C)ncnc2cc1OCCCN1CCOCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1.CN1C(=CC2=CC(=CC=C12)O)C>>CN1C(=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1)C
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:24]([O:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:30][CH2:31][O:32][CH2:33][CH2:34]3)[cH:23][c:22]2[n:21][cH:20][n:19]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[c:12]([cH:13]1)[cH:14][c:15]([CH3:16])[n:17]2[CH3:18]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[c:12](...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Cc1cc2cc(O)ccc2n1C
COc1cc2c(Oc3ccc4c(c3)cc(C)n4C)ncnc2cc1OCCCN1CCOCC1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCOCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
74
[{"value": 74.0, "product": "CN1C(=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 73.4, "product": "CN1C(=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 120 OR 121 PER PP, 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (160 mg, 0.48 mmol), (prepared as described for the starting material in Example 1), was reacted with 1,2-dimethyl-5-hydroxyindole (92 mg, 0.57 mol), (Tetrahedron 1994, 50, 13433), to give ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1COCC[NH]1
HCl
null
null
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Cc1cc2cc(O)ccc2n1C>>COc1cc2c(Oc3ccc4c(c3)cc(C)n4C)ncnc2cc1OCCCN1CCOCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3ebf27f7d3aa4b389ebd546dabb1ff57
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCN(C)C(=O)OC(C)(C)C>>CNCCOc1cc2ncnc(Oc3ccc4[nH]c(C)cc4c3)c2cc1OC
COC=1C=C2C(=NC=NC2=CC1OCCN(C(=O)OC(C)(C)C)C)OC=1C=C2C=C(NC2=CC1)C.C(=O)(C(F)(F)F)O>>COC=1C=C2C(=NC=NC2=CC1OCCNC)OC=1C=C2C=C(NC2=CC1)C
CC(C)(C)OC(=O)[N:2]([CH3:1])[CH2:3][CH2:4][O:5][c:6]1[cH:7][c:8]2[n:9][cH:10][n:11][c:12]([O:13][c:14]3[cH:15][cH:16][c:17]4[nH:18][c:19]([CH3:20])[cH:21][c:22]4[cH:23]3)[c:24]2[cH:25][c:26]1[O:27][CH3:28]>>[CH3:1][NH:2][CH2:3][CH2:4][O:5][c:6]1[cH:7][c:8]2[n:9][cH:10][n:11][c:12]([O:13][c:14]3[cH:15][cH:16][c:17]4[nH:...
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCN(C)C(=O)OC(C)(C)C
CNCCOc1cc2ncnc(Oc3ccc4[nH]c(C)cc4c3)c2cc1OC
null
null
C(Cl)Cl
Reduction
Boc amine deprotection
bbda4640db5f48af4538caded12fdadd56eacd6d4e5f7aefe46282d665df167e
a94b29c7264c852156fc1cdd4a0951a4fc26c06d0edc9e50c743825dbf79e3fd
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1](-[C;D1;H3:2])-[C:3]-[C:4]>>[C:4]-[C:3]-[NH;D2;+0:1]-[C;D1;H3:2]
82
[{"value": 82.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCNC)OC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 81.8, "product": "COC=1C=C2C(=NC=NC2=CC1OCCNC)OC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
A solution of 6-methoxy-4-(2-methylindol-5-yloxy)-7-(2-(N-methyl-N-tert-butoxycarbonylamino)ethoxy)quinazoline (550 mg, 1.15 mmol), (prepared as described in Example 149), in methylene chloride (10 ml) containing TFA (12 ml) was stirred for 3 hours at ambient temperature. After removal of the volatiles under vacuum, th...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
null
null
c1ccc2ncncc2c1.c1ccc2[nH]ccc2c1
HO-
C(Cl)Cl
null
3
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCN(C)C(=O)OC(C)(C)C>C(Cl)Cl>CNCCOc1cc2ncnc(Oc3ccc4[nH]c(C)cc4c3)c2cc1OC
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-5246d30a745044a6a9424dedab8276b3
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCNCC1.N#CCCl>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC(CC#N)C1CCNCC1
COC=1C=C2C(=NC=NC2=CC1OCC1CCNCC1)OC=1C=C2C=C(NC2=CC1)C.ClCC#N.C([O-])([O-])=O.[K+].[K+].[I-].[K+]>>C(#N)CC(OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)C1CCNCC1
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[cH:15][c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[O:24][CH2:25][CH:29]1[CH2:30][CH2:31][NH:32][CH2:33][CH2:34]1.Cl[CH2:26][C:27]#[N:28]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13...
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCNCC1.N#CCCl
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC(CC#N)C1CCNCC1
null
null
O.CN(C)C=O
C-C Coupling
OtherReaction
5e2d5f735161ca1f0f824efe0b27c87d9be398df1c44db4f86736c90dd790b94
2c1c1647472d7e3cff37f0f3aad955b760f0ad2f8b7aa7e7825b1c0344bab3bb
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCC3CCNCC3)cc2n1
Cl-[CH2;D2;+0:1]-[C:2]#[N;D1;H0:3].[C:4]-[C:5](-[CH2;D2;+0:6]-[#8:7]-[c:8])-[C:9]>>[C:4]-[C:5](-[CH;D3;+0:6](-[#8:7]-[c:8])-[CH2;D2;+0:1]-[C:2]#[N;D1;H0:3])-[C:9]
66.4
[{"value": 66.0, "product": "C(#N)CC(OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)C1CCNCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 66.4, "product": "C(#N)CC(OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)C1CCNCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
A mixture of 6-methoxy-4-(2-methylindol-5-yloxy)-7-(piperidin-4-ylmethoxy)quinazoline (419 mg, 1 mmol), (prepared as described in Example 70), in DMF (6 ml) containing chloroacetonitrile (114 mg, 1.5 mmol), potassium carbonate (346 mg, 2.5 mmol) and potassium iodide (50 mg, 0.3 mmol) was stirred at ambient temperature ...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ether
Ether
null
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CCNCC1
HCl
O.CN(C)C=O
null
8
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCNCC1.N#CCCl>O.CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC(CC#N)C1CCNCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-c61c81cc31e44983a487963fd3015893
COc1cc2c(Cl)ncnc2cc1OCCCN(C)S(C)(=O)=O.Oc1ccc2[nH]ccc2c1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCCCN(C)S(C)(=O)=O
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN(S(=O)(=O)C)C.C([O-])([O-])=O.[K+].[K+].OC=1C=C2C=CNC2=CC1>>N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN(S(=O)(=O)C)C
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:22]([O:23][CH2:24][CH2:25][CH2:26][N:27]([CH3:28])[S:29]([CH3:30])(=[O:31])=[O:32])[cH:21][c:20]2[n:19][cH:18][n:17]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][cH:13][cH:14][c:15]2[cH:16]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][cH:13][cH:14][c...
COc1cc2c(Cl)ncnc2cc1OCCCN(C)S(C)(=O)=O.Oc1ccc2[nH]ccc2c1
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCCCN(C)S(C)(=O)=O
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
17
[{"value": 17.0, "product": "N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN(S(=O)(=O)C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 16.9, "product": "N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN(S(=O)(=O)C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
5
HOUR
A mixture of 4-chloro-6-methoxy-7-(3-(N-methyl-N-methylsulphonylamino)propoxy)quinazoline (360 mg, 1.00 mmol), potassium carbonate (215 mg, 1.56 mmol) and 5-hydroxyindole (147 mg, 1.10 mmol) in DMF (8.0 ml) was stirred at 100° C. for 5 hours and allowed to cool to ambient temperature. The solvent was removed by evapora...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
HCl
CN(C)C=O
100
5
COc1cc2c(Cl)ncnc2cc1OCCCN(C)S(C)(=O)=O.Oc1ccc2[nH]ccc2c1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCCCN(C)S(C)(=O)=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-858dd9b659494367896f342f1efb8810
COc1cc2c(Oc3ccc(Br)cc3F)ncnc2cc1OCCCNC(=O)OC(C)(C)C>>COc1cc2c(Oc3ccc(Br)cc3F)ncnc2cc1OCCCN
BrC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)OCCCNC(=O)OC(C)(C)C)C=C1)F>>NCCCOC1=C(C=C2C(=NC=NC2=C1)OC1=C(C=C(C=C1)Br)F)OC
CC(C)(C)OC(=O)[NH:26][CH2:25][CH2:24][CH2:23][O:22][c:21]1[c:3]([O:2][CH3:1])[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]([Br:12])[cH:13][c:14]3[F:15])[n:16][cH:17][n:18][c:19]2[cH:20]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]([Br:12])[cH:13][c:14]3[F:15])[n:16][cH:17][n:18][c:19]2[cH:20]...
COc1cc2c(Oc3ccc(Br)cc3F)ncnc2cc1OCCCNC(=O)OC(C)(C)C
COc1cc2c(Oc3ccc(Br)cc3F)ncnc2cc1OCCCN
null
null
FC(C(=O)O)(F)F
Reduction
Hydrogenolysis of amides/imides/carbamates
3c33dd2a2d355ee5ba0287367e209aa147a39aa00607f0c95fb2bf1ade45d014
c5b5dffe7dd8beebdc1baa8b5b05300a9f7079e65dcfd42ade6f8a77ff09537d
c1ccc(Oc2ncnc3ccccc23)cc1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C:2]-[C:3]>>[C:3]-[C:2]-[NH2;D1;+0:1]
2,093.6
[{"value": 100.0, "product": "NCCCOC1=C(C=C2C(=NC=NC2=C1)OC1=C(C=C(C=C1)Br)F)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 2093.6, "product": "NCCCOC1=C(C=C2C(=NC=NC2=C1)OC1=C(C=C(C=C1)Br)F)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
85
CELSIUS
null
null
4-(4-Bromo-2-fluorophenoxy)-7-(3-(N-tertbutoxycarbonylamino)propoxy)-6-methoxyquinazoline (5.46 g, 0.5 mmol) was taken up in trifluoroacetic acid (75 ml) and heated at 85° C. for 1.5 hours. The solution was allowed to cool and the excess trifluoroacetic acid removed by evaporation. The residue was then treated with aqu...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Primary amine
null
null
c1ccccc1.c1ccc2ncncc2c1
HO-
FC(C(=O)O)(F)F
85
null
COc1cc2c(Oc3ccc(Br)cc3F)ncnc2cc1OCCCNC(=O)OC(C)(C)C>FC(C(=O)O)(F)F>COc1cc2c(Oc3ccc(Br)cc3F)ncnc2cc1OCCCN
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-0c041d7871cb4ad6aa0aa807b48cb8d8
COc1cc2c(Oc3ccc(Br)cc3F)ncnc2cc1OCCCN.CS(=O)(=O)Cl>>COc1cc2c(Oc3ccc(Br)cc3F)ncnc2cc1OCCCNS(C)(=O)=O
NCCCOC1=C(C=C2C(=NC=NC2=C1)OC1=C(C=C(C=C1)Br)F)OC.C(C)N(CC)CC.CS(=O)(=O)Cl>>BrC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)OCCCNS(=O)(=O)C)C=C1)F
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]([Br:12])[cH:13][c:14]3[F:15])[n:16][cH:17][n:18][c:19]2[cH:20][c:21]1[O:22][CH2:23][CH2:24][CH2:25][NH2:26].Cl[S:27]([CH3:28])(=[O:29])=[O:30]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]([Br:12])[cH:13][c:14]3[F:15])[n:16][cH:17]...
COc1cc2c(Oc3ccc(Br)cc3F)ncnc2cc1OCCCN.CS(=O)(=O)Cl
COc1cc2c(Oc3ccc(Br)cc3F)ncnc2cc1OCCCNS(C)(=O)=O
null
null
ClCCl
Acylation
Sulfonamide synthesis (Schotten-Baumann) primary amine
4c44ef6d7646f6ef25dd125d2c32c713d8dcae7c603407faa5f0fb810631670e
8fce8115d8a725afa92eb3910ded29d4c852e5133eba78a425054f41f7142603
c1ccc(Oc2ncnc3ccccc23)cc1
Cl-[S;H0;D4;+0:1](-[C;D1;H3:2])(=[O;D1;H0:3])=[O;D1;H0:4].[C:5]-[C:6]-[NH2;D1;+0:7]>>[C:5]-[C:6]-[NH;D2;+0:7]-[S;H0;D4;+0:1](-[C;D1;H3:2])(=[O;D1;H0:3])=[O;D1;H0:4]
93.1
[{"value": 93.0, "product": "BrC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)OCCCNS(=O)(=O)C)C=C1)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 93.1, "product": "BrC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)OCCCNS(=O)(=O)C)C=C1)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
18
HOUR
A solution of 7-(3-aminopropoxy)-4-(4-bromo-2-fluorophenoxy)-6-methoxyquinazoline (2.71 g, 6.4 mmol) and triethylamine (1.1 ml, 0.80 g, 7.9 mmol) in dichloromethane (15 ml) was treated with a solution of methanesulphonyl chloride (0.53 ml, 0.79 g, 6.9 mmol) in dichloromethane (10 ml) and stirred at ambient temperature,...
10.6084/m9.figshare.5104873.v1
null
Primary amine.Sulfonyl halide
Sulfonamide
null
null
c1ccccc1.c1ccc2ncncc2c1
HCl
ClCCl
null
18
COc1cc2c(Oc3ccc(Br)cc3F)ncnc2cc1OCCCN.CS(=O)(=O)Cl>ClCCl>COc1cc2c(Oc3ccc(Br)cc3F)ncnc2cc1OCCCNS(C)(=O)=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b6a3a8a1e0ab4c4b8bd8377c4c007bcd
CI.COc1cc2c(Oc3ccc(Br)cc3F)ncnc2cc1OCCCNS(C)(=O)=O>>COc1cc2c(Oc3ccc(Br)cc3F)ncnc2cc1OCCCN(C)S(C)(=O)=O
BrC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)OCCCNS(=O)(=O)C)C=C1)F.[H-].[Na+].CI>>BrC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)OCCCN(S(=O)(=O)C)C)C=C1)F
I[CH3:27].[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]([Br:12])[cH:13][c:14]3[F:15])[n:16][cH:17][n:18][c:19]2[cH:20][c:21]1[O:22][CH2:23][CH2:24][CH2:25][NH:26][S:28]([CH3:29])(=[O:30])=[O:31]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]([Br:12])[cH:13][c:14]3[F:15])[n:16][...
CI.COc1cc2c(Oc3ccc(Br)cc3F)ncnc2cc1OCCCNS(C)(=O)=O
COc1cc2c(Oc3ccc(Br)cc3F)ncnc2cc1OCCCN(C)S(C)(=O)=O
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
c6ca050f6d67acb7bc6fc8b4d7848b3f349e4e8db81643cbb6d12b5a34cbf965
9d3dfd18cb6410898a6d822a6d80081d602cf34984cafbfa56b84aa4b38ddbf6
c1ccc(Oc2ncnc3ccccc23)cc1
I-[CH3;D1;+0:1].[C:2]-[C:3]-[NH;D2;+0:4]-[#16:5](-[C;D1;H3:6])(=[O;D1;H0:7])=[O;D1;H0:8]>>[C:2]-[C:3]-[N;H0;D3;+0:4](-[CH3;D1;+0:1])-[#16:5](-[C;D1;H3:6])(=[O;D1;H0:7])=[O;D1;H0:8]
83.6
[{"value": 83.0, "product": "BrC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)OCCCN(S(=O)(=O)C)C)C=C1)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 83.6, "product": "BrC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)OCCCN(S(=O)(=O)C)C)C=C1)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
4-(4-Bromo-2-fluorophenoxy)-6-methoxy-7-(3-(N-methylsulphonylamino)propoxy)quinazoline (1.0 g, 2 mmol) was taken up in DMF (10 ml), treated with sodium hydride (60% dispersion in mineral oil, 0.11 g, 2.7 mmol) and stirred, under nitrogen for 30 minutes. Methyl iodide (0.16 ml, 2.6 mmol) was added and the mixture stirre...
10.6084/m9.figshare.5104873.v1
null
Sulfonamide
Tertiary amine
null
null
c1ccccc1.c1ccc2ncncc2c1
HI
CN(C)C=O
null
0.5
CI.COc1cc2c(Oc3ccc(Br)cc3F)ncnc2cc1OCCCNS(C)(=O)=O>CN(C)C=O>COc1cc2c(Oc3ccc(Br)cc3F)ncnc2cc1OCCCN(C)S(C)(=O)=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-cb33bc7bf02042539bf1ac7c3408d1b0
COc1cc2c(Oc3ccc(Br)cc3F)ncnc2cc1OCCCN(C)S(C)(=O)=O>>COc1cc2c(=O)[nH]cnc2cc1OCCCN(C)S(C)(=O)=O
BrC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)OCCCN(S(=O)(=O)C)C)C=C1)F.C(O)([O-])=O.[Na+]>>COC=1C=C2C(NC=NC2=CC1OCCCN(S(=O)(=O)C)C)=O
Fc1cc(Br)ccc1[O:7][c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:13]([O:14][CH2:15][CH2:16][CH2:17][N:18]([CH3:19])[S:20]([CH3:21])(=[O:22])=[O:23])[cH:12][c:11]2[n:10][cH:9][n:8]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6](=[O:7])[nH:8][cH:9][n:10][c:11]2[cH:12][c:13]1[O:14][CH2:15][CH2:16][CH2:17][N:18]([CH3:19])[S:20]([CH3:21])(...
COc1cc2c(Oc3ccc(Br)cc3F)ncnc2cc1OCCCN(C)S(C)(=O)=O
COc1cc2c(=O)[nH]cnc2cc1OCCCN(C)S(C)(=O)=O
null
null
Cl
Functional Group Interconversion
OtherReaction
2e331e7f987e2f208a7bb6621e9b7dc6ca9e78c94b181dc5496a50196c7c48fe
a99fd2343850f6fbc4a4d7024846a70661aad8ef3f77938589a06d4940f99c06
O=c1[nH]cnc2ccccc12
Br-c1:c:c:c(-[O;H0;D2;+0:1]-[c;H0;D3;+0:2]2:[n;H0;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:2:[c:9]):c(-F):c:1>>[O;H0;D1;+0:1]=[c;H0;D3;+0:2]1:[nH;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]
104
[{"value": 88.0, "product": "COC=1C=C2C(NC=NC2=CC1OCCCN(S(=O)(=O)C)C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 104.0, "product": "COC=1C=C2C(NC=NC2=CC1OCCCN(S(=O)(=O)C)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
4-(4-Bromo-2-fluorophenoxy)-6-methoxy-7-(3-(N-methyl N-methylsulphonylamino)propoxy)quinazoline (4.70 g, 9.1 mmol) was dissolved in 2N aqueous hydrochloric acid solution (85 ml) and heated at reflux for 1 hour. After cooling, the solution was carefully poured into saturated aqueous sodium hydrogen carbonate solution (t...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Ether
null
c1ccccc1.c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1
HF.Br-
Cl
null
0.5
COc1cc2c(Oc3ccc(Br)cc3F)ncnc2cc1OCCCN(C)S(C)(=O)=O>Cl>COc1cc2c(=O)[nH]cnc2cc1OCCCN(C)S(C)(=O)=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3d7a6b98163b4950bbc754421806b1c0
COc1cc2c(=O)[nH]cnc2cc1OCCCN(C)S(C)(=O)=O.O=S(Cl)Cl>>COc1cc2c(Cl)ncnc2cc1OCCCN(C)S(C)(=O)=O
COC=1C=C2C(NC=NC2=CC1OCCCN(S(=O)(=O)C)C)=O.S(=O)(Cl)Cl>>ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN(S(=O)(=O)C)C
O=[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:13]([O:14][CH2:15][CH2:16][CH2:17][N:18]([CH3:19])[S:20]([CH3:21])(=[O:22])=[O:23])[cH:12][c:11]2[n:10][cH:9][nH:8]1.O=S(Cl)[Cl:7]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([Cl:7])[n:8][cH:9][n:10][c:11]2[cH:12][c:13]1[O:14][CH2:15][CH2:16][CH2:17][N:18]([CH3:19])[S:20]([CH3:21])(=[...
COc1cc2c(=O)[nH]cnc2cc1OCCCN(C)S(C)(=O)=O.O=S(Cl)Cl
COc1cc2c(Cl)ncnc2cc1OCCCN(C)S(C)(=O)=O
null
CN(C)C=O
null
Functional Group Interconversion
OtherReaction
3788560e87eee8765e749543914a91a512631307b97fad163ebef894d2a0ea68
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccc2ncncc2c1
Cl-S(=O)-[Cl;H0;D1;+0:1].O=[c;H0;D3;+0:2]1:[nH;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:2]1:[n;H0;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]
80
[{"value": 80.0, "product": "ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN(S(=O)(=O)C)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
6-Methoxy-7-(3-(N-methyl-N-methylsulphonylamino)propoxy)quinazolin-4-one (2.24 g, 6.6 mmol) was taken up in thionyl chloride (25 ml) and treated with DMF (5 drops). The resulting solution was then heated at reflux for 1 hour followed by cooling to ambient temperature. The excess thionyl chloride was removed by evaporat...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1
HCl
CN(C)C=O
null
null
COc1cc2c(=O)[nH]cnc2cc1OCCCN(C)S(C)(=O)=O.O=S(Cl)Cl>CN(C)C=O>COc1cc2c(Cl)ncnc2cc1OCCCN(C)S(C)(=O)=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e6948b52363e4ba1a33f623a63c88dd0
COc1cc2c(Cl)ncnc2cc1OCCCN(C)S(C)(=O)=O.Cc1cc2cc(O)ccc2[nH]1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN(C)S(C)(=O)=O
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN(S(=O)(=O)C)C.C([O-])([O-])=O.[K+].[K+].OC=1C=C2C=C(NC2=CC1)C>>COC=1C=C2C(=NC=NC2=CC1OCCCN(S(=O)(=O)C)C)OC=1C=C2C=C(NC2=CC1)C
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:23]([O:24][CH2:25][CH2:26][CH2:27][N:28]([CH3:29])[S:30]([CH3:31])(=[O:32])=[O:33])[cH:22][c:21]2[n:20][cH:19][n:18]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][c:13]([CH3:14])[cH:15][c:16]2[cH:17]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13](...
COc1cc2c(Cl)ncnc2cc1OCCCN(C)S(C)(=O)=O.Cc1cc2cc(O)ccc2[nH]1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN(C)S(C)(=O)=O
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
35.3
[{"value": 35.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN(S(=O)(=O)C)C)OC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 35.3, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN(S(=O)(=O)C)C)OC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
5
HOUR
A mixture of 4-chloro-6-methoxy-7-(3-(N-methyl-N-methylsulphonylamino)propoxy)quinazoline (360 mg, 1.00 mm ol), (prepared as described for the starting material in Example 152), potassium carbonate (215 mg, 1.56 mmol) and 5-hydroxy-2-methylindole (162 mg, 1.10 mmol) in DMF (8.0 ml) was stirred at 100° C. for 5 hours an...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
HCl
CN(C)C=O
100
5
COc1cc2c(Cl)ncnc2cc1OCCCN(C)S(C)(=O)=O.Cc1cc2cc(O)ccc2[nH]1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN(C)S(C)(=O)=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-8ac9efacedde4d8d88aa60e0f7a4250b
COc1cc2c(Cl)ncnc2cc1OCCCN(C)S(C)(=O)=O.Oc1ccc2cccnc2c1>>COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCCCN(C)S(C)(=O)=O
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN(S(=O)(=O)C)C.C([O-])([O-])=O.[K+].[K+].OC1=CC=C2C=CC=NC2=C1>>COC=1C=C2C(=NC=NC2=CC1OCCCN(S(=O)(=O)C)C)OC1=CC=C2C=CC=NC2=C1
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:23]([O:24][CH2:25][CH2:26][CH2:27][N:28]([CH3:29])[S:30]([CH3:31])(=[O:32])=[O:33])[cH:22][c:21]2[n:20][cH:19][n:18]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[cH:12][cH:13][cH:14][n:15][c:16]2[cH:17]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[cH:12][cH:13][cH...
COc1cc2c(Cl)ncnc2cc1OCCCN(C)S(C)(=O)=O.Oc1ccc2cccnc2c1
COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCCCN(C)S(C)(=O)=O
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1cnc2cc(Oc3ncnc4ccccc34)ccc2c1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#7;a:9]:[c:10]:[c:11]:[c:12](-[OH;D1;+0:13]):[c:14]>>[#7;a:9]:[c:10]:[c:11]:[c:12](-[O;H0;D2;+0:13]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:14]
63
[{"value": 63.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN(S(=O)(=O)C)C)OC1=CC=C2C=CC=NC2=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 62.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN(S(=O)(=O)C)C)OC1=CC=C2C=CC=NC2=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
2
HOUR
A mixture of 4-chloro-6-methoxy-7-(3-(N-methyl-N-methylsulphonylamino)propoxy)quinazoline (150 mg, 0.42 mmol), (prepared as described for the starting material in Example 152), potassium carbonate (90 mg, 0.63 mmol) and 7hydroxyquinoline (67 mg, 0.46 mmol) in DMF (5.0 ml) was stirred at 100° C. for 2 hours and allowed ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncccc2c1.c1ccc2ncncc2c1
HCl
CN(C)C=O
100
2
COc1cc2c(Cl)ncnc2cc1OCCCN(C)S(C)(=O)=O.Oc1ccc2cccnc2c1>CN(C)C=O>COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCCCN(C)S(C)(=O)=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-201b31eda4c34809b27034be8982938b
COc1cc2c(Cl)ncnc2cc1OCCCN(C)S(C)(=O)=O.Cc1ccnc2cc(O)ccc12>>COc1cc2c(Oc3ccc4c(C)ccnc4c3)ncnc2cc1OCCCN(C)S(C)(=O)=O
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN(S(=O)(=O)C)C.C([O-])([O-])=O.[K+].[K+].OC1=CC=C2C(=CC=NC2=C1)C>>COC=1C=C2C(=NC=NC2=CC1OCCCN(S(=O)(=O)C)C)OC1=CC=C2C(=CC=NC2=C1)C
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:24]([O:25][CH2:26][CH2:27][CH2:28][N:29]([CH3:30])[S:31]([CH3:32])(=[O:33])=[O:34])[cH:23][c:22]2[n:21][cH:20][n:19]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[c:12]([CH3:13])[cH:14][cH:15][n:16][c:17]2[cH:18]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[c:12]([...
COc1cc2c(Cl)ncnc2cc1OCCCN(C)S(C)(=O)=O.Cc1ccnc2cc(O)ccc12
COc1cc2c(Oc3ccc4c(C)ccnc4c3)ncnc2cc1OCCCN(C)S(C)(=O)=O
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1cnc2cc(Oc3ncnc4ccccc34)ccc2c1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#7;a:9]:[c:10]:[c:11]:[c:12](-[OH;D1;+0:13]):[c:14]>>[#7;a:9]:[c:10]:[c:11]:[c:12](-[O;H0;D2;+0:13]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:14]
42
[{"value": 42.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN(S(=O)(=O)C)C)OC1=CC=C2C(=CC=NC2=C1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 41.4, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN(S(=O)(=O)C)C)OC1=CC=C2C(=CC=NC2=C1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
2
HOUR
A mixture of 4-chloro-6-methoxy-7-(3-(N-methyl-N-methylsulphonylamino)propoxy)quinazoline (150 mg, 0.42 mmol), (prepared as described for the starting material in Example 152), potassium carbonate (90 mg, 0.63 mmol) and 7-hydroxy-4-methylquinoline (71 mg, 0.46 mmol), (Chem. Berich. 1967, 100, 2077), in DMF (5.0 ml) was...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncccc2c1.c1ccc2ncncc2c1
HCl
CN(C)C=O
100
2
COc1cc2c(Cl)ncnc2cc1OCCCN(C)S(C)(=O)=O.Cc1ccnc2cc(O)ccc12>CN(C)C=O>COc1cc2c(Oc3ccc4c(C)ccnc4c3)ncnc2cc1OCCCN(C)S(C)(=O)=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e66ac03e03f84c75ad3ea3256f26e11f
COc1ccc2cc(F)c(=O)[nH]c2c1.O=S(Cl)Cl>>COc1ccc2cc(F)c(Cl)nc2c1
FC=1C(NC2=CC(=CC=C2C1)OC)=O.S(=O)(Cl)Cl>>ClC1=NC2=CC(=CC=C2C=C1F)OC
O=[c:10]1[c:8]([F:9])[cH:7][c:6]2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:14][c:13]2[nH:12]1.O=S(Cl)[Cl:11]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[cH:7][c:8]([F:9])[c:10]([Cl:11])[n:12][c:13]2[cH:14]1
COc1ccc2cc(F)c(=O)[nH]c2c1.O=S(Cl)Cl
COc1ccc2cc(F)c(Cl)nc2c1
null
CN(C)C=O
null
Functional Group Interconversion
OtherReaction
608f63cb1f4eb5f8ff4f6128056e651e12d8905ddec242decf5bdb71da52a2d7
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccc2ncccc2c1
Cl-S(=O)-[Cl;H0;D1;+0:1].O=[c;H0;D3;+0:2]1:[nH;D2;+0:3]:[c:4](:[c:5]):[c:6]:[c:7]:[c:8]:1-[F;D1;H0:9]>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:2]1:[n;H0;D2;+0:3]:[c:4](:[c:5]):[c:6]:[c:7]:[c:8]:1-[F;D1;H0:9]
97
[{"value": 97.0, "product": "ClC1=NC2=CC(=CC=C2C=C1F)OC", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
3-Fluoro-7-methoxyquinol-2(1H)-one (300 mg, 1.55 mmol), (prepared as in Tetrahedron, Vol. 52, No. 9, pp. 3223–3228, 1996), was dissolved in thionyl chloride (3 ml), treated with DMF (1 drop) and heated at reflux for 1 hour. The excess thionyl chloride was removed by evaporation and the residue azeotroped with toluene (...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1cnc2ccccc2c1
c1ccc2ncccc2c1
c1ccc2ncccc2c1
HCl
CN(C)C=O
null
null
COc1ccc2cc(F)c(=O)[nH]c2c1.O=S(Cl)Cl>CN(C)C=O>COc1ccc2cc(F)c(Cl)nc2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-47c36ea540f04f7688920621e4f1f72a
COc1ccc2cc(F)c(Cl)nc2c1>>COc1ccc2cc(F)cnc2c1
ClC1=NC2=CC(=CC=C2C=C1F)OC.C(C)N(CC)CC>>FC=1C=NC2=CC(=CC=C2C1)OC
Cl[c:10]1[c:8]([F:9])[cH:7][c:6]2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:13][c:12]2[n:11]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[cH:7][c:8]([F:9])[cH:10][n:11][c:12]2[cH:13]1
COc1ccc2cc(F)c(Cl)nc2c1
COc1ccc2cc(F)cnc2c1
null
[Pd]
C(C)O
Functional Group Interconversion
Aromatic dehalogenation
9d8b09641537c9b7067a6060cf65ecd110c7af466a7b229ce3601533f966554e
56de34d4a44cb25d9380269ee5e138b0f24b40a3a0db22c5508049dc775a861f
c1ccc2ncccc2c1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4](-[F;D1;H0:5]):[c:6]>>[F;D1;H0:5]-[c:4](:[c:6]):[cH;D2;+0:1]:[#7;a:2]:[c:3]
54
[{"value": 54.0, "product": "FC=1C=NC2=CC(=CC=C2C1)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 49.9, "product": "FC=1C=NC2=CC(=CC=C2C1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
24
HOUR
A mixture of 2-chloro-3-fluoro-7-methoxyquinoline (310 mg, 1.47 mmol), triethylamine (310 mg, 0.4 ml, 3.07 mmol) and 10% palladium on activated charcoal (50 mg) in dry ethanol (5 ml) was stirred under hydrogen gas at ambient temperature for 24 hours. The mixture was then filtered through celite. The celite was washed w...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
null
c1ccc2ncccc2c1
c1ccc2ncccc2c1
c1ccc2ncccc2c1
Other
[Pd].C(C)O
null
24
COc1ccc2cc(F)c(Cl)nc2c1>[Pd].C(C)O>COc1ccc2cc(F)cnc2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-76e7e2024c9c4fb4b22242708b9a260b
COc1ccc2cc(F)cnc2c1>>Oc1ccc2cc(F)cnc2c1
CO.FC=1C=NC2=CC(=CC=C2C1)OC.B(Br)(Br)Br>>FC=1C=NC2=CC(=CC=C2C1)O
C[O:1][c:2]1[cH:3][cH:4][c:5]2[cH:6][c:7]([F:8])[cH:9][n:10][c:11]2[cH:12]1>>[OH:1][c:2]1[cH:3][cH:4][c:5]2[cH:6][c:7]([F:8])[cH:9][n:10][c:11]2[cH:12]1
COc1ccc2cc(F)cnc2c1
Oc1ccc2cc(F)cnc2c1
null
null
ClCCl
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2ncccc2c1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]:[c:2](-[OH;D1;+0:1]):[c:3]
null
[]
null
null
24
HOUR
3-Fluoro-7-methoxyquinoline (130 mg, 0.74 mmol) was taken up in dichloromethane (2 ml) under nitrogen and treated with boron tribromide (4 ml of a 11.0M solution of in dichloromethane). The reaction mixture was stirred for 24 hours at ambient temperature followed by quenching the reaction by the slow addition of excess...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1ccc2ncccc2c1
Other
ClCCl
null
24
COc1ccc2cc(F)cnc2c1>ClCCl>Oc1ccc2cc(F)cnc2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-14533589759940e8bcf11c574ca1a8a0
COc1ccc2cc(F)c(Cl)nc2c1>>COc1ccc2cc(F)c(C)nc2c1
C[Mg]Br.ClC1=NC2=CC(=CC=C2C=C1F)OC.[Cl-].[NH4+].[OH-].[Na+]>>FC=1C(=NC2=CC(=CC=C2C1)OC)C
Cl[c:10]1[c:8]([F:9])[cH:7][c:6]2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:14][c:13]2[n:12]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[cH:7][c:8]([F:9])[c:10]([CH3:11])[n:12][c:13]2[cH:14]1
COc1ccc2cc(F)c(Cl)nc2c1
COc1ccc2cc(F)c(C)nc2c1
null
[Cu]Br
C1CCOC1
Functional Group Interconversion
OtherReaction
9d8b09641537c9b7067a6060cf65ecd110c7af466a7b229ce3601533f966554e
56de34d4a44cb25d9380269ee5e138b0f24b40a3a0db22c5508049dc775a861f
c1ccc2ncccc2c1
Cl-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4](-[F;D1;H0:5]):[c:6]>>[C;D1;H3:7]-[c;H0;D3;+0:1](:[#7;a:2]:[c:3]):[c:4](-[F;D1;H0:5]):[c:6]
91
[{"value": 91.0, "product": "FC=1C(=NC2=CC(=CC=C2C1)OC)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 88.9, "product": "FC=1C(=NC2=CC(=CC=C2C1)OC)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
-78
CELSIUS
1
HOUR
2-Chloro-3-fluoro-7-methoxyquinoline (210 mg, 1 mmol), (prepared as described for the starting material in Example 157), in anhydrous THF (1 ml) was added to a mixture of copper(I)bromide (570 mg, 4.0 mmol) and methylmagnesium bromide (3.0M solution in diethyl ether, 2.7 ml, 8 mmol) in anhydrous THF (20 ml) at −78° C. ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
null
c1ccc2ncccc2c1
c1ccc2ncccc2c1
c1ccc2ncccc2c1
null
[Cu]Br.C1CCOC1
-78
1
COc1ccc2cc(F)c(Cl)nc2c1>[Cu]Br.C1CCOC1>COc1ccc2cc(F)c(C)nc2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-c0f5554e13f848dbb8c550eef8f5d8a3
COc1ccc2cc(F)c(C)nc2c1>>Cc1nc2cc(O)ccc2cc1F
CO.FC=1C(=NC2=CC(=CC=C2C1)OC)C.B(Br)(Br)Br>>FC=1C(=NC2=CC(=CC=C2C1)O)C
C[O:7][c:6]1[cH:5][c:4]2[n:3][c:2]([CH3:1])[c:12]([F:13])[cH:11][c:10]2[cH:9][cH:8]1>>[CH3:1][c:2]1[n:3][c:4]2[cH:5][c:6]([OH:7])[cH:8][cH:9][c:10]2[cH:11][c:12]1[F:13]
COc1ccc2cc(F)c(C)nc2c1
Cc1nc2cc(O)ccc2cc1F
null
null
ClCCl
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2ncccc2c1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]:[c:2](-[OH;D1;+0:1]):[c:3]
null
[]
null
null
24
HOUR
3-Fluoro-7-methoxy-2-methylquinoline (0.16 g, 0.85 mmol) was taken up in dichloromethane (4 ml) under nitrogen and treated with boron tribromide solution (4 ml of a 11.0M solution in dichloromethane, 4.0 mmol). The reaction was stirred for 24 hours at ambient temperature followed by the slow addition of excess methanol...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1ccc2ncccc2c1
Other
ClCCl
null
24
COc1ccc2cc(F)c(C)nc2c1>ClCCl>Cc1nc2cc(O)ccc2cc1F
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-918c932a36024ae5be2f60ed5afdc35b
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1ccc2cccnc2c1>>COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCCCN1CCCCC1
[OH-].[Na+].ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1.C([O-])([O-])=O.[K+].[K+].OC1=CC=C2C=CC=NC2=C1>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCCC1)OC1=CC=C2C=CC=NC2=C1
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:23]([O:24][CH2:25][CH2:26][CH2:27][N:28]3[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]3)[cH:22][c:21]2[n:20][cH:19][n:18]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[cH:12][cH:13][cH:14][n:15][c:16]2[cH:17]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[cH:12][cH:13][cH...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1ccc2cccnc2c1
COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCCCN1CCCCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1cnc2cc(Oc3ncnc4cc(OCCCN5CCCCC5)ccc34)ccc2c1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#7;a:9]:[c:10]:[c:11]:[c:12](-[OH;D1;+0:13]):[c:14]>>[#7;a:9]:[c:10]:[c:11]:[c:12](-[O;H0;D2;+0:13]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:14]
52
[{"value": 52.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCCC1)OC1=CC=C2C=CC=NC2=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 51.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCCC1)OC1=CC=C2C=CC=NC2=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
4
HOUR
A mixture of 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (400 mg, 1.19 mmol), (prepared as described for the starting material in Example 67), potassium carbonate (255 mg, 1.84 mmol) and 7-hydroxyquinoline (180 mg, 1.32 mmol) in DMF (10 ml) was stirred at 100° C. for 4 hours and then allowed to cool to ambien...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
CN(C)C=O
100
4
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1ccc2cccnc2c1>CN(C)C=O>COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCCCN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a947657169974ce492a4995d6fbad691
COc1cc2c(Cl)ncnc2cc1OCCCN(C)S(C)(=O)=O.Cc1[nH]c2ccc(O)cc2c1C>>COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCCCN(C)S(C)(=O)=O
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN(S(=O)(=O)C)C.C([O-])([O-])=O.[K+].[K+].CC=1NC2=CC=C(C=C2C1C)O>>CC=1NC2=CC=C(C=C2C1C)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN(S(=O)(=O)C)C
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:24]([O:25][CH2:26][CH2:27][CH2:28][N:29]([CH3:30])[S:31]([CH3:32])(=[O:33])=[O:34])[cH:23][c:22]2[n:21][cH:20][n:19]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][c:13]([CH3:14])[c:15]([CH3:16])[c:17]2[cH:18]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:1...
COc1cc2c(Cl)ncnc2cc1OCCCN(C)S(C)(=O)=O.Cc1[nH]c2ccc(O)cc2c1C
COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCCCN(C)S(C)(=O)=O
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
42
[{"value": 42.0, "product": "CC=1NC2=CC=C(C=C2C1C)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN(S(=O)(=O)C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 41.5, "product": "CC=1NC2=CC=C(C=C2C1C)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN(S(=O)(=O)C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
5
HOUR
A mixture of 4-chloro-6-methoxy-7-(3-(N-methyl-N-methylsulphonylamino)propoxy)quinazoline (360 mg, 1.00 mmol), (prepared as described for the starting material in Example 152), potassium carbonate (215 mg, 1.56 mmol) and 2,3-dimethyl-5-hydroxyindole (177 mg, 1.10 mmol), (Arch. Pharm. 1972, 305, 159), in DMF (8.0 ml) wa...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
HCl
CN(C)C=O
100
5
COc1cc2c(Cl)ncnc2cc1OCCCN(C)S(C)(=O)=O.Cc1[nH]c2ccc(O)cc2c1C>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCCCN(C)S(C)(=O)=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b33bc77474b14b988eedcc8eb51a757b
BrCC1CO1.C1COCCN1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC(O)CN1CCOCC1
OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC.C([O-])([O-])=O.[K+].[K+].C(Br)C1CO1.N1CCOCC1>>OC(COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)CN1CCOCC1
Br[CH2:25][CH:26]1[O:27][CH2:28]1.[NH:29]1[CH2:30][CH2:31][O:32][CH2:33][CH2:34]1.[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[cH:15][c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[OH:24]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c...
BrCC1CO1.C1COCCN1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC(O)CN1CCOCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
9e8854a5ecfdc8b15022d98dbe1f2eae1fc393a2fececee6fd576a5ba2e5b3ae
eb518202353ad700a277551600b1491d8d2c7644482abd04ae296bc3a44ea97b
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCOCC3)cc2n1
Br-[CH2;D2;+0:1]-[C:2]1-[CH2;D2;+0:3]-[O;H0;D2;+0:4]-1.[#7;a:5]:[c:6]:[c:7]:[c:8](-[OH;D1;+0:9]):[c:10].[#8:11]1-[C:12]-[C:13]-[NH;D2;+0:14]-[C:15]-[C:16]-1>>[#7;a:5]:[c:6]:[c:7]:[c:8](-[O;H0;D2;+0:9]-[CH2;D2;+0:1]-[C:2](-[OH;D1;+0:4])-[CH2;D2;+0:3]-[N;H0;D3;+0:14]1-[C:13]-[C:12]-[#8:11]-[C:16]-[C:15]-1):[c:10]
45.6
[{"value": 27.0, "product": "OC(COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)CN1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 45.6, "product": "OC(COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)CN1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
2
HOUR
A mixture of 7-hydroxy-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (322 mg, 1.00 mmol), (prepared as described in Example 49), potassium carbonate (414 mg, 3.00 mmol) and epibromohydrin (274 mg, 2.00 mmol) in DMF (7.0 ml) was stirred at 60° C. for 2 hours and allowed to cool to ambient temperature. The solvent was r...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ether.Aromatic alcohol.Secondary amine
Ether.Secondary alcohol.Tertiary amine
C1CO1.C1COCCN1
C1COCC[NH]1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1COCC[NH]1
HBr
CN(C)C=O
60
2
BrCC1CO1.C1COCCN1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC(O)CN1CCOCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-750ad2dfc2884ea3999ef546c21a1e4d
C1CCNCC1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CO1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC(O)CN1CCCCC1
O1C(COC2=C(C=C3C(=NC=NC3=C2)OC=2C=C3C=C(NC3=CC2)C)OC)C1.N1CCCCC1>>OC(COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)CN1CCCCC1
[NH:29]1[CH2:30][CH2:31][CH2:32][CH2:33][CH2:34]1.[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[cH:15][c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[O:24][CH2:25][CH:26]1[O:27][CH2:28]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:1...
C1CCNCC1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CO1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC(O)CN1CCCCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Ring opening of epoxide with amine
c5753b22446d1ae5dcee7a30af0c7f96061ec363349faf28c9adeaca5e033c6d
97e758d6c4c8255d25541eb6c6a6f62e7dc30829ea162ca3392731efabc98a65
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCCCC3)cc2n1
[C:1]-[C:2]-[NH;D2;+0:3]-[C:4]-[C:5].[C:6]-[C:7]1-[CH2;D2;+0:8]-[O;H0;D2;+0:9]-1>>[C:6]-[C:7](-[OH;D1;+0:9])-[CH2;D2;+0:8]-[N;H0;D3;+0:3](-[C:2]-[C:1])-[C:4]-[C:5]
65
[{"value": 65.0, "product": "OC(COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)CN1CCCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 64.1, "product": "OC(COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)CN1CCCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
70
CELSIUS
null
null
A mixture of 7-(2,3-epoxypropoxy)-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (100 mg, 0.27 mmol) and piperidine (79ul, 0.8 mmol) in DMF (4 ml) was heated at 70° C. for 24 hours. The solvent was removed by evaporation and the residue was recrystallised from acetonitrile. The solid was filtered, washed with diethyl e...
10.6084/m9.figshare.5104873.v1
null
Ether.Secondary amine
Secondary alcohol.Tertiary amine
C1CCNCC1.C1CO1
C1CC[NH]CC1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
null
CN(C)C=O
70
null
C1CCNCC1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CO1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC(O)CN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-0bf01e89cf524f49a043d2019db3ed3b
BrCC1CO1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CO1
OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC.C([O-])([O-])=O.[K+].[K+].C(Br)C1CO1>>O1C(COC2=C(C=C3C(=NC=NC3=C2)OC=2C=C3C=C(NC3=CC2)C)OC)C1
Br[CH2:25][CH:26]1[CH2:27][O:28]1.[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[cH:15][c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[OH:24]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[cH:15][c:16]4[cH:17]3)[n:18][cH:1...
BrCC1CO1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CO1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCC3CO3)cc2n1
Br-[CH2;D2;+0:1]-[C:2]1-[#8:3]-[C:4]-1.[#7;a:5]:[c:6]:[c:7]:[c:8](-[OH;D1;+0:9]):[c:10]>>[#7;a:5]:[c:6]:[c:7]:[c:8](-[O;H0;D2;+0:9]-[CH2;D2;+0:1]-[C:2]1-[#8:3]-[C:4]-1):[c:10]
89
[{"value": 89.0, "product": "O1C(COC2=C(C=C3C(=NC=NC3=C2)OC=2C=C3C=C(NC3=CC2)C)OC)C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 88.5, "product": "O1C(COC2=C(C=C3C(=NC=NC3=C2)OC=2C=C3C=C(NC3=CC2)C)OC)C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
2
HOUR
A mixture of 7-hydroxy-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (1.89 g, 5.90 mmol), (prepared as described in Example 49), potassium carbonate (2.43 g, 17.6 mmol) and epibromohydrin (1.61 g, 11.7 mmol) in DMF (40 ml) was stirred at 60° C. for 2 hours and allowed to cool to ambient temperature. The insoluble inor...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CO1
HBr
CN(C)C=O
60
2
BrCC1CO1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CO1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-ed7e7184230d4f159c3035aff7748ca7
C1CCNC1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CO1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC(O)CN1CCCC1
O1C(COC2=C(C=C3C(=NC=NC3=C2)OC=2C=C3C=C(NC3=CC2)C)OC)C1.N1CCCC1>>OC(COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)CN1CCCC1
[NH:29]1[CH2:30][CH2:31][CH2:32][CH2:33]1.[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[cH:15][c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[O:24][CH2:25][CH:26]1[O:27][CH2:28]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:...
C1CCNC1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CO1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC(O)CN1CCCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Ring opening of epoxide with amine
76b1810a18be65e42ea157c2729971f505df73ec247c72e2192a1e56ead5967f
97e758d6c4c8255d25541eb6c6a6f62e7dc30829ea162ca3392731efabc98a65
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCCC3)cc2n1
[C:1]-[C:2]1-[CH2;D2;+0:3]-[O;H0;D2;+0:4]-1.[C:5]1-[C:6]-[C:7]-[C:8]-[NH;D2;+0:9]-1>>[C:1]-[C:2](-[OH;D1;+0:4])-[CH2;D2;+0:3]-[N;H0;D3;+0:9]1-[C:5]-[C:6]-[C:7]-[C:8]-1
37
[{"value": 37.0, "product": "OC(COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)CN1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 36.3, "product": "OC(COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)CN1CCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
70
CELSIUS
null
null
A mixture of 7-(2,3-epoxypropoxy)-6-methoxy-4-(2-methylindol-5-yloxy) quinazoline (100 mg, 0.27 mmol), (prepared as described for the starting material in Example 162), and pyrrolidine (67 ul, 0.8 mmol) in DMF (4 ml) was heated at 70° C. for 24 hours. The solvent was removed by evaporation and the residue purified by s...
10.6084/m9.figshare.5104873.v1
null
Ether.Secondary amine
Secondary alcohol.Tertiary amine
C1CCNC1.C1CO1
C1CC[NH]C1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]C1
null
CN(C)C=O
70
null
C1CCNC1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CO1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC(O)CN1CCCC1