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-827aca2c99d04cc1a044b4a8bf2652ae
COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1.Oc1ccc2[nH]ccc2c1F>>COc1cc2c(Oc3ccc4[nH]ccc4c3F)ncnc2cc1OCCCN1CCN(C)CC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C.FC1=C2C=CNC2=CC=C1O.C([O-])([O-])=O.[K+].[K+]>>FC1=C2C=CNC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(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][N:31]([CH3:32])[CH2:33][CH2:34]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][cH:13][cH:14][c:15]2[c:16]1[F:17]>>[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...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1.Oc1ccc2[nH]ccc2c1F
COc1cc2c(Oc3ccc4[nH]ccc4c3F)ncnc2cc1OCCCN1CCN(C)CC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCNCC3)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]
42.2
[{"value": 42.0, "product": "FC1=C2C=CNC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 42.2, "product": "FC1=C2C=CNC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
95
CELSIUS
3
HOUR
A mixture of 4-chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline (232 mg, 0.662 mmol), (prepared as described for the starting material in Examples 176 or 244), and 4-fluoro-5-hydroxyindole (120 mg, 0.794 mmol), (prepared as described for the starting material in Example 242), in DMF (3 ml) containing p...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1C[NH]CC[NH]1
HCl
CN(C)C=O
95
3
COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1.Oc1ccc2[nH]ccc2c1F>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]ccc4c3F)ncnc2cc1OCCCN1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-f0a21121369d4d2e83e725978514d809
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCNCC1.ClCCN1CCCC1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCN(CCN2CCCC2)CC1
COC=1C=C2C(=NC=NC2=CC1OCC1CCNCC1)OC=1C=C2C=C(NC2=CC1)C.ClCCN1CCCC1.C([O-])([O-])=O.[Na+].[Na+].[I-].[K+]>>COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)CCN1CCCC1)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[O:24][CH2:25][CH:26]1[CH2:27][CH2:28][NH:29][CH2:37][CH2:38]1.Cl[CH2:30][CH2:31][N:32]1[CH2:33][CH2:34][CH2:35][CH2:36]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:...
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCNCC1.ClCCN1CCCC1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCN(CCN2CCCC2)CC1
null
null
CO
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
0240b8450ff2c489d02f5f0d90bc953079d7a3ab239d35a03f26392fc248b4ef
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCC3CCN(CCN4CCCC4)CC3)cc2n1
Cl-[CH2;D2;+0:1]-[C:2]-[#7:3].[C:4]-[C:5]-[NH;D2;+0:6]-[C:7]-[C:8]>>[#7:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:6](-[C:5]-[C:4])-[C:7]-[C:8]
20
[{"value": 20.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)CCN1CCCC1)OC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 13.8, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)CCN1CCCC1)OC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
50
CELSIUS
null
null
A mixture of 6-methoxy-4-(2-methylindol-5-yloxy)-7-(piperidin-4-ylmethoxy)quinazoline (600 mg, 1.43 mmol), (prepared as described in Example 70), 1-(2-chloroethyl)-pyrrolidine (292 mg, 1.72 mmol) in methanol (14 ml) containing sodium carbonate (262 mg, 4.3 mmol) and potassium iodide (48 mg, 0.29 mmol) was heated at 50°...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1CCNCC1
C1CC[NH]CC1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1.C1CC[NH]C1
HCl
CO
50
null
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCNCC1.ClCCN1CCCC1>CO>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCN(CCN2CCCC2)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-fff12c083f2d4e2ab369ffc87bd1d18f
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Oc1cc2cc[nH]c2cc1F>>COc1cc2c(Oc3cc4cc[nH]c4cc3F)ncnc2cc1OCCCN1CCOCC1
O.ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1.FC1=C(C=C2C=CNC2=C1)O.C([O-])([O-])=O.[K+].[K+]>>FC1=C(C=C2C=CNC2=C1)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: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][c:10]2[cH:11][cH:12][nH:13][c:14]2[cH:15][c:16]1[F:17]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][c:10]4[cH:11][cH:12][nH:13][c:14]...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Oc1cc2cc[nH]c2cc1F
COc1cc2c(Oc3cc4cc[nH]c4cc3F)ncnc2cc1OCCCN1CCOCC1
null
null
CN(C)C=O
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]
41
[{"value": 41.0, "product": "FC1=C(C=C2C=CNC2=C1)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 37.4, "product": "FC1=C(C=C2C=CNC2=C1)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
90
CELSIUS
null
null
A mixture of 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (110 mg, 0.325 mmol), (prepared as described for the starting material in Example 1), and 6-fluoro-5-hydroxyindole (59 mg, 0.39 mmol), (prepared as described for the starting material in Example 242), in DMF (1.8 ml) containing potassium carbonate (67 m...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1COCC[NH]1
HCl
CN(C)C=O
90
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Oc1cc2cc[nH]c2cc1F>CN(C)C=O>COc1cc2c(Oc3cc4cc[nH]c4cc3F)ncnc2cc1OCCCN1CCOCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b8614837fc174298adee985ee2d1dda5
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1O.OCCN1CCOCC1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCCN1CCOCC1
N(=NC(=O)OCC)C(=O)OCC.OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.OCCN1CCOCC1>>N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCN1CCOCC1
[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].O[CH2:24][CH2:25][N:26]1[CH2:27][CH2:28][O:29][CH2:30][CH2:31]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...
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1O.OCCN1CCOCC1
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCCN1CCOCC1
null
null
C(Cl)Cl
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCN3CCOCC3)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]
55
[{"value": 55.0, "product": "N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCN1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 54.3, "product": "N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCN1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
10
CELSIUS
3
HOUR
To a solution of 7-hydroxy-4-(indol-5-yloxy)-6-methoxyquinazoline (183 mg, 0.6 mmol), (prepared as described for the starting material in Example 107), triphenylphosphine (235 mg, 0.89 mmol) and 4-(2-hydroxyethyl)morpholine (93 mg, 0.72 mmol) in methylene chloride (4 ml) cooled at 10° C. was added diethyl azodicarboxyl...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1COCC[NH]1
HO-
C(Cl)Cl
10
3
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1O.OCCN1CCOCC1>C(Cl)Cl>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCCN1CCOCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-179d12d1cebe48639e155c74702b58c4
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OC[C@@H](CN1CCCC1)OC(C)=O>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OC[C@H](O)CN1CCCC1
C(C)(=O)O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C(=C2C=C(NC2=CC1)C)F)OC)CN1CCCC1.N>>O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C(=C2C=C(NC2=CC1)C)F)OC)CN1CCCC1
CC(=O)[O:28][C@@H:27]([CH2:26][O:25][c:24]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[c:17]3[F:18])[n:19][cH:20][n:21][c:22]2[cH:23]1)[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]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12...
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OC[C@@H](CN1CCCC1)OC(C)=O
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OC[C@H](O)CN1CCCC1
null
null
CO
Reduction
Hydrolysis or Hydrogenolysis of Carboxylic Esters or Thioesters
d7acfb2397f2b5b2a83b3bebf3698d6d984dd716982297f62a944222c79ce234
19dd58e0f83625e74b4b1375d88cb4c813ee60f593d812516d14eafc4ab68dc7
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCCC3)cc2n1
C-C(=O)-[O;H0;D2;+0:1]-[C:2](-[C:3])-[C:4]>>[C:3]-[C:2](-[C:4])-[OH;D1;+0:1]
75
[{"value": 75.0, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C(=C2C=C(NC2=CC1)C)F)OC)CN1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 74.6, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C(=C2C=C(NC2=CC1)C)F)OC)CN1CCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of (2R)-7-(2-acetoxy-3-(pyrrolidin-1-yl)propoxy)-4-(4-fluoro-2-methylindol-5-yloxy)-6-methoxyquinazoline (570 mg, 1.12 mmol) in methanol saturated with ammonia (7 ml) was stirred overnight at ambient temperature. The volatiles were removed under vacuum and the residue was purified by column chromatography el...
10.6084/m9.figshare.5104873.v1
null
Ester
Secondary alcohol
null
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]C1
HO-
CO
null
null
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OC[C@@H](CN1CCCC1)OC(C)=O>CO>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OC[C@H](O)CN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-2a5cda6931414ca185c1b2bb674b7242
CC(=O)OC(C)=O.COc1cc2c(=O)[nH]cnc2cc1OC[C@H](O)CN1CCCC1>>COc1cc2c(=O)[nH]cnc2cc1OC[C@@H](CN1CCCC1)OC(C)=O
O[C@@H](COC1=C(C=C2C(NC=NC2=C1)=O)OC)CN1CCCC1.C(C)(=O)OC(C)=O.O>>C(C)(=O)O[C@@H](COC1=C(C=C2C(NC=NC2=C1)=O)OC)CN1CCCC1
CC(=O)O[C:24]([CH3:25])=[O:26].[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][C@@H:16]([CH2:17][N:18]1[CH2:19][CH2:20][CH2:21][CH2:22]1)[OH:23]>>[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][C@@H:16]([CH2:17][N:18]1[CH2...
CC(=O)OC(C)=O.COc1cc2c(=O)[nH]cnc2cc1OC[C@H](O)CN1CCCC1
COc1cc2c(=O)[nH]cnc2cc1OC[C@@H](CN1CCCC1)OC(C)=O
null
null
null
Acylation
Transesterification
a7ad17dd333d7246e42d4632a0a7042db0b0d3b7f2adb7cdb2c46498a22ac4db
c98fee24664998fb42388f3a4804f79d763c5043c4f5565ea3b46913e3a86a6e
O=c1[nH]cnc2cc(OCCCN3CCCC3)ccc12
C-C(=O)-O-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].[C:4]-[C:5](-[C:6])-[OH;D1;+0:7]>>[C:4]-[C:5](-[C:6])-[O;H0;D2;+0:7]-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3]
65.6
[{"value": 65.0, "product": "C(C)(=O)O[C@@H](COC1=C(C=C2C(NC=NC2=C1)=O)OC)CN1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 65.6, "product": "C(C)(=O)O[C@@H](COC1=C(C=C2C(NC=NC2=C1)=O)OC)CN1CCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
A mixture of (2R)-7-(2-hydroxy-3-(pyrrolidin-1-yl)propoxy)-6-methoxy-3,4-dihydroquinazolin-4-one (803 mg, 2.51 mmol) in acetic anhydride (1.2 ml, 12.5 mmol) was stirred at ambient temperature for 1 hour. Water (360 μl, 20 mmol) was added and stirring was continued for 90 minutes. The mixture was partitioned between aqu...
10.6084/m9.figshare.5104873.v1
null
Anhydride.Secondary alcohol
Ester
null
null
c1ccc2ncncc2c1.C1CC[NH]C1
HO-
null
null
1
CC(=O)OC(C)=O.COc1cc2c(=O)[nH]cnc2cc1OC[C@H](O)CN1CCCC1>>COc1cc2c(=O)[nH]cnc2cc1OC[C@@H](CN1CCCC1)OC(C)=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-47e0365b1812489482b8aa55a39d018c
COc1cc2c(=O)[nH]cnc2cc1OC[C@@H](CN1CCCC1)OC(C)=O.O=S(Cl)Cl>>COc1cc2c(Cl)ncnc2cc1OC[C@@H](CN1CCCC1)OC(C)=O
C(C)(=O)O[C@@H](COC1=C(C=C2C(NC=NC2=C1)=O)OC)CN1CCCC1.S(=O)(Cl)Cl>>C(C)(=O)O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)Cl)OC)CN1CCCC1
O=[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:13]([O:14][CH2:15][C@@H:16]([CH2:17][N:18]3[CH2:19][CH2:20][CH2:21][CH2:22]3)[O:23][C:24]([CH3:25])=[O:26])[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][C@@H:16]([CH2:17][N:18]1[C...
COc1cc2c(=O)[nH]cnc2cc1OC[C@@H](CN1CCCC1)OC(C)=O.O=S(Cl)Cl
COc1cc2c(Cl)ncnc2cc1OC[C@@H](CN1CCCC1)OC(C)=O
null
CN(C)C=O
null
Functional Group Interconversion
OtherReaction
3788560e87eee8765e749543914a91a512631307b97fad163ebef894d2a0ea68
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ncc2ccc(OCCCN3CCCC3)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]
90
[{"value": 90.0, "product": "C(C)(=O)O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)Cl)OC)CN1CCCC1", "details": "PERCENTYIELD", "is_desired": false}]
80
CELSIUS
null
null
A solution of (2R)-7-(2-acetoxy-3-(pyrrolidin-1-yl)propoxy)-6-methoxy-3,4-dihydroquinazolin-4-one (556 mg, 1.54 mmol) in thionyl chloride (6 ml) containing DMF (3 drops) was heated at 80° C. for 4 hours. The volatiles were removed under vacuum. The residue was dissolved in methylene chloride and the organic layer was w...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1CC[NH]C1
HCl
CN(C)C=O
80
null
COc1cc2c(=O)[nH]cnc2cc1OC[C@@H](CN1CCCC1)OC(C)=O.O=S(Cl)Cl>CN(C)C=O>COc1cc2c(Cl)ncnc2cc1OC[C@@H](CN1CCCC1)OC(C)=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-15520b7aa20a499bbf62226c8aec6142
COc1cc2c(Cl)ncnc2cc1OC[C@@H](CN1CCCC1)OC(C)=O.Cc1cc2c(F)c(O)ccc2[nH]1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OC[C@@H](CN1CCCC1)OC(C)=O
C(C)(=O)O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)Cl)OC)CN1CCCC1.FC1=C2C=C(NC2=CC=C1O)C.C([O-])([O-])=O.[K+].[K+]>>C(C)(=O)O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C(=C2C=C(NC2=CC1)C)F)OC)CN1CCCC1
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:24]([O:25][CH2:26][C@@H:27]([CH2:28][N:29]3[CH2:30][CH2:31][CH2:32][CH2:33]3)[O:34][C:35]([CH3:36])=[O:37])[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])[cH:15][c:16]2[c:17]1[F:18]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9...
COc1cc2c(Cl)ncnc2cc1OC[C@@H](CN1CCCC1)OC(C)=O.Cc1cc2c(F)c(O)ccc2[nH]1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OC[C@@H](CN1CCCC1)OC(C)=O
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]
81.5
[{"value": 81.0, "product": "C(C)(=O)O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C(=C2C=C(NC2=CC1)C)F)OC)CN1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 81.5, "product": "C(C)(=O)O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C(=C2C=C(NC2=CC1)C)F)OC)CN1CCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false...
90
CELSIUS
2
HOUR
A suspension of (2R)-7-(2-acetoxy-3-(pyrrolidin-1-yl)propoxy)4-chloro-6-methoxyquinazoline (530 mg, 1.4 mmol) and 4-fluoro-5-hydroxy-2-methylindole (277 mg, 1.68 mmol), (prepared as described for the starting material in Example 237), in DMF (8 ml) containing potassium carbonate (290 mg, 2.1 mmol) was stirred at 90° C....
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
90
2
COc1cc2c(Cl)ncnc2cc1OC[C@@H](CN1CCCC1)OC(C)=O.Cc1cc2c(F)c(O)ccc2[nH]1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OC[C@@H](CN1CCCC1)OC(C)=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-62f3670c972f42379d1e7979ccdd61ac
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Nc1ccc2[nH]ccc2c1>>COc1cc2c(Nc3ccc4[nH]ccc4c3)ncnc2cc1OCCCN1CCCC1
Cl.ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1.NC=1C=C2C=CNC2=CC1>>Cl.N1C=CC2=CC(=CC=C12)NC1=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.[NH2:7][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]([NH:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][cH:13][cH:14][c:15]4[...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Nc1ccc2[nH]ccc2c1
COc1cc2c(Nc3ccc4[nH]ccc4c3)ncnc2cc1OCCCN1CCCC1
null
null
C(C)(C)O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1nc(Nc2ccc3[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].[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]
92.8
[{"value": 72.0, "product": "Cl.N1C=CC2=CC(=CC=C12)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 92.8, "product": "Cl.N1C=CC2=CC(=CC=C12)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
null
null
A solution of 4-chloro-6-methoxy-7(3-(pyrrolidin-1-yl)propoxy)quinazoline (61 mg, 0.19 mmol), (prepared as described for the starting material in Example 9), and 5-aminoindole (30 mg, 0.23 mmol) in isopropanol (2 ml) containing 6.2 N hydrogen chloride in isopropanol (33 μl) was heated at 80° C. for 6 hours. After cooli...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]C1
HCl
C(C)(C)O
80
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Nc1ccc2[nH]ccc2c1>C(C)(C)O>COc1cc2c(Nc3ccc4[nH]ccc4c3)ncnc2cc1OCCCN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-931c61833c834a56a0de166465458f50
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1ccc2cc(F)cnc2c1>>COc1cc2c(Oc3ccc4cc(F)cnc4c3)ncnc2cc1OCCCN1CCCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1.C([O-])([O-])=O.[K+].[K+].FC=1C=NC2=CC(=CC=C2C1)O>>FC=1C=NC2=CC(=CC=C2C1)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:24]([O:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:30][CH2:31][CH2:32][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[cH:12][c:13]([F: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[cH:12][c:...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1ccc2cc(F)cnc2c1
COc1cc2c(Oc3ccc4cc(F)cnc4c3)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]
44
[{"value": 44.0, "product": "FC=1C=NC2=CC(=CC=C2C1)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 43.7, "product": "FC=1C=NC2=CC(=CC=C2C1)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
2
HOUR
A mixture of 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (144 mg, 0.43 mmol), (prepared as described for the starting material in Example 67), potassium carbonate (91 mg, 0.66 mmol) and 3-fluoro-7-hydroxyquinoline (77 mg, 0.47 mmol), (prepared as described for the starting material in Example 157), in DMF (3 ...
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
2
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1ccc2cc(F)cnc2c1>CN(C)C=O>COc1cc2c(Oc3ccc4cc(F)cnc4c3)ncnc2cc1OCCCN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-11607c9d8b494044a8e8e7d5f2e20c30
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1ccc2cc(F)cnc2c1>>COc1cc2c(Oc3ccc4cc(F)cnc4c3)ncnc2cc1OCCCN1CCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1.C([O-])([O-])=O.[K+].[K+].FC=1C=NC2=CC(=CC=C2C1)O>>FC=1C=NC2=CC(=CC=C2C1)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[cH:12][c:13]([F: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[cH:12][c:13]([F:1...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1ccc2cc(F)cnc2c1
COc1cc2c(Oc3ccc4cc(F)cnc4c3)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]
28.2
[{"value": 28.0, "product": "FC=1C=NC2=CC(=CC=C2C1)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 28.2, "product": "FC=1C=NC2=CC(=CC=C2C1)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
4
HOUR
A mixture of 4-chloro-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline (218 mg, 0.68 mmol), (prepared as described for the starting material in Example 9), potassium carbonate (138 mg, 1.13 mmol) and 3-fluoro-7-hydroxyquinoline (117 mg, 0.72 mmol), (prepared as described for the starting material in Example 157), in...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncccc2c1.c1ccc2ncncc2c1.C1CC[NH]C1
HCl
CN(C)C=O
100
4
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1ccc2cc(F)cnc2c1>CN(C)C=O>COc1cc2c(Oc3ccc4cc(F)cnc4c3)ncnc2cc1OCCCN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b48f576b22e64091bd7a8f6512fa62ec
CC1=CCC(CC2CCN(C)C(=O)C2)(S(=O)(=O)[O-])C=C1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCN(C)C(=O)C1
OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC.C([O-])([O-])=O.[K+].[K+].CN1C(CC(CC1)CC1(CC=C(C=C1)C)S(=O)(=O)[O-])=O>>COC=1C=C2C(=NC=NC2=CC1OCC1CC(N(CC1)C)=O)OC=1C=C2C=C(NC2=CC1)C
CC1=CCC(S(=O)(=O)[O-])([CH2:25][CH:26]2[CH2:27][CH2:28][N:29]([CH3:30])[C:31](=[O:32])[CH2:33]2)C=C1.[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:...
CC1=CCC(CC2CCN(C)C(=O)C2)(S(=O)(=O)[O-])C=C1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCN(C)C(=O)C1
null
null
CC(=O)C.CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
f2d5edccac2080b2c6539c229872a63825a11125de9eb3381e8b7cab2bd888c2
d784cc625c03ea59ddf5ea6c0b5bb33b10fce3b4e0d8e178af93294c63ad5e22
O=C1CC(COc2ccc3c(Oc4ccc5[nH]ccc5c4)ncnc3c2)CCN1
C-C1=C-C-C(-[CH2;D2;+0:1]-[C:2](-[C:3])-[C:4]-[C:5](=[O;D1;H0:6])-[#7:7])(-S(=O)(=O)-[O-])-C=C-1.[#7;a:8]:[c:9]:[c:10]:[c:11](-[OH;D1;+0:12]):[c:13]>>[#7:7]-[C:5](=[O;D1;H0:6])-[C:4]-[C:2](-[CH2;D2;+0:1]-[O;H0;D2;+0:12]-[c:11](:[c:13]):[c:10]:[c:9]:[#7;a:8])-[C:3]
17
[{"value": 17.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CC(N(CC1)C)=O)OC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 17.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CC(N(CC1)C)=O)OC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
95
CELSIUS
4
HOUR
A mixture of 7-hydroxy-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (280 mg, 0.87 mmol), (prepared as described in Example 49), potassium carbonate (370 mg, 2.68 mmol) and 4-(1-methyl-2-oxopiperidin-4-yl)methyl-4-toluene sulphonate (260 mg, 0.87 mmol) in DMF (8 ml) was stirred at 95° C. for 4 hours and allowed to coo...
10.6084/m9.figshare.5104873.v1
null
Aromatic alcohol.Sulfonic acid
Ether
C1=CCCC=C1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HO-
CC(=O)C.CN(C)C=O
95
4
CC1=CCC(CC2CCN(C)C(=O)C2)(S(=O)(=O)[O-])C=C1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O>CC(=O)C.CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCN(C)C(=O)C1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-17c4b1ea3f47418e894ce9c36802c1b3
CN1CCNCC1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@H]1CO1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@H](O)CN1CCN(C)CC1
COC=1C=C2C(=NC=NC2=CC1OC[C@@H]1OC1)OC=1C=C2C=C(NC2=CC1)C.CN1CCNCC1>>O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)CN1CCN(CC1)C
[NH:29]1[CH2:30][CH2:31][N:32]([CH3:33])[CH2:34][CH2:35]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][C@@H: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[...
CN1CCNCC1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@H]1CO1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@H](O)CN1CCN(C)CC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Ring opening of epoxide with amine
17ab6d3921429d49d85a9af124942b034c73e1fe2f69930f0392bbbfc9046e12
97e758d6c4c8255d25541eb6c6a6f62e7dc30829ea162ca3392731efabc98a65
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCNCC3)cc2n1
[#7:1]1-[C:2]-[C:3]-[NH;D2;+0:4]-[C:5]-[C:6]-1.[#8:7]-[C:8]-[C@H;D3;+0:9]1-[CH2;D2;+0:10]-[O;H0;D2;+0:11]-1>>[#8:7]-[C:8]-[C@H;D3;+0:9](-[OH;D1;+0:11])-[CH2;D2;+0:10]-[N;H0;D3;+0:4]1-[C:3]-[C:2]-[#7:1]-[C:6]-[C:5]-1
91.2
[{"value": 91.0, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)CN1CCN(CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 91.2, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)CN1CCN(CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
70
CELSIUS
24
HOUR
A mixture of (2R)-6-methoxy-4-(2-methylindol-5-yloxy)-7-(oxiran-2-ylmethoxy)quinazoline (300 mg, 0.79 mmol), and 1-methylpiperazine (0.26 ml, 2.38 mmol) in DMF (10 ml) was stirred at 70° C. for 24 hours and allowed to cool to ambient temperature. The solvents were removed in vacuo and the residue purified by silica col...
10.6084/m9.figshare.5104873.v1
null
Ether.Secondary amine
Secondary alcohol.Tertiary amine
C1CNCC[NH]1.C1CO1
C1C[NH]CC[NH]1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1C[NH]CC[NH]1
null
CN(C)C=O
70
24
CN1CCNCC1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@H]1CO1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@H](O)CN1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-5dc63d9ad4014b659f77e59b495d353f
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)OC[C@H]2CO2)cc1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@H]1CO1
OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC.C([O-])([O-])=O.[K+].[K+].CC1=CC=C(C=C1)S(=O)(=O)OC[C@H]2CO2>>COC=1C=C2C(=NC=NC2=CC1OC[C@@H]1OC1)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][C@H:26]2[CH2:27][O:28]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...
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)OC[C@H]2CO2)cc1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@H]1CO1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
b5213736859cf91483a02f350869986d9b7674724716adef8a5d7a4bbdb79574
3d107e624e135e10014c7bf413dd0be27e1e4488f039e545b94cb1680b764158
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OC[C@H]3CO3)cc2n1
C-c1:c:c:c(-S(=O)(=O)-O-[CH2;D2;+0:1]-[C:2]2-[#8:3]-[C:4]-2):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]1-[#8:3]-[C:4]-1):[c:10]
53
[{"value": 53.0, "product": "COC=1C=C2C(=NC=NC2=CC1OC[C@@H]1OC1)OC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 52.7, "product": "COC=1C=C2C(=NC=NC2=CC1OC[C@@H]1OC1)OC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
2
HOUR
A mixture of 7-hydroxy-6-methoxy-4-(2-methylindol-5-yloxy)quinazoline (300 mg, 0.93 mmol), (prepared as described in Example 49), potassium carbonate (385 mg, 2.79 mmol) and (2R)-(−)-glycidyl tosylate (426 mg, 2.79 mmol) in DMF (15 ml) was stirred at 60° C. for 2 hours and allowed to cool to ambient temperature. The re...
10.6084/m9.figshare.5104873.v1
null
Tosylate.Aromatic alcohol
Ether
c1ccccc1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CO1
TsOH.HO-
CN(C)C=O
60
2
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)OC[C@H]2CO2)cc1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@H]1CO1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-ecdf3e68612844bfb6627c1e01714b97
CCNCC.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@H]1CO1>>CCN(CC)C[C@@H](O)COc1cc2ncnc(Oc3ccc4[nH]c(C)cc4c3)c2cc1OC
COC=1C=C2C(=NC=NC2=CC1OC[C@@H]1OC1)OC=1C=C2C=C(NC2=CC1)C.C(C)NCC>>C(C)N(CC)C[C@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)O
[CH3:1][CH2:2][NH:3][CH2:4][CH3:5].[CH2:6]1[C@H:7]([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])[O:8]1>>[CH3:1][CH2:2][N:3]([CH2:4][CH3:5])[CH2:6][C@@H:7]([OH:8])[CH2:9][O:10][c:11]1[cH:12]...
CCNCC.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@H]1CO1
CCN(CC)C[C@@H](O)COc1cc2ncnc(Oc3ccc4[nH]c(C)cc4c3)c2cc1OC
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Ring opening of epoxide with amine
8b0e6adfb78f36f9ea38287644fe13d1ed2aa3ea65e10cc66a65b05c37e2e473
97e758d6c4c8255d25541eb6c6a6f62e7dc30829ea162ca3392731efabc98a65
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
[#8:1]-[C:2]-[C@H;D3;+0:3]1-[CH2;D2;+0:4]-[O;H0;D2;+0:5]-1.[C;D1;H3:6]-[C:7]-[NH;D2;+0:8]-[C:9]-[C;D1;H3:10]>>[#8:1]-[C:2]-[C@H;D3;+0:3](-[OH;D1;+0:5])-[CH2;D2;+0:4]-[N;H0;D3;+0:8](-[C:7]-[C;D1;H3:6])-[C:9]-[C;D1;H3:10]
81
[{"value": 81.0, "product": "C(C)N(CC)C[C@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 80.9, "product": "C(C)N(CC)C[C@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
70
CELSIUS
24
HOUR
A mixture of (2R)-6-methoxy-4-(2-methylindol-5-yloxy)-7-(oxiran-2-ylmethoxy)quinazoline (300 mg, 0.79 mmol), (prepared as described for the starting material in Example 269), and diethylamine (0.25 ml, 2.38 mmol) in DMF (10 ml) was stirred at 70° C. for 24 hours and allowed to cool to ambient temperature. The solvents ...
10.6084/m9.figshare.5104873.v1
null
Ether.Secondary amine
Secondary alcohol.Tertiary amine
C1CO1
null
c1ccc2ncncc2c1.c1ccc2[nH]ccc2c1
null
CN(C)C=O
70
24
CCNCC.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@H]1CO1>CN(C)C=O>CCN(CC)C[C@@H](O)COc1cc2ncnc(Oc3ccc4[nH]c(C)cc4c3)c2cc1OC
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-54e6fc74c4e14c9d92b6ddf607c1544c
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCc1ccccc1>>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1O
C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC.C(=O)[O-].[NH4+]>>OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=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][cH:13][c:14]([CH3:15])[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][cH:13][c:14]([CH3:15])[c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22]...
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCc1ccccc1
COc1cc2c(Oc3ccc4[nH]cc(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]
91
[{"value": 91.0, "product": "OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 90.4, "product": "OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
A mixture of 7-benzyloxy-6-methoxy-4-(3-methylindol-5-yloxy)quinazoline (7.76 g, 18.9 mmol), ammonium formate (17.82 g, 282 mmol) and 10% palladium on charcoal (800 mg) in DMF (350 ml) was stirred at ambient temperature for 1 hour. The catalyst was filtered off through celite and the cake washed with DMF. The solvent w...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
c1ccccc1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
Other
[Pd].CN(C)C=O
null
1
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCc1ccccc1>[Pd].CN(C)C=O>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-bac32f0e58ec4ba1a4f44945696ebe84
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cc1c[nH]c2ccc(O)cc12>>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCc1ccccc1
C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)Cl)OC.C([O-])([O-])=O.[K+].[K+].OC=1C=C2C(=CNC2=CC1)C>>C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=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][cH:13][c:14]([CH3:15])[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][cH:13][c:14]([CH3:15])[c:16...
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cc1c[nH]c2ccc(O)cc12
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCc1ccccc1
null
null
CC(=O)N(C)C
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]
73
[{"value": 73.0, "product": "C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 72.5, "product": "C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
75
CELSIUS
2
HOUR
A mixture of 7-benzyloxy-4-chloro-6-methoxyquinazoline (7.859 g, 26.1 mmol), (prepared as described for the starting material in Example 1), potassium carbonate (18.03 g, 130 mmol) and 5-hydroxy-3-methylindole (5.00 g, 34.0 mmol), (Journal of Organic Chemistry 1993, 58, 3757), in DMA (600 ml) was stirred at 75° C. for ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.c1ccccc1
HCl
CC(=O)N(C)C
75
2
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cc1c[nH]c2ccc(O)cc12>CC(=O)N(C)C>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCc1ccccc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a0787e9c37224c8d8c58490f573822c5
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1O.ClCCCN1CCOCC1>>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCCCN1CCOCC1
OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC.C([O-])([O-])=O.[K+].[K+].ClCCCN1CCOCC1>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)OC=1C=C2C(=CNC2=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][cH:13][c:14]([CH3:15])[c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[OH:24].Cl[CH2:25][CH2:26][CH2:27][N:28]1[CH2:29][CH2:30][O: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][cH:13][c:1...
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1O.ClCCCN1CCOCC1
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCCCN1CCOCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCOCC3)cc2n1
Cl-[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]
51
[{"value": 51.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)OC=1C=C2C(=CNC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 51.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)OC=1C=C2C(=CNC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
2
HOUR
A mixture of 7-hydroxy-6-methoxy-4-(3-methylindol-5-yloxy)quinazoline (800 mg, 2.49 mmol), (prepared as described in Example 271), potassium carbonate (687 mg, 4.98 mmol) and 1-chloro-3-morpholinopropane (448 mg, 2.74 mmol), (prepared as described for the starting material in Example 1), in DMF (20 ml) was stirred at 8...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1COCC[NH]1
HCl
CN(C)C=O
80
2
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1O.ClCCCN1CCOCC1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCCCN1CCOCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-f92e71d9fffa455aa45f519e5336c685
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1O.ClCCN1CCOCC1>>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCCN1CCOCC1
OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC.C([O-])([O-])=O.[K+].[K+].Cl.ClCCN1CCOCC1>>COC=1C=C2C(=NC=NC2=CC1OCCN1CCOCC1)OC=1C=C2C(=CNC2=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][cH:13][c:14]([CH3:15])[c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[OH:24].Cl[CH2:25][CH2:26][N:27]1[CH2:28][CH2:29][O: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][cH:13][c:14]([CH3:...
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1O.ClCCN1CCOCC1
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCCN1CCOCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCN3CCOCC3)cc2n1
Cl-[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]
47.1
[{"value": 47.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCN1CCOCC1)OC=1C=C2C(=CNC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 47.1, "product": "COC=1C=C2C(=NC=NC2=CC1OCCN1CCOCC1)OC=1C=C2C(=CNC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
2
HOUR
A mixture of 7-hydroxy-6-methoxy-4-(3-methylindol-5-yloxy)quinazoline (800 mg, 2.49 mmol), (prepared as described for the starting material in Example 271), potassium carbonate (1.031 g, 7.47 mmol) and 4-(2-chloroethyl)morpholine hydrochloride (510 mg, 2.74 mmol) in DMF (25 ml) was stirred at 80° C. for 2 hours and all...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1COCC[NH]1
HCl
CN(C)C=O
80
2
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1O.ClCCN1CCOCC1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCCN1CCOCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-ac332f7b11bd4d39b5c3a40f2bb40dd0
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)OCC2CCN(C(=O)OC(C)(C)C)CC2)cc1>>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCC1CCN(C(=O)OC(C)(C)C)CC1
OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC.C([O-])([O-])=O.[K+].[K+].CC1=CC=C(C=C1)S(=O)(=O)OCC1CCN(CC1)C(=O)OC(C)(C)C>>COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C(=O)OC(C)(C)C)OC=1C=C2C(=CNC2=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][cH:13][c:14]([CH3:15])[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]cc(C)c4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)OCC2CCN(C(=O)OC(C)(C)C)CC2)cc1
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)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]
63
[{"value": 63.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C(=O)OC(C)(C)C)OC=1C=C2C(=CNC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 62.7, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C(=O)OC(C)(C)C)OC=1C=C2C(=CNC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
2
HOUR
A mixture of 7-hydroxy-6-methoxy-4-(3-methylindol-5-yloxy)quinazoline (1.00 g, 3.11 mmol), (prepared as described for the starting material in Example 271), potassium carbonate (1.288 g, 9.33 mmol) and 4-(4-methylphenylsulphonyloxymethyl)-1-tert-butoxycarbonylpiperidine (1.264 g, 3.42 mmol), (prepared as described for ...
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
80
2
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)OCC2CCN(C(=O)OC(C)(C)C)CC2)cc1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCC1CCN(C(=O)OC(C)(C)C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-233237a2c74449d28a2d406ee16b0bd3
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)OOCCCN2CCS(=O)(=O)CC2)cc1>>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCCCN1CCS(=O)(=O)CC1
OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC.C([O-])([O-])=O.[K+].[K+].S(=O)(=O)(OOCCCN1CCS(CC1)(=O)=O)C1=CC=C(C)C=C1>>O=S1(CCN(CC1)CCCOC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC)=O
[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][c:14]([CH3:15])[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)OO[CH2:25][CH2:26][CH2:27][N:28]2[CH2:29][CH2:30][S:31](=[O:32])(=[O:33])[CH2:34][CH2:35]2)cc1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3...
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)OOCCCN2CCS(=O)(=O)CC2)cc1
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCCCN1CCS(=O)(=O)CC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
fedcb14b605772e360ae1ed30c4604b3d84b43339d9ff4d2021d0434b5dd15ef
c6ee87f63e41bd18f606223ec6576e0792ab2fd4ec5b723604eae1f551dc5463
O=S1(=O)CCN(CCCOc2ccc3c(Oc4ccc5[nH]ccc5c4)ncnc3c2)CC1
C-c1:c:c:c(-S(=O)(=O)-O-O-[CH2;D2;+0:1]-[C:2]-[C:3]):c:c:1.[#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]
56.5
[{"value": 56.0, "product": "O=S1(CCN(CC1)CCCOC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 56.5, "product": "O=S1(CCN(CC1)CCCOC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
75
CELSIUS
8
HOUR
A mixture of 7-hydroxy-6-methoxy-4-(3-methylindol-5-yloxy)quinazoline (600 mg, 1.87 mmol), (prepared as described for the starting material in Example 271), potassium carbonate (773 mg, 5.60 mmol) and 3-(1,1-dioxothiomorphlino)propoxy tosylate (1.296 g, 3.74 mmol) in DMF (30 ml) was stirred at 75° C. overnight and allo...
10.6084/m9.figshare.5104873.v1
null
Tosylate.Aromatic alcohol.Peroxide
Ether
c1ccccc1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CSCC[NH]1
TsOH.HO-
CN(C)C=O
75
8
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)OOCCCN2CCS(=O)(=O)CC2)cc1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCCCN1CCS(=O)(=O)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3fa7099ef0614cd4af04d9806122a0ab
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCC1CCN(C(=O)OC(C)(C)C)CC1>>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCC1CCNCC1
COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C(=O)OC(C)(C)C)OC=1C=C2C(=CNC2=CC1)C>>COC=1C=C2C(=NC=NC2=CC1OCC1CCNCC1)OC=1C=C2C(=CNC2=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][cH:13][c:14]([CH3:15])[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][cH:13][c:14...
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCC1CCN(C(=O)OC(C)(C)C)CC1
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCC1CCNCC1
null
null
FC(C(=O)O)(F)F
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]
62.2
[{"value": 62.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCNCC1)OC=1C=C2C(=CNC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 62.2, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCNCC1)OC=1C=C2C(=CNC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
A mixture of 6-methoxy-4-(3-methylindol-5-yloxy)-7-(1-tert-butoxycarbonylpiperidin-4-ylmethoxy)quinazoline (1.290 g, 2.49 mmol), (prepared as described in Example 274), in 25% trifluoroacetic acid/75% dichloromethane solution (75 ml) was stirred at ambient temperature for 2 hours. The solvents were then removed in vacu...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
C1CC[NH]CC1
C1CCNCC1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CCNCC1
HO-
FC(C(=O)O)(F)F
null
2
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCC1CCN(C(=O)OC(C)(C)C)CC1>FC(C(=O)O)(F)F>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCC1CCNCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-af9c13b920d74909b69f5bc1fb670bf3
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCC1CCNCC1.N#CCCl>>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCC1CCN(CC#N)CC1
COC=1C=C2C(=NC=NC2=CC1OCC1CCNCC1)OC=1C=C2C(=CNC2=CC1)C.C(C)N(CC)CC.ClCC#N>>C(#N)CN1CCC(CC1)COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=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][cH:13][c:14]([CH3:15])[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[CH2:27][CH2:28][NH:29][CH2:33][CH2:34]1.Cl[CH2:30][C:31]#[N: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][cH:1...
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCC1CCNCC1.N#CCCl
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCC1CCN(CC#N)CC1
null
null
CO
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
0240b8450ff2c489d02f5f0d90bc953079d7a3ab239d35a03f26392fc248b4ef
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCC3CCNCC3)cc2n1
Cl-[CH2;D2;+0:1]-[C:2]#[N;D1;H0:3].[C:4]-[C:5]-[NH;D2;+0:6]-[C:7]-[C:8]>>[C:4]-[C:5]-[N;H0;D3;+0:6](-[CH2;D2;+0:1]-[C:2]#[N;D1;H0:3])-[C:7]-[C:8]
35
[{"value": 35.0, "product": "C(#N)CN1CCC(CC1)COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC", "details": "PERCENTYIELD", "is_desired": false}]
null
null
24
HOUR
A mixture of 6-methoxy-4-(3-methylindol-5-yloxy)-7-(piperidin-4-ylmethoxy)quinazoline (460 mg, 1.10 mmol), (prepared as described in Example 276), triethylamine (5 ml) and chloroacetonitrile (0.38 ml, 6.05 mmol) in methanol (5 ml) was stirred at ambient temperature for 24 hours. The solvents were removed in vacuo and t...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1CCNCC1
C1CC[NH]CC1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
CO
null
24
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCC1CCNCC1.N#CCCl>CO>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCC1CCN(CC#N)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-c89511f52ee846f4a5080b1f6e515de3
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)OC[C@H]2CO2)cc1>>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1
OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC.C([O-])([O-])=O.[K+].[K+].CC1=CC=C(C=C1)S(=O)(=O)OC[C@H]2CO2>>COC=1C=C2C(=NC=NC2=CC1OC[C@@H]1OC1)OC=1C=C2C(=CNC2=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][cH:13][c:14]([CH3:15])[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][C@H:26]2[CH2:27][O:28]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][c:14]([CH3:15])[c:16]4...
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)OC[C@H]2CO2)cc1
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
b5213736859cf91483a02f350869986d9b7674724716adef8a5d7a4bbdb79574
3d107e624e135e10014c7bf413dd0be27e1e4488f039e545b94cb1680b764158
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OC[C@H]3CO3)cc2n1
C-c1:c:c:c(-S(=O)(=O)-O-[CH2;D2;+0:1]-[C:2]2-[#8:3]-[C:4]-2):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]1-[#8:3]-[C:4]-1):[c:10]
53.1
[{"value": 53.0, "product": "COC=1C=C2C(=NC=NC2=CC1OC[C@@H]1OC1)OC=1C=C2C(=CNC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 53.1, "product": "COC=1C=C2C(=NC=NC2=CC1OC[C@@H]1OC1)OC=1C=C2C(=CNC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
2
HOUR
A mixture of 7-hydroxy-6-methoxy-4-(3-methylindol-5-yloxy)quinazoline (1.35 g, 4.2 mmol), (prepared as described for the starting material in Example 271), potassium carbonate (1.74 g, 12.6 μmmol) and (2R)-(−)-glycidyl tosylate (1.92 g, 8.4 mmol) in DMF (25 ml) was stirred at 60° C. for 2 hours and allowed to cool to a...
10.6084/m9.figshare.5104873.v1
null
Tosylate.Aromatic alcohol
Ether
c1ccccc1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CO1
TsOH.HO-
CN(C)C=O
60
2
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)OC[C@H]2CO2)cc1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3ba7a97d699e4b688bca43eee5c7f5b7
C1CCNC1.COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1>>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H](O)CN1CCCC1
COC=1C=C2C(=NC=NC2=CC1OC[C@@H]1OC1)OC=1C=C2C(=CNC2=CC1)C.N1CCCC1>>O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=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][cH:13][c:14]([CH3:15])[c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[O:24][CH2:25][C@@H: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][cH:13][c:...
C1CCNC1.COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H](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
[#8:1]-[C:2]-[C@H;D3;+0:3]1-[CH2;D2;+0:4]-[O;H0;D2;+0:5]-1.[C:6]1-[C:7]-[C:8]-[C:9]-[NH;D2;+0:10]-1>>[#8:1]-[C:2]-[C@H;D3;+0:3](-[OH;D1;+0:5])-[CH2;D2;+0:4]-[N;H0;D3;+0:10]1-[C:6]-[C:7]-[C:8]-[C:9]-1
88.2
[{"value": 88.0, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC)CN1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 88.2, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC)CN1CCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
24
HOUR
A mixture of (2R)-6-methoxy-4-(3-methylindol-5-yloxy)-7-(oxiran-2-ylmethoxy)quinazoline (300 mg, 0.65 mmol), (prepared as described in Example 278), and pyrrolidine (0.17 ml, 2.04 mmol) in DMF (5 ml) was stirred at 60° C. for 24 hours and allowed to cool to ambient temperature. The solvents were removed in vacuo and th...
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
60
24
C1CCNC1.COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H](O)CN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-2069c05e6da748919de375efa853f1c2
CN1CCNCC1.COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1>>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H](O)CN1CCN(C)CC1
COC=1C=C2C(=NC=NC2=CC1OC[C@@H]1OC1)OC=1C=C2C(=CNC2=CC1)C.CN1CCNCC1.CN(C)C=O>>O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC)CN1CCN(CC1)C
[NH:29]1[CH2:30][CH2:31][N:32]([CH3:33])[CH2:34][CH2:35]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][c:14]([CH3:15])[c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[O:24][CH2:25][C@@H: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[...
CN1CCNCC1.COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H](O)CN1CCN(C)CC1
null
null
null
Heteroatom Alkylation and Arylation
Ring opening of epoxide with amine
17ab6d3921429d49d85a9af124942b034c73e1fe2f69930f0392bbbfc9046e12
97e758d6c4c8255d25541eb6c6a6f62e7dc30829ea162ca3392731efabc98a65
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCNCC3)cc2n1
[#7:1]1-[C:2]-[C:3]-[NH;D2;+0:4]-[C:5]-[C:6]-1.[#8:7]-[C:8]-[C@H;D3;+0:9]1-[CH2;D2;+0:10]-[O;H0;D2;+0:11]-1>>[#8:7]-[C:8]-[C@H;D3;+0:9](-[OH;D1;+0:11])-[CH2;D2;+0:10]-[N;H0;D3;+0:4]1-[C:3]-[C:2]-[#7:1]-[C:6]-[C:5]-1
80
[{"value": 80.0, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC)CN1CCN(CC1)C", "details": "PERCENTYIELD", "is_desired": false}]
60
CELSIUS
24
HOUR
A mixture of (2R)-6-methoxy-4-(3-methylindol-5-yloxy)-7-(oxiran-2-ylmethoxy)quinazoline (350 mg, 0.93 mmol), (prepared as described in Example 278), and 1-methylpiperazine (0.31 ml, 2.78 mmol) in DMF (5 ml) was stirred at 60° C. for 24 hours and allowed to cool to ambient temperature. The solvents were removed in vacuo...
10.6084/m9.figshare.5104873.v1
null
Ether.Secondary amine
Secondary alcohol.Tertiary amine
C1CNCC[NH]1.C1CO1
C1C[NH]CC[NH]1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1C[NH]CC[NH]1
null
null
60
24
CN1CCNCC1.COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1>>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H](O)CN1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-128583cbc4174050a3b7291e19927c4c
CNC.COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1>>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H](O)CN(C)C
COC=1C=C2C(=NC=NC2=CC1OC[C@@H]1OC1)OC=1C=C2C(=CNC2=CC1)C.CNC.C(C)O>>O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC)CN(C)C
[NH:29]([CH3:30])[CH3:31].[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]4[nH:12][cH:13][c:14]([CH3:15])[c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[O:24][CH2:25][C@@H: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][cH:13][c:14]([CH3:15])[c:...
CNC.COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H](O)CN(C)C
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Ring opening of epoxide with amine
8b0e6adfb78f36f9ea38287644fe13d1ed2aa3ea65e10cc66a65b05c37e2e473
97e758d6c4c8255d25541eb6c6a6f62e7dc30829ea162ca3392731efabc98a65
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
[#8:1]-[C:2]-[C@H;D3;+0:3]1-[CH2;D2;+0:4]-[O;H0;D2;+0:5]-1.[C;D1;H3:6]-[NH;D2;+0:7]-[C;D1;H3:8]>>[#8:1]-[C:2]-[C@H;D3;+0:3](-[OH;D1;+0:5])-[CH2;D2;+0:4]-[N;H0;D3;+0:7](-[C;D1;H3:6])-[C;D1;H3:8]
78
[{"value": 78.0, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC)CN(C)C", "details": "PERCENTYIELD", "is_desired": false}]
60
CELSIUS
24
HOUR
A mixture of (2R)-6-methoxy-4-(3-methylindol-5-yloxy)-7-(oxiran-2-ylmethoxy)quinazoline (350 mg, 0.93 mmol), (prepared as described in Example 278), and 2.0 M dimethylamine in ethanol (4.60 ml, 9.30 mmol) in DMF (5 ml) was stirred at 60° C. for 24 hours and allowed to cool to ambient temperature. The solvents were remo...
10.6084/m9.figshare.5104873.v1
null
Ether.Secondary amine
Secondary alcohol.Tertiary amine
C1CO1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
null
CN(C)C=O
60
24
CNC.COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H](O)CN(C)C
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e045e7ee22184581a00b2f26425cec95
CC(C)N.COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1>>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H](O)CNC(C)C
COC=1C=C2C(=NC=NC2=CC1OC[C@@H]1OC1)OC=1C=C2C(=CNC2=CC1)C.C(C)(C)N>>O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC)CNC(C)C
[NH2:29][CH:30]([CH3:31])[CH3:32].[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][cH:13][c:14]([CH3:15])[c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[O:24][CH2:25][C@@H: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][cH:13][c:14]([CH3...
CC(C)N.COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H](O)CNC(C)C
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
f75f8fec78b0ee9c8e880101c8c57c2a3edaac070bc7ad0163a34826e2af8c65
04c78336d85647f6dca3040f384f77009d1b541aac7f8ccf33aa9798091ceab8
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
[#8:1]-[C:2]-[C@H;D3;+0:3]1-[CH2;D2;+0:4]-[O;H0;D2;+0:5]-1.[C;D1;H3:6]-[C:7](-[C;D1;H3:8])-[NH2;D1;+0:9]>>[#8:1]-[C:2]-[C@H;D3;+0:3](-[OH;D1;+0:5])-[CH2;D2;+0:4]-[NH;D2;+0:9]-[C:7](-[C;D1;H3:6])-[C;D1;H3:8]
75.6
[{"value": 75.0, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC)CNC(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 75.6, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC)CNC(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
24
HOUR
A mixture of (2R)-6-methoxy-4-(3-methylindol-5-yloxy)-7-(oxiran-2-ylmethoxy)quinazoline (350 mg, 0.93 mmol), (prepared as described in Example 278), and isopropylamine (0.29 ml, 4.65 mmol) in DMF (5 ml) was stirred at 100° C. for 24 hours and allowed to cool to ambient temperature. The solvents were removed in vacuo an...
10.6084/m9.figshare.5104873.v1
null
Ether.Primary amine
Secondary alcohol.Secondary amine
C1CO1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
null
CN(C)C=O
100
24
CC(C)N.COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H](O)CNC(C)C
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e7731da2f7f243159009b2381ecd2a75
CC(C)NC(C)C.COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1>>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H](O)CN(C(C)C)C(C)C
COC=1C=C2C(=NC=NC2=CC1OC[C@@H]1OC1)OC=1C=C2C(=CNC2=CC1)C.C(C)(C)NC(C)C>>O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC)CN(C(C)C)C(C)C
[NH:29]([CH:30]([CH3:31])[CH3:32])[CH:33]([CH3:34])[CH3:35].[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][c:14]([CH3:15])[c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[O:24][CH2:25][C@@H: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]...
CC(C)NC(C)C.COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H](O)CN(C(C)C)C(C)C
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Ring opening of epoxide with amine
8b0e6adfb78f36f9ea38287644fe13d1ed2aa3ea65e10cc66a65b05c37e2e473
97e758d6c4c8255d25541eb6c6a6f62e7dc30829ea162ca3392731efabc98a65
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
[#8:1]-[C:2]-[C@H;D3;+0:3]1-[CH2;D2;+0:4]-[O;H0;D2;+0:5]-1.[C;D1;H3:6]-[C:7](-[C;D1;H3:8])-[NH;D2;+0:9]-[C:10](-[C;D1;H3:11])-[C;D1;H3:12]>>[#8:1]-[C:2]-[C@H;D3;+0:3](-[OH;D1;+0:5])-[CH2;D2;+0:4]-[N;H0;D3;+0:9](-[C:7](-[C;D1;H3:6])-[C;D1;H3:8])-[C:10](-[C;D1;H3:11])-[C;D1;H3:12]
93
[{"value": 93.0, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC)CN(C(C)C)C(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 89.4, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC)CN(C(C)C)C(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
130
CELSIUS
24
HOUR
A mixture of (2R)-6-methoxy-4-(3-methylindol-5-yloxy)-7-(oxiran-2-ylmethoxy)quinazoline (350 mg, 0.93 mmol), (prepared as described in Example 278), and diisopropylamine (0.78 ml, 5.58 mmol) in DMF (10 ml) was stirred at 130° C. for 24 hours and allowed to cool to ambient temperature. The solvents were removed in vacuo...
10.6084/m9.figshare.5104873.v1
null
Ether.Secondary amine
Secondary alcohol.Tertiary amine
C1CO1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
null
CN(C)C=O
130
24
CC(C)NC(C)C.COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H](O)CN(C(C)C)C(C)C
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-104228acecfb43e6a0a22670d44d151d
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1.NCCCN1CCOCC1>>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H](O)CNCCCN1CCOCC1
COC=1C=C2C(=NC=NC2=CC1OC[C@@H]1OC1)OC=1C=C2C(=CNC2=CC1)C.NCCCN1CCOCC1>>O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC)CNCCCN1CCOCC1
[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][c:14]([CH3:15])[c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[O:24][CH2:25][C@@H:26]1[O:27][CH2:28]1.[NH2:29][CH2:30][CH2:31][CH2:32][N:33]1[CH2:34][CH2:35][O:36][CH2:37][CH2:38]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3...
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1.NCCCN1CCOCC1
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H](O)CNCCCN1CCOCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
f75f8fec78b0ee9c8e880101c8c57c2a3edaac070bc7ad0163a34826e2af8c65
04c78336d85647f6dca3040f384f77009d1b541aac7f8ccf33aa9798091ceab8
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCNCCCN3CCOCC3)cc2n1
[#8:1]-[C:2]-[C@H;D3;+0:3]1-[CH2;D2;+0:4]-[O;H0;D2;+0:5]-1.[C:6]-[C:7]-[NH2;D1;+0:8]>>[#8:1]-[C:2]-[C@H;D3;+0:3](-[OH;D1;+0:5])-[CH2;D2;+0:4]-[NH;D2;+0:8]-[C:7]-[C:6]
46
[{"value": 46.0, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC)CNCCCN1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 45.9, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC)CNCCCN1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
70
CELSIUS
null
null
A mixture of (2R)-6-methoxy-4-(3-methylindol-5-yloxy)-7-(oxiran-2-ylmethoxy)quinazoline (100 mg, 0.28 mmol), (prepared as described in Example 278), and 4-(3-aminopropyl)morpholine (0.12 ml, 0.84 mmol) in DMF (5 ml) was heated to 70° C. for 3 hours. The solvents were removed in vacuo and the residue taken up in dichlor...
10.6084/m9.figshare.5104873.v1
null
Ether.Primary amine
Secondary alcohol.Secondary amine
C1CO1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1COCC[NH]1
null
CN(C)C=O
70
null
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1.NCCCN1CCOCC1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H](O)CNCCCN1CCOCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-4ad3967b21f84f3588d6a0ac8d52ec97
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1>>COc1ccc2ncnc(Oc3ccc4[nH]cc(C)c4c3)c2c1
COC=1C=C2C(=NC=NC2=CC1OC[C@@H]1OC1)OC=1C=C2C(=CNC2=CC1)C.NCCCN1CCN(CC1)C>>COC=1C=C2C(=NC=NC2=CC1)OC=1C=C2C(=CNC2=CC1)C
C1O[C@H]1CO[c:4]1[c:3]([O:2][CH3:1])[cH:23][c:22]2[c:6]([cH:5]1)[n:7][cH:8][n:9][c:10]2[O:11][c:12]1[cH:13][cH:14][c:15]2[nH:16][cH:17][c:18]([CH3:19])[c:20]2[cH:21]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[n:7][cH:8][n:9][c:10]([O:11][c:12]3[cH:13][cH:14][c:15]4[nH:16][cH:17][c:18]([CH3:19])[c:20]4[cH:21]3)[c:22]2[cH:23...
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1
COc1ccc2ncnc(Oc3ccc4[nH]cc(C)c4c3)c2c1
null
null
CN(C)C=O
Reduction
OtherReaction
a7bf2d7147ce1e3758997759ed14aac4b01a32af045af979a1c7bac98056e4bd
1556a72485df4201aca96fb7a0c321edf07cb063300030d429a36e916471ff2c
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
[#8:1]-[c:2]1:[c:3]:[c:4]2:[c:5]:[#7;a:6]:[c:7]:[#7;a:8]:[c:9]:2:[c:10]:[c;H0;D3;+0:11]:1-O-C-[C@@H]1-C-O-1>>[#8:1]-[c:2]1:[c:3]:[c:4]2:[c:5]:[#7;a:6]:[c:7]:[#7;a:8]:[c:9]:2:[c:10]:[cH;D2;+0:11]:1
51.5
[{"value": 31.0, "product": "COC=1C=C2C(=NC=NC2=CC1)OC=1C=C2C(=CNC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 51.5, "product": "COC=1C=C2C(=NC=NC2=CC1)OC=1C=C2C(=CNC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
70
CELSIUS
null
null
A mixture of (2R)-6-methoxy-4-(3-methylindol-5-yloxy)-7-(oxiran-2-ylmethoxy)quinazoline (100 mg, 0.28 mmol), (prepared as described in Example 278), and 1-(3-aminopropyl)-4-methylpiperazine (132 mg, 0.84 mmol) in DMF (5 ml) was heated to 70° C. for 3 hours. The solvents were removed in vacuo and the residue taken up in...
10.6084/m9.figshare.5104873.v1
null
Ether.Ether
null
C1CO1.c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.c1ccc2[nH]ccc2c1
HO-
CN(C)C=O
70
null
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1>CN(C)C=O>COc1ccc2ncnc(Oc3ccc4[nH]cc(C)c4c3)c2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-1bee15e9315e496b8ca9c0c95b460a1c
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1.NCCCN1CCCC1>>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H](O)CNCCCN1CCCC1
COC=1C=C2C(=NC=NC2=CC1OC[C@@H]1OC1)OC=1C=C2C(=CNC2=CC1)C.NCCCN1CCCC1>>O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC)CNCCCN1CCCC1
[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][c:14]([CH3:15])[c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[O:24][CH2:25][C@@H:26]1[O:27][CH2:28]1.[NH2:29][CH2:30][CH2:31][CH2:32][N:33]1[CH2:34][CH2:35][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]...
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1.NCCCN1CCCC1
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H](O)CNCCCN1CCCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
f75f8fec78b0ee9c8e880101c8c57c2a3edaac070bc7ad0163a34826e2af8c65
04c78336d85647f6dca3040f384f77009d1b541aac7f8ccf33aa9798091ceab8
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCNCCCN3CCCC3)cc2n1
[#8:1]-[C:2]-[C@H;D3;+0:3]1-[CH2;D2;+0:4]-[O;H0;D2;+0:5]-1.[C:6]-[C:7]-[NH2;D1;+0:8]>>[#8:1]-[C:2]-[C@H;D3;+0:3](-[OH;D1;+0:5])-[CH2;D2;+0:4]-[NH;D2;+0:8]-[C:7]-[C:6]
68
[{"value": 68.0, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC)CNCCCN1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 66.6, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=CNC2=CC1)C)OC)CNCCCN1CCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
null
null
A mixture of (2R)-6-methoxy-4-(3-methylindol-5-yloxy)-7-(oxiran-2-ylmethoxy)quinazoline (70 mg, 0.19 mmol), (prepared as described in Example 278), and 1-(3-aminopropyl)pyrrolidine (74 mg, 0.58 mmol) in DMF (5 ml) was heated to 60° C. overnight. The solvents were removed in vacuo and the residue purified by column chro...
10.6084/m9.figshare.5104873.v1
null
Ether.Primary amine
Secondary alcohol.Secondary amine
C1CO1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]C1
null
CN(C)C=O
60
null
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H]1CO1.NCCCN1CCCC1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OC[C@H](O)CNCCCN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-156bc0493faf4ea6b372c226721e4d54
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1ccc2[nH]ccc2c1Br>>COc1cc2c(Oc3ccc4[nH]ccc4c3Br)ncnc2cc1OCCCN1CCCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1.C([O-])([O-])=O.[K+].[K+].BrC1=C2C=CNC2=CC=C1O>>BrC1=C2C=CNC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1
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][cH:13][cH:14][c:15]2[c:16]1[Br:17]>>[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...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1ccc2[nH]ccc2c1Br
COc1cc2c(Oc3ccc4[nH]ccc4c3Br)ncnc2cc1OCCCN1CCCCC1
null
null
CC(=O)N(C)C
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]
44.3
[{"value": 44.0, "product": "BrC1=C2C=CNC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 44.3, "product": "BrC1=C2C=CNC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
90
CELSIUS
3
HOUR
A mixture of 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (380 mg, 1.13 mmol), (prepared as described for the starting material in Example 67), potassium carbonate (469 mg, 3.4 mmol), 4-bromo-5-hydroxyindole (240 mg, 1.13 mmol) and DMA (4.0 ml) were stirred at 90° C. for 3 hours and allowed to cool to ambient ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
CC(=O)N(C)C
90
3
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1ccc2[nH]ccc2c1Br>CC(=O)N(C)C>COc1cc2c(Oc3ccc4[nH]ccc4c3Br)ncnc2cc1OCCCN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b0cff2d5040b4c34a8d7dbfcf7338615
CCO.CCOC(=O)c1cc2c(Br)c(O)ccc2[nH]1>>COc1ccc2[nH]c(C(=O)O)cc2c1Br
BrC1=C2C=C(NC2=CC=C1O)C(=O)OCC.C(C)O.[OH-].[K+]>>BrC1=C2C=C(NC2=CC=C1OC)C(=O)O
OC[CH3:1].CC[O:11][C:9]([c:8]1[nH:7][c:6]2[cH:5][cH:4][c:3]([OH:2])[c:14]([Br:15])[c:13]2[cH:12]1)=[O:10]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[nH:7][c:8]([C:9](=[O:10])[OH:11])[cH:12][c:13]2[c:14]1[Br:15]
CCO.CCOC(=O)c1cc2c(Br)c(O)ccc2[nH]1
COc1ccc2[nH]c(C(=O)O)cc2c1Br
null
null
O
Heteroatom Alkylation and Arylation
OtherReaction
0db00e48ffe5800295c995015791d2855681eceda8c116b62320b3c2b225d830
9653d63179b641796999681486e0249947865421087fe94dd6954f3668089e9b
c1ccc2[nH]ccc2c1
C-C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]:[#7;a:5].[OH;D1;+0:6]-[c:7](:[c:8]):[c:9].O-C-[CH3;D1;+0:10]>>[#7;a:5]:[c:4]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1].[CH3;D1;+0:10]-[O;H0;D2;+0:6]-[c:7](:[c:8]):[c:9]
96
[{"value": 96.0, "product": "BrC1=C2C=C(NC2=CC=C1OC)C(=O)O", "details": "PERCENTYIELD", "is_desired": false}]
50
CELSIUS
1
HOUR
Ethyl 4-bromo-5-hydroxyindole-2-carboxylate (1.49 g, 5 mmol.), (Jnl. Org. Chem. 1984, 49, 4761), was dissolved in ethanol (10 ml) and water (3.5 ml). Potassium hydroxide (840 mg) was added and the mixture stirred at 50° C. under an atmosphere of nitrogen for 1 hour then cooled to ambient temperature. The solvent was ev...
10.6084/m9.figshare.5104873.v1
null
Ester.Primary alcohol.Aromatic alcohol
Carboxylic acid.Ether
null
null
c1ccc2[nH]ccc2c1
HO-
O
50
1
CCO.CCOC(=O)c1cc2c(Br)c(O)ccc2[nH]1>O>COc1ccc2[nH]c(C(=O)O)cc2c1Br
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d6f2ecd05d344eecbf92022007dacf5d
COc1ccc2[nH]c(C(=O)O)cc2c1Br>>COc1ccc2[nH]ccc2c1Br
BrC1=C2C=C(NC2=CC=C1OC)C(=O)O.N1=CC=CC2=CC=CC=C12>>BrC1=C2C=CNC2=CC=C1OC
O=C(O)[c:8]1[nH:7][c:6]2[cH:5][cH:4][c:3]([O:2][CH3:1])[c:11]([Br:12])[c:10]2[cH:9]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[nH:7][cH:8][cH:9][c:10]2[c:11]1[Br:12]
COc1ccc2[nH]c(C(=O)O)cc2c1Br
COc1ccc2[nH]ccc2c1Br
null
[Cr](=O)([O-])[O-].[Cu+2]
null
Reduction
Decarboxylation
d5c4709a8d4e49fe37f49e81e5c384f60c93fbbbbfa4eb758c4725d90cd07b32
292164ffdf89eeb341ee9424f24084b252a703a26bb77721b558b0f8a8528c45
c1ccc2[nH]ccc2c1
O-C(=O)-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[c:4]:[c:5]:1>>[#7;a:2]1:[c:3]:[c:4]:[c:5]:[cH;D2;+0:1]:1
67
[{"value": 60.0, "product": "BrC1=C2C=CNC2=CC=C1OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 67.0, "product": "BrC1=C2C=CNC2=CC=C1OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
245
CELSIUS
null
null
4-Bromo-5-methoxyindole-2-carboxylic acid (1.25 g, 4.19 mmol), quinoline (15 ml) and copper chromite (313 mg) were mixed together. Nitrogen was gently bubbled through the mixture for 5 minutes, then the mixture heated quickly to 245° C. under an atmosphere of nitrogen. After 90 minutes the mixture was cooled to ambient...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid
null
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1
Other
[Cr](=O)([O-])[O-].[Cu+2]
245
null
COc1ccc2[nH]c(C(=O)O)cc2c1Br>[Cr](=O)([O-])[O-].[Cu+2]>COc1ccc2[nH]ccc2c1Br
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-0fb4521827e14255ad8beb0e5762aff1
COc1ccc2[nH]ccc2c1Br>>Oc1ccc2[nH]ccc2c1Br
B(Br)(Br)Br.BrC1=C2C=CNC2=CC=C1OC>>BrC1=C2C=CNC2=CC=C1O
C[O:1][c:2]1[cH:3][cH:4][c:5]2[nH:6][cH:7][cH:8][c:9]2[c:10]1[Br:11]>>[OH:1][c:2]1[cH:3][cH:4][c:5]2[nH:6][cH:7][cH:8][c:9]2[c:10]1[Br:11]
COc1ccc2[nH]ccc2c1Br
Oc1ccc2[nH]ccc2c1Br
null
null
ClCCl
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]
58
[{"value": 55.0, "product": "BrC1=C2C=CNC2=CC=C1O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 58.0, "product": "BrC1=C2C=CNC2=CC=C1O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
A solution of 4-bromo-5-methoxyindole (540 mg, 2.4 mmol) in dichloromethane (12 ml) was cooled to −40° C. under an atmosphere of nitrogen. Boron tribromide (4.8 ml of a 1M solution in dichloromethane, 4.8 mmol) was added dropwise then the mixture warmed to ambient temperature and stirred for 1 hour. The mixture was dil...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1ccc2[nH]ccc2c1
Other
ClCCl
null
1
COc1ccc2[nH]ccc2c1Br>ClCCl>Oc1ccc2[nH]ccc2c1Br
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-2653284ecc644473ae51d390ec995ab4
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Cn1ccc2cc(O)ccc21>>COc1cc2c(Oc3ccc4c(ccn4C)c3)ncnc2cc1OCCCN1CCCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1.C([O-])([O-])=O.[K+].[K+].OC=1C=C2C=CN(C2=CC1)C>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCCC1)OC=1C=C2C=CN(C2=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[c:12]([cH:13][cH:14][n:15]2[CH3:16])[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[c:12]([cH:13]...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Cn1ccc2cc(O)ccc21
COc1cc2c(Oc3ccc4c(ccn4C)c3)ncnc2cc1OCCCN1CCCCC1
null
null
CC(=O)N(C)C
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]
49
[{"value": 49.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCCC1)OC=1C=C2C=CN(C2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 48.7, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCCC1)OC=1C=C2C=CN(C2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
90
CELSIUS
4
HOUR
Nitrogen was bubbled through a mixture of 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (335 mg, 0.68 mmol), (prepared as described for the starting material in Example 67), potassium carbonate (281.5 mg, 2.04 mmol), 5-hydroxy-1methylindole (100 mg, 0.68 mmol) and DMA (4.0 ml) for 5 minutes. The mixture was the...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
CC(=O)N(C)C
90
4
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Cn1ccc2cc(O)ccc21>CC(=O)N(C)C>COc1cc2c(Oc3ccc4c(ccn4C)c3)ncnc2cc1OCCCN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-8ab4d48fa8a74ecd8be1088086b8319b
Cn1ccc2cc(OCc3ccccc3)ccc21>>Cn1ccc2cc(O)ccc21
C(C1=CC=CC=C1)OC=1C=C2C=CN(C2=CC1)C.[H][H]>>OC=1C=C2C=CN(C2=CC1)C
c1ccc(C[O:8][c:7]2[cH:6][c:5]3[cH:4][cH:3][n:2]([CH3:1])[c:11]3[cH:10][cH:9]2)cc1>>[CH3:1][n:2]1[cH:3][cH:4][c:5]2[cH:6][c:7]([OH:8])[cH:9][cH:10][c:11]12
Cn1ccc2cc(OCc3ccccc3)ccc21
Cn1ccc2cc(O)ccc21
null
[Pd]
C(C)O
Deprotection
Hydroxyl benzyl deprotection
36869d1fe85185a14d9eb30bf05178c600a9b6eca277ffaf3803578c30e0bf5d
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2[nH]ccc2c1
[c:1]:[c:2](-[O;H0;D2;+0:3]-C-c1:c:c:c:c:c:1):[c:4]>>[OH;D1;+0:3]-[c:2](:[c:1]):[c:4]
97
[{"value": 97.0, "product": "OC=1C=C2C=CN(C2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 90.9, "product": "OC=1C=C2C=CN(C2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 5-benzyloxy-1-methylindole (3.5 g, 15.7 mmol), in ethanol (100 ml) was hydrogenated at ambient temperature and 1 atmosphere pressure hydrogen for 4 hours using 10% palladium on carbon (0.5 g) as catalyst. The catalyst was filtered off and the filtrate evaporated in vacuo. The residue was purified by silic...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
c1ccccc1
null
c1ccc2[nH]ccc2c1
Other
[Pd].C(C)O
null
null
Cn1ccc2cc(OCc3ccccc3)ccc21>[Pd].C(C)O>Cn1ccc2cc(O)ccc21
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e3241eccbfb14974b801d4e0361b08ed
C1CCNC1.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CO1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H](O)CN1CCCC1
N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OC[C@@H]1OC1.N1CCCC1>>O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN1CCCC1
[NH: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][cH:13][cH:14][c:15]4[cH:16]3)[n:17][cH:18][n:19][c:20]2[cH:21][c:22]1[O:23][CH2:24][C@@H:25]1[O:26][CH2:27]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...
C1CCNC1.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CO1
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H](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
[#8:1]-[C:2]-[C@H;D3;+0:3]1-[CH2;D2;+0:4]-[O;H0;D2;+0:5]-1.[C:6]1-[C:7]-[C:8]-[C:9]-[NH;D2;+0:10]-1>>[#8:1]-[C:2]-[C@H;D3;+0:3](-[OH;D1;+0:5])-[CH2;D2;+0:4]-[N;H0;D3;+0:10]1-[C:6]-[C:7]-[C:8]-[C:9]-1
90.4
[{"value": 87.0, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 90.4, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN1CCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
75
CELSIUS
3
HOUR
A mixture of (2R)-4-(indol-5-yloxy)-6-methoxy-7-(oxiran-2-ylmethoxy)quinazoline (300 mg, 0.83 mmol), and pyrrolidine (176 mg, 2.48 mmol) in DMF (5 ml) was stirred at 75° C. for 3 hours under an atmosphere of nitrogen and allowed to cool to ambient temperature. The solvents were removed in vacuo and the residue purified...
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
75
3
C1CCNC1.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CO1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H](O)CN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-6fc7265f2a5a4a41999f37ea8271a87e
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)OC[C@H]2CO2)cc1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CO1
OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC.C([O-])([O-])=O.[K+].[K+].CC1=CC=C(C=C1)S(=O)(=O)OC[C@H]2CO2>>N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OC[C@@H]1OC1
[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].Cc1ccc(S(=O)(=O)O[CH2:24][C@H:25]2[CH2:26][O:27]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...
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)OC[C@H]2CO2)cc1
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CO1
null
null
CC(=O)N(C)C
Heteroatom Alkylation and Arylation
OtherReaction
b5213736859cf91483a02f350869986d9b7674724716adef8a5d7a4bbdb79574
3d107e624e135e10014c7bf413dd0be27e1e4488f039e545b94cb1680b764158
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OC[C@H]3CO3)cc2n1
C-c1:c:c:c(-S(=O)(=O)-O-[CH2;D2;+0:1]-[C:2]2-[#8:3]-[C:4]-2):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]1-[#8:3]-[C:4]-1):[c:10]
53
[{"value": 53.0, "product": "N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OC[C@@H]1OC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 52.8, "product": "N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OC[C@@H]1OC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
2
HOUR
Nitrogen was bubbled through a mixture of 7-hydroxy-4-(indol-5-yloxy)-6-methoxyquinazoline (3.07 g, 10 mmol), (prepared as described for the starting material in Example 107), potassium carbonate (4.14 g, 30 mmol) and (2R)-(−)-glycidyl tosylate (4.57 g, 20 mmol) in DMA (35 ml) for 5 minutes. The mixture was then stirre...
10.6084/m9.figshare.5104873.v1
null
Tosylate.Aromatic alcohol
Ether
c1ccccc1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CO1
TsOH.HO-
CC(=O)N(C)C
60
2
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)OC[C@H]2CO2)cc1>CC(=O)N(C)C>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CO1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a4ece89f8a164338b014d80355468b69
C1COCCN1.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CO1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H](O)CN1CCOCC1
N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OC[C@@H]1OC1.N1CCOCC1>>O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN1CCOCC1
[NH:28]1[CH2:29][CH2:30][O: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][cH:13][cH:14][c:15]4[cH:16]3)[n:17][cH:18][n:19][c:20]2[cH:21][c:22]1[O:23][CH2:24][C@@H:25]1[O:26][CH2:27]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...
C1COCCN1.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CO1
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H](O)CN1CCOCC1
null
null
null
Heteroatom Alkylation and Arylation
Ring opening of epoxide with amine
851dfc16280bb8f11cdb75741b500ca1a156bb53c804ef98fc4ef4b1d0f67de0
97e758d6c4c8255d25541eb6c6a6f62e7dc30829ea162ca3392731efabc98a65
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCOCC3)cc2n1
[#8:1]-[C:2]-[C@H;D3;+0:3]1-[CH2;D2;+0:4]-[O;H0;D2;+0:5]-1.[#8:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[#8:1]-[C:2]-[C@H;D3;+0:3](-[OH;D1;+0:5])-[CH2;D2;+0:4]-[N;H0;D3;+0:9]1-[C:8]-[C:7]-[#8:6]-[C:11]-[C:10]-1
90.4
[{"value": 85.0, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 90.4, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 292, (2R)4-(indol-5-yloxy)-6-methoxy-7-(oxiran-2-ylmethoxy)quinazoline (300 mg, 0.83 mmol), (prepared as described for the starting material in Example 292), was reacted with morpholine (211 mg, 2.49 mmol) to give (2R)-7-(2-hydroxy-3-morpholinopropoxy)-4-(indol-...
10.6084/m9.figshare.5104873.v1
null
Ether.Secondary amine
Secondary alcohol.Tertiary amine
C1COCCN1.C1CO1
C1COCC[NH]1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1COCC[NH]1
null
null
null
null
C1COCCN1.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CO1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H](O)CN1CCOCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-7e4413bdd67d4bf992102662bce3074b
C1CCNCC1.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CO1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H](O)CN1CCCCC1
N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OC[C@@H]1OC1.N1CCCCC1>>O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN1CCCCC1
[NH:28]1[CH2:29][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][cH:13][cH:14][c:15]4[cH:16]3)[n:17][cH:18][n:19][c:20]2[cH:21][c:22]1[O:23][CH2:24][C@@H:25]1[O:26][CH2:27]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:...
C1CCNCC1.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CO1
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H](O)CN1CCCCC1
null
null
null
Heteroatom Alkylation and Arylation
Ring opening of epoxide with amine
c5753b22446d1ae5dcee7a30af0c7f96061ec363349faf28c9adeaca5e033c6d
97e758d6c4c8255d25541eb6c6a6f62e7dc30829ea162ca3392731efabc98a65
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCCCC3)cc2n1
[#8:1]-[C:2]-[C@H;D3;+0:3]1-[CH2;D2;+0:4]-[O;H0;D2;+0:5]-1.[C:6]-[C:7]-[NH;D2;+0:8]-[C:9]-[C:10]>>[#8:1]-[C:2]-[C@H;D3;+0:3](-[OH;D1;+0:5])-[CH2;D2;+0:4]-[N;H0;D3;+0:8](-[C:7]-[C:6])-[C:9]-[C:10]
87.3
[{"value": 86.0, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN1CCCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 87.3, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN1CCCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 292, (2R)-4-(indol-5-yloxy)-6-methoxy-7-(oxiran-2-ylmethoxy)quinazoline (300 mg, 0.83 mmol), (prepared as described for the starting material in Example 292), was reacted with piperidine (211 mg, 2.49 mmol) to give (2R)-7-(2-hydroxy-3-piperidinopropoxy)-4-(indol...
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
null
null
null
C1CCNCC1.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CO1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H](O)CN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-ee337e3d8d924102832727e143fc3d35
CNC.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CO1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H](O)CN(C)C
N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OC[C@@H]1OC1.CNC>>O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN(C)C
[NH:28]([CH3:29])[CH3:30].[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]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[O:23][CH2:24][C@@H:25]1[O:26][CH2:27]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...
CNC.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CO1
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H](O)CN(C)C
null
null
CN(C)C=O.C1CCOC1
Heteroatom Alkylation and Arylation
Ring opening of epoxide with amine
8b0e6adfb78f36f9ea38287644fe13d1ed2aa3ea65e10cc66a65b05c37e2e473
97e758d6c4c8255d25541eb6c6a6f62e7dc30829ea162ca3392731efabc98a65
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
[#8:1]-[C:2]-[C@H;D3;+0:3]1-[CH2;D2;+0:4]-[O;H0;D2;+0:5]-1.[C;D1;H3:6]-[NH;D2;+0:7]-[C;D1;H3:8]>>[#8:1]-[C:2]-[C@H;D3;+0:3](-[OH;D1;+0:5])-[CH2;D2;+0:4]-[N;H0;D3;+0:7](-[C;D1;H3:6])-[C;D1;H3:8]
63
[{"value": 63.0, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN(C)C", "details": "PERCENTYIELD", "is_desired": false}]
75
CELSIUS
3
HOUR
A mixture of (2R)-4-(indol-5-yloxy)-6-methoxy-7-(oxiran-2-ylmethoxy)quinazoline (300 mg, 0.83 mmol), (prepared as described for the starting material in Example 292), and dimethylamine (1.24 ml of a 2M solution in THF, 2.48 mmol) in DMF (5 ml) was stirred at 75° C. for 3 hours under an atmosphere of nitrogen then allow...
10.6084/m9.figshare.5104873.v1
null
Ether.Secondary amine
Secondary alcohol.Tertiary amine
C1CO1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
null
CN(C)C=O.C1CCOC1
75
3
CNC.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CO1>CN(C)C=O.C1CCOC1>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H](O)CN(C)C
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-1db60d30b6e54133b9e84522d2a3fd09
CC(C)NC(C)C.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CO1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H](O)CN(C(C)C)C(C)C
N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OC[C@@H]1OC1.C(C)(C)NC(C)C>>O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN(C(C)C)C(C)C
[NH:28]([CH:29]([CH3:30])[CH3:31])[CH:32]([CH3:33])[CH3:34].[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[O:23][CH2:24][C@@H:25]1[O:26][CH2:27]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][...
CC(C)NC(C)C.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CO1
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H](O)CN(C(C)C)C(C)C
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Ring opening of epoxide with amine
8b0e6adfb78f36f9ea38287644fe13d1ed2aa3ea65e10cc66a65b05c37e2e473
97e758d6c4c8255d25541eb6c6a6f62e7dc30829ea162ca3392731efabc98a65
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
[#8:1]-[C:2]-[C@H;D3;+0:3]1-[CH2;D2;+0:4]-[O;H0;D2;+0:5]-1.[C;D1;H3:6]-[C:7](-[C;D1;H3:8])-[NH;D2;+0:9]-[C:10](-[C;D1;H3:11])-[C;D1;H3:12]>>[#8:1]-[C:2]-[C@H;D3;+0:3](-[OH;D1;+0:5])-[CH2;D2;+0:4]-[N;H0;D3;+0:9](-[C:7](-[C;D1;H3:6])-[C;D1;H3:8])-[C:10](-[C;D1;H3:11])-[C;D1;H3:12]
89
[{"value": 86.0, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN(C(C)C)C(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 89.0, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN(C(C)C)C(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
70
CELSIUS
19
HOUR
A mixture of (2R)-4-(indol-5-yloxy)-6-methoxy-7-(oxiran-2-ylmethoxy)quinazoline (300 mg, 0.83 mmol), (prepared as described for the starting material in Example 292), and diisopropylamine (1.35 ml, 9.7 mmol) in DMF (5 ml) was stirred at 70° C. for 19 hours under an atmosphere of nitrogen then allowed to cool to ambient...
10.6084/m9.figshare.5104873.v1
null
Ether.Secondary amine
Secondary alcohol.Tertiary amine
C1CO1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
null
CN(C)C=O
70
19
CC(C)NC(C)C.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CO1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H](O)CN(C(C)C)C(C)C
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-cc5529faea7b47769d8e6d36db5af682
C1CCNC1.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H]1CO1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H](O)CN1CCCC1
N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OC[C@H]1OC1.N1CCCC1>>O[C@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN1CCCC1
[NH: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][cH:13][cH:14][c:15]4[cH:16]3)[n:17][cH:18][n:19][c:20]2[cH:21][c:22]1[O:23][CH2:24][C@H:25]1[O:26][CH2:27]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]...
C1CCNC1.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H]1CO1
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H](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
[#8:1]-[C:2]-[C@@H;D3;+0:3]1-[CH2;D2;+0:4]-[O;H0;D2;+0:5]-1.[C:6]1-[C:7]-[C:8]-[C:9]-[NH;D2;+0:10]-1>>[#8:1]-[C:2]-[C@@H;D3;+0:3](-[OH;D1;+0:5])-[CH2;D2;+0:4]-[N;H0;D3;+0:10]1-[C:6]-[C:7]-[C:8]-[C:9]-1
93.7
[{"value": 92.0, "product": "O[C@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 93.7, "product": "O[C@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN1CCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
75
CELSIUS
3
HOUR
A mixture of (2S)-4-(indol-5-yloxy)-6-methoxy-7-(oxiran-2-ylmethoxy)quinazoline (100 mg, 0.28 mmol), and pyrrolidine (60 mg, 0.84 mmol) in DMF (5 ml) was stirred at 75° C. for 3 hours under an atmosphere of nitrogen and then allowed to cool to ambient temperature. The solvents were removed in vacuo and the residue puri...
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
75
3
C1CCNC1.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H]1CO1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H](O)CN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b0da29bb5887496a810b39b4a3b863c9
C1COCCN1.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H]1CO1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H](O)CN1CCOCC1
N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OC[C@H]1OC1.N1CCOCC1>>O[C@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN1CCOCC1
[NH:28]1[CH2:29][CH2:30][O: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][cH:13][cH:14][c:15]4[cH:16]3)[n:17][cH:18][n:19][c:20]2[cH:21][c:22]1[O:23][CH2:24][C@H:25]1[O:26][CH2:27]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]...
C1COCCN1.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H]1CO1
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H](O)CN1CCOCC1
null
null
null
Heteroatom Alkylation and Arylation
Ring opening of epoxide with amine
851dfc16280bb8f11cdb75741b500ca1a156bb53c804ef98fc4ef4b1d0f67de0
97e758d6c4c8255d25541eb6c6a6f62e7dc30829ea162ca3392731efabc98a65
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCOCC3)cc2n1
[#8:1]-[C:2]-[C@@H;D3;+0:3]1-[CH2;D2;+0:4]-[O;H0;D2;+0:5]-1.[#8:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[#8:1]-[C:2]-[C@@H;D3;+0:3](-[OH;D1;+0:5])-[CH2;D2;+0:4]-[N;H0;D3;+0:9]1-[C:8]-[C:7]-[#8:6]-[C:11]-[C:10]-1
65
[{"value": 63.0, "product": "O[C@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN1CCOCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 65.0, "product": "O[C@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN1CCOCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 297, (2S)-4-(indol-5-yloxy)-6-methoxy-7-(oxiran-2-ylmethoxy)quinazoline (100 mg, 0.28 mmol), (prepared as described for the starting material in Example 297), was reacted with morpholine (73.2 mg, 0.84 mmol) to give (2S)-7-(2-hydroxy-3-morpholinopropoxy)-4-(indo...
10.6084/m9.figshare.5104873.v1
null
Ether.Secondary amine
Secondary alcohol.Tertiary amine
C1COCCN1.C1CO1
C1COCC[NH]1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1COCC[NH]1
null
null
null
null
C1COCCN1.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H]1CO1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H](O)CN1CCOCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-21f5092f3fef41deb242548e30deb0d6
C1CCNCC1.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H]1CO1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H](O)CN1CCCCC1
N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OC[C@H]1OC1.N1CCCCC1>>O[C@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN1CCCCC1
[NH:28]1[CH2:29][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][cH:13][cH:14][c:15]4[cH:16]3)[n:17][cH:18][n:19][c:20]2[cH:21][c:22]1[O:23][CH2:24][C@H:25]1[O:26][CH2:27]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:1...
C1CCNCC1.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H]1CO1
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H](O)CN1CCCCC1
null
null
null
Heteroatom Alkylation and Arylation
Ring opening of epoxide with amine
c5753b22446d1ae5dcee7a30af0c7f96061ec363349faf28c9adeaca5e033c6d
97e758d6c4c8255d25541eb6c6a6f62e7dc30829ea162ca3392731efabc98a65
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCCCC3)cc2n1
[#8:1]-[C:2]-[C@@H;D3;+0:3]1-[CH2;D2;+0:4]-[O;H0;D2;+0:5]-1.[C:6]-[C:7]-[NH;D2;+0:8]-[C:9]-[C:10]>>[#8:1]-[C:2]-[C@@H;D3;+0:3](-[OH;D1;+0:5])-[CH2;D2;+0:4]-[N;H0;D3;+0:8](-[C:7]-[C:6])-[C:9]-[C:10]
74.1
[{"value": 73.0, "product": "O[C@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN1CCCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 74.1, "product": "O[C@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN1CCCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 297, (2S)-4-(indol-5-yloxy)-6-methoxy-7-(oxiran-2-ylmethoxy)quinazoline (100 mg, 0.28 mmol), (prepared as described for the starting material in Example 297), was reacted with piperidine (70 mg, 0.83 mmol), to give (2S)-7-(2-hydroxy-3-piperidinopropoxy)-4-(indol...
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
null
null
null
C1CCNCC1.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H]1CO1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H](O)CN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-4990c3bff8344a639ec65aae2792a863
CNC.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H]1CO1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H](O)CN(C)C
N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OC[C@H]1OC1.CNC>>O[C@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN(C)C
[NH:28]([CH3:29])[CH3:30].[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]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[O:23][CH2:24][C@H:25]1[O:26][CH2:27]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]...
CNC.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H]1CO1
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H](O)CN(C)C
null
null
CN(C)C=O.C1CCOC1
Heteroatom Alkylation and Arylation
Ring opening of epoxide with amine
8b0e6adfb78f36f9ea38287644fe13d1ed2aa3ea65e10cc66a65b05c37e2e473
97e758d6c4c8255d25541eb6c6a6f62e7dc30829ea162ca3392731efabc98a65
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
[#8:1]-[C:2]-[C@@H;D3;+0:3]1-[CH2;D2;+0:4]-[O;H0;D2;+0:5]-1.[C;D1;H3:6]-[NH;D2;+0:7]-[C;D1;H3:8]>>[#8:1]-[C:2]-[C@@H;D3;+0:3](-[OH;D1;+0:5])-[CH2;D2;+0:4]-[N;H0;D3;+0:7](-[C;D1;H3:6])-[C;D1;H3:8]
85
[{"value": 85.0, "product": "O[C@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN(C)C", "details": "PERCENTYIELD", "is_desired": false}]
75
CELSIUS
3
HOUR
A mixture of (2S)-4-(indol-5-yloxy)-6-methoxy-7-(oxiran-2-ylmethoxy)quinazoline (100 mg, 0.28 mmol), (prepared as described for the starting material in Example 297), and dimethylamine (0.42 ml of a 2M solution in THF, 0.84 mmol) in DMF (5 ml) was stirred at 75° C. for 3 hours under an atmosphere of nitrogen and then a...
10.6084/m9.figshare.5104873.v1
null
Ether.Secondary amine
Secondary alcohol.Tertiary amine
C1CO1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
null
CN(C)C=O.C1CCOC1
75
3
CNC.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H]1CO1>CN(C)C=O.C1CCOC1>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H](O)CN(C)C
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b2fd1a2e1af44c8d8c05d5b5e3710f46
CC(C)NC(C)C.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H]1CO1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H](O)CN(C(C)C)C(C)C
N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OC[C@H]1OC1.C(C)(C)NC(C)C>>O[C@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN(C(C)C)C(C)C
[NH:28]([CH:29]([CH3:30])[CH3:31])[CH:32]([CH3:33])[CH3:34].[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[O:23][CH2:24][C@H:25]1[O:26][CH2:27]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...
CC(C)NC(C)C.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H]1CO1
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H](O)CN(C(C)C)C(C)C
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Ring opening of epoxide with amine
8b0e6adfb78f36f9ea38287644fe13d1ed2aa3ea65e10cc66a65b05c37e2e473
97e758d6c4c8255d25541eb6c6a6f62e7dc30829ea162ca3392731efabc98a65
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
[#8:1]-[C:2]-[C@@H;D3;+0:3]1-[CH2;D2;+0:4]-[O;H0;D2;+0:5]-1.[C;D1;H3:6]-[C:7](-[C;D1;H3:8])-[NH;D2;+0:9]-[C:10](-[C;D1;H3:11])-[C;D1;H3:12]>>[#8:1]-[C:2]-[C@@H;D3;+0:3](-[OH;D1;+0:5])-[CH2;D2;+0:4]-[N;H0;D3;+0:9](-[C:7](-[C;D1;H3:6])-[C;D1;H3:8])-[C:10](-[C;D1;H3:11])-[C;D1;H3:12]
33.1
[{"value": 33.0, "product": "O[C@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN(C(C)C)C(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 33.1, "product": "O[C@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CN(C(C)C)C(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
70
CELSIUS
19
HOUR
A mixture of (2S)-4-(indol-5-yloxy)-6-methoxy-7-(oxiran-2-ylmethoxy)quinazoline (100 mg, 0.28 mmol), (prepared as described for the starting material in Example 297), and diisopropylamine (0.45 ml, 3.2 mmol) in DMF (5 ml) was stirred at 70° C. for 19 hours under an atmosphere of nitrogen and then allowed to cool to amb...
10.6084/m9.figshare.5104873.v1
null
Ether.Secondary amine
Secondary alcohol.Tertiary amine
C1CO1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
null
CN(C)C=O
70
19
CC(C)NC(C)C.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H]1CO1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H](O)CN(C(C)C)C(C)C
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-f68e0ecf50514aa08ad37e4da24a1fc8
CC(C)N.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CO1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H](O)CNC(C)C
N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OC[C@@H]1OC1.C(C)(C)N>>O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CNC(C)C
[NH2:28][CH:29]([CH3:30])[CH3:31].[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]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[O:23][CH2:24][C@@H:25]1[O:26][CH2:27]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...
CC(C)N.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CO1
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H](O)CNC(C)C
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
OtherReaction
f75f8fec78b0ee9c8e880101c8c57c2a3edaac070bc7ad0163a34826e2af8c65
04c78336d85647f6dca3040f384f77009d1b541aac7f8ccf33aa9798091ceab8
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
[#8:1]-[C:2]-[C@H;D3;+0:3]1-[CH2;D2;+0:4]-[O;H0;D2;+0:5]-1.[C;D1;H3:6]-[C:7](-[C;D1;H3:8])-[NH2;D1;+0:9]>>[#8:1]-[C:2]-[C@H;D3;+0:3](-[OH;D1;+0:5])-[CH2;D2;+0:4]-[NH;D2;+0:9]-[C:7](-[C;D1;H3:6])-[C;D1;H3:8]
68
[{"value": 68.0, "product": "O[C@@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CNC(C)C", "details": "PERCENTYIELD", "is_desired": false}]
75
CELSIUS
18
HOUR
A mixture of (2R)-4-(indol-5-yloxy)-6-methoxy-7-(oxiran-2-ylmethoxy)quinazoline (100 mg, 0.28 mmol), (prepared as described for the starting material in Example 292), and isopropylamine (1.0 ml) in THF (10 ml) was stirred at 75° C. for 18 hours under an atmosphere of nitrogen and then allowed to cool to ambient tempera...
10.6084/m9.figshare.5104873.v1
null
Ether.Primary amine
Secondary alcohol.Secondary amine
C1CO1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
null
C1CCOC1
75
18
CC(C)N.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CO1>C1CCOC1>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H](O)CNC(C)C
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b59b743b87ef41a7a5284757a346758f
CC(C)N.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H]1CO1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H](O)CNC(C)C
N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OC[C@H]1OC1.C(C)(C)N>>O[C@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CNC(C)C
[NH2:28][CH:29]([CH3:30])[CH3:31].[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]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[O:23][CH2:24][C@H:25]1[O:26][CH2:27]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]...
CC(C)N.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H]1CO1
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H](O)CNC(C)C
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
OtherReaction
f75f8fec78b0ee9c8e880101c8c57c2a3edaac070bc7ad0163a34826e2af8c65
04c78336d85647f6dca3040f384f77009d1b541aac7f8ccf33aa9798091ceab8
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
[#8:1]-[C:2]-[C@@H;D3;+0:3]1-[CH2;D2;+0:4]-[O;H0;D2;+0:5]-1.[C;D1;H3:6]-[C:7](-[C;D1;H3:8])-[NH2;D1;+0:9]>>[#8:1]-[C:2]-[C@@H;D3;+0:3](-[OH;D1;+0:5])-[CH2;D2;+0:4]-[NH;D2;+0:9]-[C:7](-[C;D1;H3:6])-[C;D1;H3:8]
56
[{"value": 56.0, "product": "O[C@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)CNC(C)C", "details": "PERCENTYIELD", "is_desired": false}]
75
CELSIUS
18
HOUR
A mixture of (2S)4-(indol-5-yloxy)-6-methoxy-7-(oxiran-2-ylmethoxy)quinazoline (100 mg, 0.28 mmol), (prepared as described for the starting material in Example 297), and isopropylamine (1.0 ml) in THF (10 ml) was stirred at 75° C. for 18 hours under an atmosphere of nitrogen and then allowed to cool to ambient temperat...
10.6084/m9.figshare.5104873.v1
null
Ether.Primary amine
Secondary alcohol.Secondary amine
C1CO1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
null
C1CCOC1
75
18
CC(C)N.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H]1CO1>C1CCOC1>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H](O)CNC(C)C
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-fddc19d712ef46a598684395e3faf5d2
CC(C)N.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@@H]1CO1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@@H](O)CNC(C)C
COC=1C=C2C(=NC=NC2=CC1OC[C@H]1OC1)OC=1C=C2C=C(NC2=CC1)C.C(C)(C)N>>O[C@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)CNC(C)C
[NH2:29][CH:30]([CH3:31])[CH3:32].[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: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][C@H: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]([CH3:14])[cH...
CC(C)N.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@@H]1CO1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@@H](O)CNC(C)C
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
OtherReaction
f75f8fec78b0ee9c8e880101c8c57c2a3edaac070bc7ad0163a34826e2af8c65
04c78336d85647f6dca3040f384f77009d1b541aac7f8ccf33aa9798091ceab8
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
[#8:1]-[C:2]-[C@@H;D3;+0:3]1-[CH2;D2;+0:4]-[O;H0;D2;+0:5]-1.[C;D1;H3:6]-[C:7](-[C;D1;H3:8])-[NH2;D1;+0:9]>>[#8:1]-[C:2]-[C@@H;D3;+0:3](-[OH;D1;+0:5])-[CH2;D2;+0:4]-[NH;D2;+0:9]-[C:7](-[C;D1;H3:6])-[C;D1;H3:8]
73
[{"value": 73.0, "product": "O[C@H](COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)CNC(C)C", "details": "PERCENTYIELD", "is_desired": false}]
75
CELSIUS
18
HOUR
A mixture of (2S)-6-methoxy-4-(2-methylindol-5-yloxy)-7-(oxiran-2-ylmethoxy)quinazoline (250 mg, 0.66 m.mol), (prepared as described for the starting material in Example 304), and isopropylamine (1.5 ml) in THF (10 ml) was stirred at 75° C. for 18 hours under an atmosphere of nitrogen and then allowed to cool to ambien...
10.6084/m9.figshare.5104873.v1
null
Ether.Primary amine
Secondary alcohol.Secondary amine
C1CO1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
null
C1CCOC1
75
18
CC(C)N.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@@H]1CO1>C1CCOC1>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@@H](O)CNC(C)C
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e77f24628f9d42b98aee2741e0f2b855
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@H]1CO1>>COc1ccc2ncnc(Oc3ccc4[nH]c(C)cc4c3)c2c1
COC=1C=C2C(=NC=NC2=CC1OC[C@@H]1OC1)OC=1C=C2C=C(NC2=CC1)C.C(C)(C)N>>COC=1C=C2C(=NC=NC2=CC1)OC=1C=C2C=C(NC2=CC1)C
C1O[C@H]1CO[c:4]1[c:3]([O:2][CH3:1])[cH:23][c:22]2[c:6]([cH:5]1)[n:7][cH:8][n:9][c:10]2[O:11][c:12]1[cH:13][cH:14][c:15]2[nH:16][c:17]([CH3:18])[cH:19][c:20]2[cH:21]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[n:7][cH:8][n:9][c:10]([O:11][c:12]3[cH:13][cH:14][c:15]4[nH:16][c:17]([CH3:18])[cH:19][c:20]4[cH:21]3)[c:22]2[cH:23...
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@H]1CO1
COc1ccc2ncnc(Oc3ccc4[nH]c(C)cc4c3)c2c1
null
null
C1CCOC1
Reduction
OtherReaction
a7bf2d7147ce1e3758997759ed14aac4b01a32af045af979a1c7bac98056e4bd
1556a72485df4201aca96fb7a0c321edf07cb063300030d429a36e916471ff2c
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
[#8:1]-[c:2]1:[c:3]:[c:4]2:[c:5]:[#7;a:6]:[c:7]:[#7;a:8]:[c:9]:2:[c:10]:[c;H0;D3;+0:11]:1-O-C-[C@@H]1-C-O-1>>[#8:1]-[c:2]1:[c:3]:[c:4]2:[c:5]:[#7;a:6]:[c:7]:[#7;a:8]:[c:9]:2:[c:10]:[cH;D2;+0:11]:1
120.6
[{"value": 84.0, "product": "COC=1C=C2C(=NC=NC2=CC1)OC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 120.6, "product": "COC=1C=C2C(=NC=NC2=CC1)OC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
75
CELSIUS
18
HOUR
A mixture of (2R)-6-methoxy-4-(2-methylindol-5-yloxy)-7-(oxiran-2-ylmethoxy)quinazoline (250 mg, 0.66 mmol), (prepared as described for the starting material in Example 269), and isopropylamine (1.5 ml) in THF (10 ml) was stirred at 75° C. for 18 hours under an atmosphere of nitrogen and then allowed to cool to ambient...
10.6084/m9.figshare.5104873.v1
null
Ether.Ether
null
C1CO1.c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.c1ccc2[nH]ccc2c1
HO-
C1CCOC1
75
18
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@H]1CO1>C1CCOC1>COc1ccc2ncnc(Oc3ccc4[nH]c(C)cc4c3)c2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e3297ced1472471fa98833a100debdfe
COc1cc2c(Cl)ncnc2cc1OCCN1CCCCC1.Cn1ccc2cc(O)ccc21>>COc1cc2c(Oc3ccc4c(ccn4C)c3)ncnc2cc1OCC(C)N1CCCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCN1CCCCC1.C([O-])([O-])=O.[K+].[K+].OC=1C=C2C=CN(C2=CC1)C>>COC=1C=C2C(=NC=NC2=CC1OCC(C)N1CCCCC1)OC=1C=C2C=CN(C2=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][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[c:12]([cH:13][cH:14][n:15]2[CH3:16])[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[c:12]([cH:13][cH:14][...
COc1cc2c(Cl)ncnc2cc1OCCN1CCCCC1.Cn1ccc2cc(O)ccc21
COc1cc2c(Oc3ccc4c(ccn4C)c3)ncnc2cc1OCC(C)N1CCCCC1
null
null
CC(=O)N(C)C
Heteroatom Alkylation and Arylation
OtherReaction
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCN3CCCCC3)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].[#8:9]-[C:10]-[CH2;D2;+0:11]-[#7:12](-[C:13])-[C:14].[OH;D1;+0:15]-[c:16](:[c:17]):[c:18]>>[#8:9]-[C:10]-[CH;D3;+0:11](-[C;D1;H3:19])-[#7:12](-[C:13])-[C:14].[c:17]:[c:16](-[O;H0;D2;+0:15]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:...
83
[{"value": 83.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCC(C)N1CCCCC1)OC=1C=C2C=CN(C2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 80.7, "product": "COC=1C=C2C(=NC=NC2=CC1OCC(C)N1CCCCC1)OC=1C=C2C=CN(C2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
90
CELSIUS
3
HOUR
Nitrogen was bubbled through a mixture of 4-chloro-6-methoxy-7-(2-piperidinoethoxy)quinazoline (400 mg, 1.24 mmol), (prepared as described for the starting material in Example 180), potassium carbonate (500 mg, 3.62 mmol), 5-hydroxy-1-methylindole (231 mg, 1.57 mmol), (prepared as described for the starting material in...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
null
CC(=O)N(C)C
90
3
COc1cc2c(Cl)ncnc2cc1OCCN1CCCCC1.Cn1ccc2cc(O)ccc21>CC(=O)N(C)C>COc1cc2c(Oc3ccc4c(ccn4C)c3)ncnc2cc1OCC(C)N1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-db4326c8d5f24bc4a6171f81adaa1aae
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cn1ccc2cc(O)ccc21>>COc1cc2c(Oc3ccc4c(ccn4C)c3)ncnc2cc1OCCCN1CCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1.C([O-])([O-])=O.[K+].[K+].OC=1C=C2C=CN(C2=CC1)C>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCC1)OC=1C=C2C=CN(C2=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]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[c:12]([cH:13][cH:14][n:15]2[CH3:16])[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[c:12]([cH:13][cH:14][...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cn1ccc2cc(O)ccc21
COc1cc2c(Oc3ccc4c(ccn4C)c3)ncnc2cc1OCCCN1CCCC1
null
null
CC(=O)N(C)C
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]
46.1
[{"value": 44.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCC1)OC=1C=C2C=CN(C2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 46.1, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCC1)OC=1C=C2C=CN(C2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
90
CELSIUS
3
HOUR
Nitrogen was bubbled through a mixture of 4-chloro-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline (400 mg, 1.24 mmol), (prepared as described for the starting material in Example 9), potassium carbonate (500 mg, 3.62 mmol), 5-hydroxy-1-methylindole (231 mg, 1.57 mmol), (prepared as described for the starting mater...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]C1
HCl
CC(=O)N(C)C
90
3
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cn1ccc2cc(O)ccc21>CC(=O)N(C)C>COc1cc2c(Oc3ccc4c(ccn4C)c3)ncnc2cc1OCCCN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-5765a1308ef94c4a807537fe1e5994c7
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.O=[N+]([O-])c1c(O)ccc2[nH]ccc12>>COc1cc2cnc(Oc3ccc4[nH]ccc4c3[N+](=O)[O-])nc2cc1OCCCN1CCCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1.C([O-])([O-])=O.[K+].[K+].OC=1C(=C2C=CNC2=CC1)[N+](=O)[O-]>>COC=1C=C2C=NC(=NC2=CC1OCCCN1CCCCC1)OC=1C(=C2C=CNC2=CC1)[N+](=O)[O-]
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][CH2:35]3)[cH:24][c:23]2[n:22][cH:8][n:7]1.[OH:9][c:10]1[cH:11][cH:12][c:13]2[nH:14][cH:15][cH:16][c:17]2[c:18]1[N+:19](=[O:20])[O-:21]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[cH:6][n:7][c:8]([O:9][c:10]3[cH:11][c...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.O=[N+]([O-])c1c(O)ccc2[nH]ccc12
COc1cc2cnc(Oc3ccc4[nH]ccc4c3[N+](=O)[O-])nc2cc1OCCCN1CCCCC1
null
null
CC(=O)N(C)C
Heteroatom Alkylation and Arylation
OtherReaction
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1cc2cc(Oc3ncc4ccc(OCCCN5CCCCC5)cc4n3)ccc2[nH]1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[cH;D2;+0:3]:[#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;+0:3]1:[#7;a:4]:[c:5](:[c:6]):[c:7](:[c:8]):[cH;D2;+0:1]:[#7;a:2]:1):[c:12]
39
[{"value": 39.0, "product": "COC=1C=C2C=NC(=NC2=CC1OCCCN1CCCCC1)OC=1C(=C2C=CNC2=CC1)[N+](=O)[O-]", "details": "PERCENTYIELD", "is_desired": false}, {"value": 38.8, "product": "COC=1C=C2C=NC(=NC2=CC1OCCCN1CCCCC1)OC=1C(=C2C=CNC2=CC1)[N+](=O)[O-]", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
90
CELSIUS
4
HOUR
Nitrogen was bubbled through a mixture of 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (114 mg, 0.34 mmol), (prepared as described for the starting material in Example 67), potassium carbonate (141 mg, 1.02 mmol), 5-hydroxy-4-nitroindole (60.5 mg, 0.34 mmol) and DMA (8.5 ml) for 5 minutes at ambient temperatur...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.c1ccc2[nH]ccc2c1.C1CC[NH]CC1
HCl
CC(=O)N(C)C
90
4
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.O=[N+]([O-])c1c(O)ccc2[nH]ccc12>CC(=O)N(C)C>COc1cc2cnc(Oc3ccc4[nH]ccc4c3[N+](=O)[O-])nc2cc1OCCCN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-c0d5244af2d04652bf6b3bc60250d25d
CCOC(=O)c1cc2cc(OC)ccc2[nH]1.O=[N+]([O-])O>>CCOC(=O)c1cc2c([N+](=O)[O-])c(O)ccc2[nH]1
COC=1C=C2C=C(NC2=CC1)C(=O)OCC.[N+](=O)(O)[O-]>>OC=1C(=C2C=C(NC2=CC1)C(=O)OCC)[N+](=O)[O-]
C[O:14][c:13]1[cH:9][c:8]2[cH:7][c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[nH:18][c:17]2[cH:16][cH:15]1.O[N+:10](=[O:11])[O-:12]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]2[c:9]([N+:10](=[O:11])[O-:12])[c:13]([OH:14])[cH:15][cH:16][c:17]2[nH:18]1
CCOC(=O)c1cc2cc(OC)ccc2[nH]1.O=[N+]([O-])O
CCOC(=O)c1cc2c([N+](=O)[O-])c(O)ccc2[nH]1
null
null
ClCCl
Functional Group Addition
OtherReaction
1b904b66dbdc426f37ef7cd0648bda460f21989aad8a862180f4279d1c37170a
f578230051b5bbda6f1c97099de3ba8f9f59ebaead9a0df3d73d663aaddbaf27
c1ccc2[nH]ccc2c1
C-[O;H0;D2;+0:1]-[c:2]1:[c:3]:[c:4]:[c:5]2:[#7;a:6]:[c:7](-[C:8](-[#8:9])=[O;D1;H0:10]):[c:11]:[c:12]:2:[cH;D2;+0:13]:1.O-[N+;H0;D3:14](-[O;-;D1;H0:15])=[O;D1;H0:16]>>[#8:9]-[C:8](=[O;D1;H0:10])-[c:7]1:[#7;a:6]:[c:5]2:[c:4]:[c:3]:[c:2](-[OH;D1;+0:1]):[c;H0;D3;+0:13](-[N+;H0;D3:14](-[O;-;D1;H0:15])=[O;D1;H0:16]):[c:12]:...
59
[{"value": 59.0, "product": "OC=1C(=C2C=C(NC2=CC1)C(=O)OCC)[N+](=O)[O-]", "details": "PERCENTYIELD", "is_desired": false}]
null
null
18
HOUR
A mixture of ethyl 5-methoxyindole-2-carboxylate (8.15 g, 37.2 mmol), (prepared by the method described in Heterocycles Vol. 43, No. 2, p. 263–266), nitric acid adsorbed on silica gel (24 g) and dichloromethane (150 ml) was stirred at ambient temperature for 18 hours. The dichloromethane was removed in vacuo and the pr...
10.6084/m9.figshare.5104873.v1
null
Ether.Nitrate
Nitro group.Aromatic alcohol
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1
HO-
ClCCl
null
18
CCOC(=O)c1cc2cc(OC)ccc2[nH]1.O=[N+]([O-])O>ClCCl>CCOC(=O)c1cc2c([N+](=O)[O-])c(O)ccc2[nH]1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-1145bac0a8ef4d079a9ef6503c24f277
CCO.CCOC(=O)c1cc2c([N+](=O)[O-])c(O)ccc2[nH]1>>COc1ccc2[nH]c(C(=O)O)cc2c1[N+](=O)[O-]
OC=1C(=C2C=C(NC2=CC1)C(=O)OCC)[N+](=O)[O-].C(C)O.[OH-].[K+]>>COC=1C(=C2C=C(NC2=CC1)C(=O)O)[N+](=O)[O-]
OC[CH3:1].CC[O:11][C:9]([c:8]1[nH:7][c:6]2[cH:5][cH:4][c:3]([OH:2])[c:14]([N+:15](=[O:16])[O-:17])[c:13]2[cH:12]1)=[O:10]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[nH:7][c:8]([C:9](=[O:10])[OH:11])[cH:12][c:13]2[c:14]1[N+:15](=[O:16])[O-:17]
CCO.CCOC(=O)c1cc2c([N+](=O)[O-])c(O)ccc2[nH]1
COc1ccc2[nH]c(C(=O)O)cc2c1[N+](=O)[O-]
null
null
O
Heteroatom Alkylation and Arylation
OtherReaction
0db00e48ffe5800295c995015791d2855681eceda8c116b62320b3c2b225d830
9653d63179b641796999681486e0249947865421087fe94dd6954f3668089e9b
c1ccc2[nH]ccc2c1
C-C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]:[#7;a:5].[OH;D1;+0:6]-[c:7](:[c:8]):[c:9].O-C-[CH3;D1;+0:10]>>[#7;a:5]:[c:4]-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1].[CH3;D1;+0:10]-[O;H0;D2;+0:6]-[c:7](:[c:8]):[c:9]
null
[]
50
CELSIUS
1
HOUR
Ethyl 5-hydroxy-4-nitroindole-2-carboxylate (1.0 g, 3.8 mmol.) was suspended in a mixture of ethanol (20 ml) and water (5 ml). Potassium hydroxide (840 mg) was added and the mixture stirred at 50° C. under an atmosphere of nitrogen for 1 hour then cooled to ambient temperature. The solvent was evaporated in vacuo and t...
10.6084/m9.figshare.5104873.v1
null
Ester.Primary alcohol.Aromatic alcohol
Carboxylic acid.Ether
null
null
c1ccc2[nH]ccc2c1
HO-
O
50
1
CCO.CCOC(=O)c1cc2c([N+](=O)[O-])c(O)ccc2[nH]1>O>COc1ccc2[nH]c(C(=O)O)cc2c1[N+](=O)[O-]
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-f52778852eac4e26b387c74570a3fc2c
COc1ccc2[nH]c(C(=O)O)cc2c1[N+](=O)[O-]>>COc1ccc2[nH]ccc2c1[N+](=O)[O-]
COC=1C(=C2C=C(NC2=CC1)C(=O)O)[N+](=O)[O-].N1=CC=CC2=CC=CC=C12>>COC=1C(=C2C=CNC2=CC1)[N+](=O)[O-]
O=C(O)[c:8]1[nH:7][c:6]2[cH:5][cH:4][c:3]([O:2][CH3:1])[c:11]([N+:12](=[O:13])[O-:14])[c:10]2[cH:9]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[nH:7][cH:8][cH:9][c:10]2[c:11]1[N+:12](=[O:13])[O-:14]
COc1ccc2[nH]c(C(=O)O)cc2c1[N+](=O)[O-]
COc1ccc2[nH]ccc2c1[N+](=O)[O-]
null
[Cr](=O)([O-])[O-].[Cu+2]
null
Reduction
Decarboxylation
d5c4709a8d4e49fe37f49e81e5c384f60c93fbbbbfa4eb758c4725d90cd07b32
292164ffdf89eeb341ee9424f24084b252a703a26bb77721b558b0f8a8528c45
c1ccc2[nH]ccc2c1
O-C(=O)-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[c:4]:[c:5]:1>>[#7;a:2]1:[c:3]:[c:4]:[c:5]:[cH;D2;+0:1]:1
22
[{"value": 22.0, "product": "COC=1C(=C2C=CNC2=CC1)[N+](=O)[O-]", "details": "PERCENTYIELD", "is_desired": false}, {"value": 22.0, "product": "COC=1C(=C2C=CNC2=CC1)[N+](=O)[O-]", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
225
CELSIUS
40
MINUTE
The crude 5-methoxy-4-nitroindole-2-carboxylic acid (720 mg, 3.05 mmol), quinoline (9 ml) and copper chromite (180 mg) were stirred together. Nitrogen was gently bubbled through the mixture for 5 minutes, then the mixture was heated quickly to 225° C., and stirred at this temperature for 40 minutes under an atmosphere ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid
null
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1
Other
[Cr](=O)([O-])[O-].[Cu+2]
225
0.666667
COc1ccc2[nH]c(C(=O)O)cc2c1[N+](=O)[O-]>[Cr](=O)([O-])[O-].[Cu+2]>COc1ccc2[nH]ccc2c1[N+](=O)[O-]
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-4f5f842a0be1424da1f9c5ea19160161
COc1ccc2[nH]ccc2c1[N+](=O)[O-]>>O=[N+]([O-])c1c(O)ccc2[nH]ccc12
B(Br)(Br)Br.COC=1C(=C2C=CNC2=CC1)[N+](=O)[O-]>>OC=1C(=C2C=CNC2=CC1)[N+](=O)[O-]
C[O:6][c:5]1[c:4]([N+:2](=[O:1])[O-:3])[c:13]2[c:9]([cH:8][cH:7]1)[nH:10][cH:11][cH:12]2>>[O:1]=[N+:2]([O-:3])[c:4]1[c:5]([OH:6])[cH:7][cH:8][c:9]2[nH:10][cH:11][cH:12][c:13]12
COc1ccc2[nH]ccc2c1[N+](=O)[O-]
O=[N+]([O-])c1c(O)ccc2[nH]ccc12
null
null
ClCCl.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]
67
[{"value": 67.0, "product": "OC=1C(=C2C=CNC2=CC1)[N+](=O)[O-]", "details": "PERCENTYIELD", "is_desired": false}, {"value": 67.0, "product": "OC=1C(=C2C=CNC2=CC1)[N+](=O)[O-]", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
A solution of 5-methoxy-4-nitroindole (110 mg, 0.57 mmol) in dichloromethane (12 ml) was cooled to −30° C. under an atmosphere of nitrogen. Boron tribromide (0.74 ml of a 1M solution in dichloromethane, 0.74 mmol) was added dropwise then the mixture warmed to ambient temperature and stirred for 1 hour. The mixture was ...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1ccc2[nH]ccc2c1
Other
ClCCl.O
null
1
COc1ccc2[nH]ccc2c1[N+](=O)[O-]>ClCCl.O>O=[N+]([O-])c1c(O)ccc2[nH]ccc12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-52ecf86f5b8543e4b0f31151b76f850e
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1cnc2[nH]ccc2c1>>COc1cc2c(Oc3cnc4[nH]ccc4c3)ncnc2cc1OCCCN1CCCCC1
[OH-].[Na+].ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1.OC=1C=C2C(=NC1)NC=C2.C([O-])([O-])=O.[K+].[K+]>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCCC1)OC=1C=C2C(=NC1)NC=C2
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][n: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][n:10][c:11]4[nH:12][cH:13][cH:14][c:1...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1cnc2[nH]ccc2c1
COc1cc2c(Oc3cnc4[nH]ccc4c3)ncnc2cc1OCCCN1CCCCC1
null
null
ClCCl.CO.CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2cnc3[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].[#7;a:9]:[c:10]:[#7;a:11]:[c:12]:[c:13](-[OH;D1;+0:14]):[c:15]>>[#7;a:9]:[c:10]:[#7;a:11]:[c:12]:[c:13](-[O;H0;D2;+0:14]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:15]
20
[{"value": 20.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCCC1)OC=1C=C2C(=NC1)NC=C2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 19.7, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCCC1)OC=1C=C2C(=NC1)NC=C2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
95
CELSIUS
6
HOUR
A mixture of 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (227 mg, 0.68 mmol), (prepared as described for the starting material in Example 67), 5-hydroxy-1H-pyrrolo[2,3-b]pyridine (100 mg, 0.75 mmol), (prepared as described for the starting material in Example 182), and potassium carbonate (350 mg, 2.5 mmol) i...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1cnc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
ClCCl.CO.CN(C)C=O
95
6
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1cnc2[nH]ccc2c1>ClCCl.CO.CN(C)C=O>COc1cc2c(Oc3cnc4[nH]ccc4c3)ncnc2cc1OCCCN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-fb000c2447784f589143e866bd9835aa
BrCCCBr.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1O>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCCCBr
OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC.C([O-])([O-])=O.[K+].[K+].BrCCCBr>>BrCCCOC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC
Br[CH2:24][CH2:25][CH2:26][Br: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]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]>>[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...
BrCCCBr.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1O
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCCCBr
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]
66
[{"value": 66.0, "product": "BrCCCOC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 65.7, "product": "BrCCCOC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
50
CELSIUS
null
null
To a solution of 7-hydroxy-4-(1H-indol-5-yloxy)-6-methoxyquinazoline (1 g, 3.2 mmol), (prepared as described for the starting material in Example 107), in DMF (50 ml) was added powdered potassium carbonate (1.32 g, 9.6 mmol) and 1,3-dibromopropane (6.43 g, 32 mmol). The reaction was heated at 50° C. for 2 hours. The in...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
HBr
CN(C)C=O
50
null
BrCCCBr.COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1O>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OCCCBr
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-091fd8723b8d47c0be67dca1b6ab457d
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)C[C@@H]2CCC(=O)N2C)cc1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@@H]1CCC(=O)N1C
OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC.C([O-])([O-])=O.[K+].[K+].C1(=CC=C(C=C1)S(=O)(=O)C[C@@H]1CCC(N1C)=O)C>>COC=1C=C2C(=NC=NC2=CC1OC[C@@H]1CCC(N1C)=O)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)[CH2:25][C@@H:26]2[CH2:27][CH2:28][C:29](=[O:30])[N:31]2[CH3:32])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...
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)C[C@@H]2CCC(=O)N2C)cc1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@@H]1CCC(=O)N1C
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
b5213736859cf91483a02f350869986d9b7674724716adef8a5d7a4bbdb79574
3d107e624e135e10014c7bf413dd0be27e1e4488f039e545b94cb1680b764158
O=C1CC[C@@H](COc2ccc3c(Oc4ccc5[nH]ccc5c4)ncnc3c2)N1
C-c1:c:c:c(-S(=O)(=O)-[CH2;D2;+0:1]-[C:2](-[C:3])-[#7:4](-[C;D1;H3:5])-[C:6]=[O;D1;H0:7]):c:c:1.[#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]-[CH2;D2;+0:1]-[C:2](-[C:3])-[#7:4](-[C;D1;H3:5])-[C:6]=[O;D1;H0:7]):[c:13]
33
[{"value": 33.0, "product": "COC=1C=C2C(=NC=NC2=CC1OC[C@@H]1CCC(N1C)=O)OC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 33.0, "product": "COC=1C=C2C(=NC=NC2=CC1OC[C@@H]1CCC(N1C)=O)OC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
95
CELSIUS
null
null
To a solution of 7-hydroxy-6-methoxy-4-(2-methyl-1H-indol-5-yloxy)quinazoline (225 ml, 0.7 mmol), (prepared as described in Example 49), in DMF was added powdered potassium carbonate (290 mg, 2.1 mmol) and (5S)-5-(p-toluenesulphonylmethyl)-1-methyl-2-pyrrolidinone (340 mg, 1.2 mmol). The reaction was then heated at 95°...
10.6084/m9.figshare.5104873.v1
null
Tosylate.Aromatic alcohol
Ether
c1ccccc1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]C1
TsOH.HO-
CN(C)C=O
95
null
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)C[C@@H]2CCC(=O)N2C)cc1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@@H]1CCC(=O)N1C
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3e589ae133f241e1a9ea020855ba8f22
CI.Cc1ccc(S(=O)(=O)C[C@@H]2CCC(=O)N2)cc1>>Cc1ccc(S(=O)(=O)C[C@@H]2CCC(=O)N2C)cc1
C1(=CC=C(C=C1)S(=O)(=O)C[C@@H]1CCC(N1)=O)C.C(C)(C)[N-]C(C)C.[Li+].CI>>C1(=CC=C(C=C1)S(=O)(=O)C[C@@H]1CCC(N1C)=O)C
I[CH3:16].[CH3:1][c:2]1[cH:3][cH:4][c:5]([S:6](=[O:7])(=[O:8])[CH2:9][C@@H:10]2[CH2:11][CH2:12][C:13](=[O:14])[NH:15]2)[cH:17][cH:18]1>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([S:6](=[O:7])(=[O:8])[CH2:9][C@@H:10]2[CH2:11][CH2:12][C:13](=[O:14])[N:15]2[CH3:16])[cH:17][cH:18]1
CI.Cc1ccc(S(=O)(=O)C[C@@H]2CCC(=O)N2)cc1
Cc1ccc(S(=O)(=O)C[C@@H]2CCC(=O)N2C)cc1
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
690e4b0724ae1dabd29a2644ea50ad8e32ff966e664aef6e23814fa90ed6067d
0a16658309ac5595448433dd7ef49294830b145345df0b202ccd54727262e629
O=C1CC[C@@H](CS(=O)(=O)c2ccccc2)N1
I-[CH3;D1;+0:1].[C:2]-[C:3]1-[C:4]-[C:5]-[C:6](=[O;D1;H0:7])-[NH;D2;+0:8]-1>>[C:2]-[C:3]1-[C:4]-[C:5]-[C:6](=[O;D1;H0:7])-[N;H0;D3;+0:8]-1-[CH3;D1;+0:1]
40
[{"value": 40.0, "product": "C1(=CC=C(C=C1)S(=O)(=O)C[C@@H]1CCC(N1C)=O)C", "details": "PERCENTYIELD", "is_desired": false}]
-70
CELSIUS
null
null
(5S)-5-(p-Toluenesulphonylmethyl)-2-pyrrolidinone (0.8 g, 3 mmol) was dissolved in dry THF and cooled to −70° C. Lithium diisopropylamide was slowly added and the reaction stirred for 20 minutes before addition of methyl iodide (2 ml, excess). The reaction was allowed to warm to ambient temperature for over 2 hours. Th...
10.6084/m9.figshare.5104873.v1
null
Secondary amide
Tertiary amide
C1CCNC1
C1CC[NH]C1
c1ccccc1.C1CC[NH]C1
HI
C1CCOC1
-70
null
CI.Cc1ccc(S(=O)(=O)C[C@@H]2CCC(=O)N2)cc1>C1CCOC1>Cc1ccc(S(=O)(=O)C[C@@H]2CCC(=O)N2C)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-ccca3779f0a24329bf4eb55bf6dab69f
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)C[C@@H]2CCC(=O)N2)cc1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H]1CCC(=O)N1
OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC.C([O-])([O-])=O.C1(=CC=C(C=C1)S(=O)(=O)C[C@@H]1CCC(N1)=O)C>>N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OC[C@@H]1CCC(N1)=O
[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].Cc1ccc(S(=O)(=O)[CH2:24][C@@H:25]2[CH2:26][CH2:27][C:28](=[O:29])[NH:30]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][...
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)C[C@@H]2CCC(=O)N2)cc1
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H]1CCC(=O)N1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
b5213736859cf91483a02f350869986d9b7674724716adef8a5d7a4bbdb79574
3d107e624e135e10014c7bf413dd0be27e1e4488f039e545b94cb1680b764158
O=C1CC[C@@H](COc2ccc3c(Oc4ccc5[nH]ccc5c4)ncnc3c2)N1
C-c1:c:c:c(-S(=O)(=O)-[CH2;D2;+0:1]-[C:2](-[C:3])-[#7:4]-[C:5]=[O;D1;H0:6]):c:c:1.[#7;a:7]:[c:8]:[c:9]:[c:10](-[OH;D1;+0:11]):[c:12]>>[#7;a:7]:[c:8]:[c:9]:[c:10](-[O;H0;D2;+0:11]-[CH2;D2;+0:1]-[C:2](-[C:3])-[#7:4]-[C:5]=[O;D1;H0:6]):[c:12]
31
[{"value": 31.0, "product": "N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OC[C@@H]1CCC(N1)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 30.4, "product": "N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OC[C@@H]1CCC(N1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
null
null
To a solution of 7-hydroxy-4-(l H-indol-5-yloxy)-6-methoxyquinazoline (600 mg, 1.95 mmol), (prepared as described for the starting material in Example 107), in DMF (20 ml) was added powdered potassuim carbonate (540 mg, 3.9 mmol) and (5S)-5-(p-toluene-sulphonylmethyl)-2-pyrrolidinone (580 mg, 2.16 mmol). The reaction w...
10.6084/m9.figshare.5104873.v1
null
Tosylate.Aromatic alcohol
Ether
c1ccccc1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CCNC1
TsOH.HO-
CN(C)C=O
100
null
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)C[C@@H]2CCC(=O)N2)cc1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@@H]1CCC(=O)N1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-7539d0aa4a264d3aae2d635fb64cb2b5
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)C[C@H]2CCC(=O)N2)cc1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CCC(=O)N1
OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC.C([O-])([O-])=O.C1(=CC=C(C=C1)S(=O)(=O)C[C@H]1CCC(N1)=O)C>>N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OC[C@H]1CCC(N1)=O
[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].Cc1ccc(S(=O)(=O)[CH2:24][C@H:25]2[CH2:26][CH2:27][C:28](=[O:29])[NH:30]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...
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)C[C@H]2CCC(=O)N2)cc1
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CCC(=O)N1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
b5213736859cf91483a02f350869986d9b7674724716adef8a5d7a4bbdb79574
3d107e624e135e10014c7bf413dd0be27e1e4488f039e545b94cb1680b764158
O=C1CC[C@H](COc2ccc3c(Oc4ccc5[nH]ccc5c4)ncnc3c2)N1
C-c1:c:c:c(-S(=O)(=O)-[CH2;D2;+0:1]-[C:2](-[C:3])-[#7:4]-[C:5]=[O;D1;H0:6]):c:c:1.[#7;a:7]:[c:8]:[c:9]:[c:10](-[OH;D1;+0:11]):[c:12]>>[#7;a:7]:[c:8]:[c:9]:[c:10](-[O;H0;D2;+0:11]-[CH2;D2;+0:1]-[C:2](-[C:3])-[#7:4]-[C:5]=[O;D1;H0:6]):[c:12]
6.7
[{"value": 6.5, "product": "N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OC[C@H]1CCC(N1)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 6.7, "product": "N1C=CC2=CC(=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OC[C@H]1CCC(N1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
90
CELSIUS
null
null
To a solution of 7-hydroxy-4-(1H-indol-5-yloxy)-6-methoxyquinazoline (800 mg, 2.6 mmol), (prepared as described for the starting material in Example 107), in DMF (20 ml) was added powdered potassuim carbonate (1.08 g, 7.8 mmol) and (5R)-5-(p-toluenesulphonylmethyl)-2-pyrrolidinone (1.13 g, 4.2 mmol). The reaction was t...
10.6084/m9.figshare.5104873.v1
null
Tosylate.Aromatic alcohol
Ether
c1ccccc1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CCNC1
TsOH.HO-
CN(C)C=O
90
null
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)C[C@H]2CCC(=O)N2)cc1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC[C@H]1CCC(=O)N1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-f5c5f32b27054ef198d09aaf03cb0ca3
Cc1ccc(S(=O)(=O)Cl)cc1.O=C1CC[C@H](CO)N1>>Cc1ccc(S(=O)(=O)C[C@H]2CCC(=O)N2)cc1
OC[C@H]1CCC(N1)=O.C1(=CC=C(C=C1)S(=O)(=O)Cl)C>>C1(=CC=C(C=C1)S(=O)(=O)C[C@H]1CCC(N1)=O)C
Cl[S:6]([c:5]1[cH:4][cH:3][c:2]([CH3:1])[cH:17][cH:16]1)(=[O:7])=[O:8].O[CH2:9][C@H:10]1[CH2:11][CH2:12][C:13](=[O:14])[NH:15]1>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([S:6](=[O:7])(=[O:8])[CH2:9][C@H:10]2[CH2:11][CH2:12][C:13](=[O:14])[NH:15]2)[cH:16][cH:17]1
Cc1ccc(S(=O)(=O)Cl)cc1.O=C1CC[C@H](CO)N1
Cc1ccc(S(=O)(=O)C[C@H]2CCC(=O)N2)cc1
null
CN(C1=CC=NC=C1)C
C(Cl)Cl
Acylation
OtherReaction
d05d91207659f8fa672c205a316a670adfe2b92492fc9adad2ee3f241e574fb9
a7748b0f3b0eba3868d0cf03ae67721db046202accaaea9cadb4edbc96ec8768
O=C1CC[C@H](CS(=O)(=O)c2ccccc2)N1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6].O-[CH2;D2;+0:7]-[C:8](-[C:9])-[#7:10]-[C:11]=[O;D1;H0:12]>>[C:9]-[C:8](-[CH2;D2;+0:7]-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6])-[#7:10]-[C:11]=[O;D1;H0:12]
94.6
[{"value": 89.0, "product": "C1(=CC=C(C=C1)S(=O)(=O)C[C@H]1CCC(N1)=O)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 94.6, "product": "C1(=CC=C(C=C1)S(=O)(=O)C[C@H]1CCC(N1)=O)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
16
HOUR
To a solution of (5R)-5-hydroxymethyl-2-pyrrolidinone (5.0 g, 43 mmol) in methylene chloride (100 ml) was added 4-dimethylaminopyridine (15.7 g, 129 mmol) and p-toluenesulphonyl chloride (9.0 g, 47 mmol). The reaction was stirred at ambient temperature for 16 hours. The reaction was then washed with 1M hydrochloric aci...
10.6084/m9.figshare.5104873.v1
null
Tosylate.Primary alcohol.Sulfonyl halide
Tosylate
null
null
c1ccccc1.C1CCNC1
HCl
CN(C1=CC=NC=C1)C.C(Cl)Cl
null
16
Cc1ccc(S(=O)(=O)Cl)cc1.O=C1CC[C@H](CO)N1>CN(C1=CC=NC=C1)C.C(Cl)Cl>Cc1ccc(S(=O)(=O)C[C@H]2CCC(=O)N2)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-4c6b1ca87ff546b38b050ef8144bce4d
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)C[C@H]2CCC(=O)N2)cc1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@H]1CCC(=O)N1
C1(=CC=C(C=C1)S(=O)(=O)C[C@H]1CCC(N1)=O)C.C1(=CC=C(C=C1)S(=O)(=O)C[C@H]1CCC(N1)=O)C.CCOCC.C([O-])([O-])=O.[K+].[K+].CCOCC.OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC>>COC=1C=C2C(=NC=NC2=CC1OC[C@H]1CCC(N1)=O)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)[CH2:25][C@H:26]2[CH2:27][CH2:28][C:29](=[O:30])[NH:31]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](...
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)C[C@H]2CCC(=O)N2)cc1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@H]1CCC(=O)N1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
b5213736859cf91483a02f350869986d9b7674724716adef8a5d7a4bbdb79574
3d107e624e135e10014c7bf413dd0be27e1e4488f039e545b94cb1680b764158
O=C1CC[C@H](COc2ccc3c(Oc4ccc5[nH]ccc5c4)ncnc3c2)N1
C-c1:c:c:c(-S(=O)(=O)-[CH2;D2;+0:1]-[C:2](-[C:3])-[#7:4]-[C:5]=[O;D1;H0:6]):c:c:1.[#7;a:7]:[c:8]:[c:9]:[c:10](-[OH;D1;+0:11]):[c:12]>>[#7;a:7]:[c:8]:[c:9]:[c:10](-[O;H0;D2;+0:11]-[CH2;D2;+0:1]-[C:2](-[C:3])-[#7:4]-[C:5]=[O;D1;H0:6]):[c:12]
0.3
[{"value": 0.3, "product": "COC=1C=C2C(=NC=NC2=CC1OC[C@H]1CCC(N1)=O)OC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
4
HOUR
To a suspension of 7-hydroxy-6-methoxy-4-(2-methyl-1H-indol-5-yloxy)quinazoline (1.36 g, 4.24 mmol), (prepared as described in Example 49), in DMF (70 ml), was added potassium carbonate (2.34 g, 17.0 mmol, 4eq.) followed by (5R)-5-(p-toluenesulphonylmethyl)-2-pyrrolidinone (1.25 g, 4.66 mmol, 1.1 eq.), (prepared as des...
10.6084/m9.figshare.5104873.v1
null
Tosylate.Aromatic alcohol
Ether
c1ccccc1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CCNC1
TsOH.HO-
CN(C)C=O
null
4
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.Cc1ccc(S(=O)(=O)C[C@H]2CCC(=O)N2)cc1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OC[C@H]1CCC(=O)N1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-7fa8fae7a4d149c49ffe087d086ce4ad
COc1cc2c(Cl)ncnc2cc1OCCC1CCN(C)CC1.Cc1cc2c(F)c(O)ccc2[nH]1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OCCC1CCN(C)CC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCC1CCN(CC1)C.FC1=C2C=C(NC2=CC=C1O)C.C([O-])([O-])=O.[K+].[K+]>>FC1=C2C=C(NC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCC1CCN(CC1)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][CH:28]3[CH2:29][CH2:30][N:31]([CH3:32])[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[nH:12][c:13]([CH3:14])[cH:15][c:16]2[c:17]1[F: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[nH:12][...
COc1cc2c(Cl)ncnc2cc1OCCC1CCN(C)CC1.Cc1cc2c(F)c(O)ccc2[nH]1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OCCC1CCN(C)CC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCC3CCNCC3)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]
62.5
[{"value": 62.0, "product": "FC1=C2C=C(NC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCC1CCN(CC1)C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 62.5, "product": "FC1=C2C=C(NC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCC1CCN(CC1)C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
95
CELSIUS
3
HOUR
A solution of 4-chloro-6-methoxy-7-(2-(1-methylpiperidin-4-yl)ethoxy)quinazoline (1.22 g, 3.65 mmol), (prepared as described for the starting material in Example 241), 4-fluoro-5-hydroxy-2-methylindole (723 mg, 4.38 mmol), (prepared as described for the starting material in Example 237), in DMF (20 ml) containing potas...
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
95
3
COc1cc2c(Cl)ncnc2cc1OCCC1CCN(C)CC1.Cc1cc2c(F)c(O)ccc2[nH]1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OCCC1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-2efe1d4bfcb84a37bc4f0adf50145c88
COc1cc2ncnc(Cl)c2cc1OC.Cc1nc2ccc(O)cc2[nH]1>>COc1cc2ncnc(Oc3ccc4nc(C)[nH]c4c3)c2cc1OC
[H-].[Na+].OC1=CC2=C(N=C(N2)C)C=C1.ClC1=NC=NC2=CC(=C(C=C12)OC)OC>>COC=1C=C2C(=NC=NC2=CC1OC)OC=1C=CC2=C(NC(=N2)C)C1
Cl[c:9]1[n:8][cH:7][n:6][c:5]2[cH:4][c:3]([O:2][CH3:1])[c:23]([O:24][CH3:25])[cH:22][c:21]21.[OH:10][c:11]1[cH:12][cH:13][c:14]2[n:15][c:16]([CH3:17])[nH:18][c:19]2[cH:20]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[n:6][cH:7][n:8][c:9]([O:10][c:11]3[cH:12][cH:13][c:14]4[n:15][c:16]([CH3:17])[nH:18][c:19]4[cH:20]3)[c:21]2[cH:22][...
COc1cc2ncnc(Cl)c2cc1OC.Cc1nc2ccc(O)cc2[nH]1
COc1cc2ncnc(Oc3ccc4nc(C)[nH]c4c3)c2cc1OC
null
null
O.CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1ccc2c(Oc3ccc4nc[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]
48.4
[{"value": 48.0, "product": "COC=1C=C2C(=NC=NC2=CC1OC)OC=1C=CC2=C(NC(=N2)C)C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 48.4, "product": "COC=1C=C2C(=NC=NC2=CC1OC)OC=1C=CC2=C(NC(=N2)C)C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
10
MINUTE
Sodium hydride (71 mg, 1.8 mmol) was added to 5-hydroxy-2-methylbenzimidazole (204 mg, 0.89 mmol) in anhydrous DMF (2.5 ml) under an argon atmosphere. The mixture was stirred at ambient temperature for 10 minutes. 4-Chloro-6,7-dimethoxyquinazoline (200 mg, 0.89 mmol) was added and the reaction mixture stirred at 95° C....
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.c1ccc2[nH]cnc2c1
HCl
O.CN(C)C=O
null
0.166667
COc1cc2ncnc(Cl)c2cc1OC.Cc1nc2ccc(O)cc2[nH]1>O.CN(C)C=O>COc1cc2ncnc(Oc3ccc4nc(C)[nH]c4c3)c2cc1OC
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-ff90139e3e3341ec989ad20a872b2f67
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Oc1ccc2cncnc2c1>>COc1cc2c(Oc3ccc4cncnc4c3)ncnc2cc1OCCCN1CCOCC1
[Cl-].[NH4+].OC1=CC=C2C=NC=NC2=C1.C([O-])([O-])=O.[K+].[K+].ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)OC1=CC=C2C=NC=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][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][n: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][n:13][cH:14]...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Oc1ccc2cncnc2c1
COc1cc2c(Oc3ccc4cncnc4c3)ncnc2cc1OCCCN1CCOCC1
null
null
CN(C)C=O.C(C)(=O)OCC
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1ncc2ccc(Oc3ncnc4cc(OCCCN5CCOCC5)ccc34)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]
83.1
[{"value": 83.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)OC1=CC=C2C=NC=NC2=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 83.1, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)OC1=CC=C2C=NC=NC2=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
null
null
7-Hydroxyquinazoline (87 mg, 0.6 mmol) and potassium carbonate (110 mg, 0.8 mmol) were added to 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (180 mg, 0.53 mmol), prepared as described for the starting material in Example 1), in suspension in DMF (3 ml) under an argon atmosphere. The reaction mixture was heated...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.c1ccc2ncncc2c1.C1COCC[NH]1
HCl
CN(C)C=O.C(C)(=O)OCC
100
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Oc1ccc2cncnc2c1>CN(C)C=O.C(C)(=O)OCC>COc1cc2c(Oc3ccc4cncnc4c3)ncnc2cc1OCCCN1CCOCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-ca3a6afb71df4486a504fc70cf734f4e
COc1cc2c(Nc3ccc4cc[nH]c4c3)ncnc2cc1O.Cc1ncsc1CCO>>COc1cc2c(Nc3ccc4cc[nH]c4c3)ncnc2cc1OCCc1scnc1C
OC1=C(C=C2C(=NC=NC2=C1)NC1=CC=C2C=CNC2=C1)OC.OCCC1=C(N=CS1)C>>COC=1C=C2C(=NC=NC2=CC1OCCC1=C(N=CS1)C)NC1=CC=C2C=CNC2=C1
[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[cH:12][cH:13][nH:14][c:15]4[cH:16]3)[n:17][cH:18][n:19][c:20]2[cH:21][c:22]1[OH:23].O[CH2:24][CH2:25][c:26]1[s:27][cH:28][n:29][c:30]1[CH3:31]>>[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[cH:12][cH:13][nH:14][c:15]4[cH:16]3)[n...
COc1cc2c(Nc3ccc4cc[nH]c4c3)ncnc2cc1O.Cc1ncsc1CCO
COc1cc2c(Nc3ccc4cc[nH]c4c3)ncnc2cc1OCCc1scnc1C
null
null
null
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1nc(Nc2ccc3cc[nH]c3c2)c2ccc(OCCc3cncs3)cc2n1
O-[CH2;D2;+0:1]-[C:2]-[c:3](:[#16;a:4]):[c:5]:[#7;a:6].[#7;a:7]:[c:8]:[c:9]:[c:10](-[OH;D1;+0:11]):[c:12]>>[#16;a:4]:[c:3](-[C:2]-[CH2;D2;+0:1]-[O;H0;D2;+0:11]-[c:10](:[c:12]):[c:9]:[c:8]:[#7;a:7]):[c:5]:[#7;a:6]
34
[{"value": 34.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCC1=C(N=CS1)C)NC1=CC=C2C=CNC2=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 34.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCC1=C(N=CS1)C)NC1=CC=C2C=CNC2=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 201, 7-hydroxy-4-(indol-6-ylamino)-6-methoxyquinazoline (98 mg, 0.32 mmol), (prepared as described for the starting material in Example 217), was reacted with 5-(2-hydroxyethyl)-4-methylthiazole (69 mg, 0.48 mmol) to give 6-methoxy-4-(indol-6-ylamino)-7-(2-(4-me...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.c1cscn1
HO-
null
null
null
COc1cc2c(Nc3ccc4cc[nH]c4c3)ncnc2cc1O.Cc1ncsc1CCO>>COc1cc2c(Nc3ccc4cc[nH]c4c3)ncnc2cc1OCCc1scnc1C
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-11a86478d050482fabbb54c90edeca53
COCCOCCOCCO.O=C(Cl)C1CC1>>COCCOCCOCCOC(=O)C1CC1
COCCOCCOCCO.C(C)N(CC)CC.C1(CC1)C(=O)Cl>>C1(CC1)C(=O)OCCOCCOCCOC
[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][CH2:7][O:8][CH2:9][CH2:10][OH:11].Cl[C:12](=[O:13])[CH:14]1[CH2:15][CH2:16]1>>[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][CH2:7][O:8][CH2:9][CH2:10][O:11][C:12](=[O:13])[CH:14]1[CH2:15][CH2:16]1
COCCOCCOCCO.O=C(Cl)C1CC1
COCCOCCOCCOC(=O)C1CC1
null
null
ClCCl
Acylation
Schotten-Baumann to ester
6cefe709828c5bd4655f254e75d5dff9e8876e192e7dd47256c1bc0067bc5291
d8a7643b81ed07a6f633aa99465180dfa0565e61ae25aef36338ebb9837c9cef
C1CC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]1-[C:4]-[C:5]-1.[C:6]-[C:7]-[OH;D1;+0:8]>>[C:6]-[C:7]-[O;H0;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]1-[C:4]-[C:5]-1
null
[]
0
CELSIUS
null
null
Triethylene glycol monomethyl ether (1.1 eq, 5.26 mmol, 0.84 ml) and triethylamine (1.1 eq, 5.26 mmol, 0.73 ml) were taken in a 10 ml round bottom flask and dichloromethane (3 ml) was added. This mixture was cooled to 0° C. and then cyclopropanecarbonyl chloride (4.78 mmol, 0.5 g, 0.43 ml) was added in a dropwise fashi...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary alcohol
Ester
null
null
C1CC1
HCl
ClCCl
0
null
COCCOCCOCCO.O=C(Cl)C1CC1>ClCCl>COCCOCCOCCOC(=O)C1CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3ba2ecbc665a4759aaf5991b901205ae
O=C(O)C1(c2ccccc2)CC1.O=S(Cl)Cl>>O=C(Cl)C1(c2ccccc2)CC1
C1(=CC=CC=C1)C1(CC1)C(=O)O.S(=O)(Cl)Cl>>C1(=CC=CC=C1)C1(CC1)C(=O)Cl
O[C:2](=[O:1])[C:4]1([c:5]2[cH:6][cH:7][cH:8][cH:9][cH:10]2)[CH2:11][CH2:12]1.O=S(Cl)[Cl:3]>>[O:1]=[C:2]([Cl:3])[C:4]1([c:5]2[cH:6][cH:7][cH:8][cH:9][cH:10]2)[CH2:11][CH2:12]1
O=C(O)C1(c2ccccc2)CC1.O=S(Cl)Cl
O=C(Cl)C1(c2ccccc2)CC1
null
null
null
Functional Group Interconversion
Alcohol to chloride_SOCl2
c301c14a9dcd0670d52e8b77396cbe7fd8edeedd757bc43f4162ade1fc52fc93
787f545db5dc0b29dde55b5fbed7db8625b8055f49327f97ed4d83cc47c3af1d
c1ccc(C2CC2)cc1
Cl-S(=O)-[Cl;H0;D1;+0:1].O-[C;H0;D3;+0:2](=[O;D1;H0:3])-[C:4]1(-[c:5])-[C:6]-[C:7]-1>>[Cl;H0;D1;+0:1]-[C;H0;D3;+0:2](=[O;D1;H0:3])-[C:4]1(-[c:5])-[C:6]-[C:7]-1
null
[]
80
CELSIUS
null
null
1-Phenyl-cyclopropanecarboxylic acid (0.5 g, 3.1 mmol), was dissolved in thionyl chloride (10 eq, 0.031 mol, 3.68 g, 2.3 ml), and refluxed at 80° C. for 1.5 hours. Then excess of thionyl chloride was evaporated on the rotary evaporator which yielded a dark-yellowish liquid (1-phenyl-cyclopropanecarbonyl chloride A), wh...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid
Acyl halide
null
null
c1ccccc1.C1CC1
HCl
null
80
null
O=C(O)C1(c2ccccc2)CC1.O=S(Cl)Cl>>O=C(Cl)C1(c2ccccc2)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-48a20edaaea94c4a9632062988784803
CC(C)(C)OC(=O)Nc1cccc(O)c1.N#Cc1ccc(CCO)cc1>>CC(C)(C)OC(=O)Nc1cccc(OCCc2ccc(C#N)cc2)c1
C(C)(C)(C)OC(=O)NC1=CC(=CC=C1)O.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.C(#N)C1=CC=C(C=C1)CCO.CCOC(=O)/N=N/C(=O)OCC>>C(C)(C)(C)OC(=O)NC1=CC(=CC=C1)OCCC1=CC=C(C=C1)C#N
[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][c:9]1[cH:10][cH:11][cH:12][c:13]([OH:14])[cH:25]1.O[CH2:15][CH2:16][c:17]1[cH:18][cH:19][c:20]([C:21]#[N:22])[cH:23][cH:24]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[NH:8][c:9]1[cH:10][cH:11][cH:12][c:13]([O:14][CH2:15][CH2:16][c:17]2[cH:18][cH:19][c:20]([...
CC(C)(C)OC(=O)Nc1cccc(O)c1.N#Cc1ccc(CCO)cc1
CC(C)(C)OC(=O)Nc1cccc(OCCc2ccc(C#N)cc2)c1
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1ccc(CCOc2ccccc2)cc1
O-[CH2;D2;+0:1]-[C:2]-[c:3].[OH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[c:6]:[c:5](-[O;H0;D2;+0:4]-[CH2;D2;+0:1]-[C:2]-[c:3]):[c:7]
44.3
[{"value": 44.0, "product": "C(C)(C)(C)OC(=O)NC1=CC(=CC=C1)OCCC1=CC=C(C=C1)C#N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 44.3, "product": "C(C)(C)(C)OC(=O)NC1=CC(=CC=C1)OCCC1=CC=C(C=C1)C#N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a solution of t-butyloxycarbonylamino-3-hydroxybenzene (418.5 mg; 2 mmol; from step (i) above), triphenylphosphine (629.5 mg; 2.4 mmol) and 2-(4-cyanophenyl)ethanol (353.2 mg; 2.4 mmol) in THF (50 mL), under an atmosphere of nitrogen, was added diethylazodicarboxylate (518 mg; 3 mmol) and the mixture was stirred for...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccccc1.c1ccccc1
HO-
C1CCOC1
null
null
CC(C)(C)OC(=O)Nc1cccc(O)c1.N#Cc1ccc(CCO)cc1>C1CCOC1>CC(C)(C)OC(=O)Nc1cccc(OCCc2ccc(C#N)cc2)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d2d5645ed5dc43bbb38599504ef9cde2
N#Cc1ccc(CCOc2cccc(N)c2)cc1.O=S(=O)(Cl)c1ccccc1>>N#Cc1ccc(CCOc2cccc(NS(=O)(=O)c3ccccc3)c2)cc1
O.NC1=CC(=CC=C1)OCCC1=CC=C(C=C1)C#N.Cl.C1(=CC=CC=C1)S(=O)(=O)Cl>>C(#N)C1=CC=C(C=C1)CCOC=1C=C(C=CC1)NS(=O)(=O)C1=CC=CC=C1
[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][CH2:8][O:9][c:10]2[cH:11][cH:12][cH:13][c:14]([NH2:15])[cH:25]2)[cH:26][cH:27]1.Cl[S:16](=[O:17])(=[O:18])[c:19]1[cH:20][cH:21][cH:22][cH:23][cH:24]1>>[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][CH2:8][O:9][c:10]2[cH:11][cH:12][cH:13][c:14]([NH:15][S:16](=[O:17])(=[O:18])[c:19]...
N#Cc1ccc(CCOc2cccc(N)c2)cc1.O=S(=O)(Cl)c1ccccc1
N#Cc1ccc(CCOc2cccc(NS(=O)(=O)c3ccccc3)c2)cc1
null
null
N1=CC=CC=C1
Acylation
Sulfonamide synthesis (Schotten-Baumann) primary amine
4c44ef6d7646f6ef25dd125d2c32c713d8dcae7c603407faa5f0fb810631670e
8fce8115d8a725afa92eb3910ded29d4c852e5133eba78a425054f41f7142603
O=S(=O)(Nc1cccc(OCCc2ccccc2)c1)c1ccccc1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6].[NH2;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[O;D1;H0:2]=[S;H0;D4;+0:1](=[O;D1;H0:3])(-[NH;D2;+0:7]-[c:8](:[c:9]):[c:10])-[c:4](:[c:5]):[c:6]
87
[{"value": 87.0, "product": "C(#N)C1=CC=C(C=C1)CCOC=1C=C(C=CC1)NS(=O)(=O)C1=CC=CC=C1", "details": "PERCENTYIELD", "is_desired": false}]
null
null
3
DAY
To a cold (ice:water temperature) solution of amino-3-[2-(4-cyanophenyl)ethoxy]benzene×HCl (231 mg; 0.84 mmol; from step (iii) above) in pyridine (2 mL) was added benzenesulfonyl chloride (119 μL; 0.93 mmol) and the mixture was allowed to reach room temperature and stirred for three days. The pyridine was removed by ev...
10.6084/m9.figshare.5104873.v1
null
Primary amine.Sulfonyl halide
Sulfonamide
null
null
c1ccccc1.c1ccccc1.c1ccccc1
HCl
N1=CC=CC=C1
null
72
N#Cc1ccc(CCOc2cccc(N)c2)cc1.O=S(=O)(Cl)c1ccccc1>N1=CC=CC=C1>N#Cc1ccc(CCOc2cccc(NS(=O)(=O)c3ccccc3)c2)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-ced6ed214bda408e923e0ec52746946f
N#Cc1ccc(CCO)cc1.O=[N+]([O-])c1cccc(O)c1>>N#Cc1ccc(CCOc2cccc([N+](=O)[O-])c2)cc1
C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.CCOC(=O)/N=N/C(=O)OCC.[N+](=O)([O-])C=1C=C(C=CC1)O.C(#N)C1=CC=C(C=C1)CCO>>[N+](=O)([O-])C1=CC(=CC=C1)OCCC1=CC=C(C=C1)C#N
O[CH2:8][CH2:7][c:6]1[cH:5][cH:4][c:3]([C:2]#[N:1])[cH:20][cH:19]1.[OH:9][c:10]1[cH:11][cH:12][cH:13][c:14]([N+:15](=[O:16])[O-:17])[cH:18]1>>[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][CH2:8][O:9][c:10]2[cH:11][cH:12][cH:13][c:14]([N+:15](=[O:16])[O-:17])[cH:18]2)[cH:19][cH:20]1
N#Cc1ccc(CCO)cc1.O=[N+]([O-])c1cccc(O)c1
N#Cc1ccc(CCOc2cccc([N+](=O)[O-])c2)cc1
null
null
O.C1CCOC1
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1ccc(CCOc2ccccc2)cc1
O-[CH2;D2;+0:1]-[C:2]-[c:3].[OH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[c:6]:[c:5](-[O;H0;D2;+0:4]-[CH2;D2;+0:1]-[C:2]-[c:3]):[c:7]
32
[{"value": 32.0, "product": "[N+](=O)([O-])C1=CC(=CC=C1)OCCC1=CC=C(C=C1)C#N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 31.9, "product": "[N+](=O)([O-])C1=CC(=CC=C1)OCCC1=CC=C(C=C1)C#N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
5
MINUTE
Triphenylphosphine (11.3 g; 43.1 mmol) and diethylazodicarboxylate (7.5 g; 43 mmol) were dissolved in THF (250 mL) under nitrogen at 0° C. After 5 minutes, 3-nitrophenol (5.00 g; 35.9 mmol) and 2-(4-cyanophenyl)ethanol (6.3 g; 43 mmol) were added. The cooling bath was removed and the mixture stirred for 2 days at room ...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccccc1.c1ccccc1
HO-
O.C1CCOC1
null
0.083333
N#Cc1ccc(CCO)cc1.O=[N+]([O-])c1cccc(O)c1>O.C1CCOC1>N#Cc1ccc(CCOc2cccc([N+](=O)[O-])c2)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b973abd038d94f0bb0ea1d8a4c1700bc
N#Cc1ccc(CCOc2cccc([N+](=O)[O-])c2)cc1>>N#Cc1ccc(CCOc2cccc(N)c2)cc1
[N+](=O)([O-])C1=CC(=CC=C1)OCCC1=CC=C(C=C1)C#N.[NH4+].[Cl-]>>NC1=CC(=CC=C1)OCCC1=CC=C(C=C1)C#N
O=[N+:15]([O-])[c:14]1[cH:13][cH:12][cH:11][c:10]([O:9][CH2:8][CH2:7][c:6]2[cH:5][cH:4][c:3]([C:2]#[N:1])[cH:18][cH:17]2)[cH:16]1>>[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][CH2:8][O:9][c:10]2[cH:11][cH:12][cH:13][c:14]([NH2:15])[cH:16]2)[cH:17][cH:18]1
N#Cc1ccc(CCOc2cccc([N+](=O)[O-])c2)cc1
N#Cc1ccc(CCOc2cccc(N)c2)cc1
null
[Fe]
O.CCO
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccc(CCOc2ccccc2)cc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
85
[{"value": 85.0, "product": "NC1=CC(=CC=C1)OCCC1=CC=C(C=C1)C#N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 84.7, "product": "NC1=CC(=CC=C1)OCCC1=CC=C(C=C1)C#N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
Nitro-3-[2-(4-cyanophenyl)ethoxy]benzene (3.0 g; 11.2 mmol; from step (i) above) and NH4Cl (2.9 g; 55 mmol) were dissolved in a mixture of EtOH (40 mL) and H2O (10 mL) and heated to reflux. Iron powder (3.0 g; 55 mmol) was added and heating was continued for 1 hour. The mixture was filtered, concentrated in vacuo and p...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccccc1.c1ccccc1
Other
[Fe].O.CCO
null
1
N#Cc1ccc(CCOc2cccc([N+](=O)[O-])c2)cc1>[Fe].O.CCO>N#Cc1ccc(CCOc2cccc(N)c2)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a07f8c5795414f378ef03facfd4bc52e
N#Cc1ccc(CCOc2cccc(N)c2)cc1.O=S(=O)(Cl)c1ccccc1Cl>>N#Cc1ccc(CCOc2cccc(NS(=O)(=O)c3ccccc3Cl)c2)cc1
N1=CC=CC=C1.NC1=CC(=CC=C1)OCCC1=CC=C(C=C1)C#N.ClC1=C(C=CC=C1)S(=O)(=O)Cl>>C(#N)C1=CC=C(C=C1)CCOC=1C=C(C=CC1)NS(=O)(=O)C1=C(C=CC=C1)Cl
[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][CH2:8][O:9][c:10]2[cH:11][cH:12][cH:13][c:14]([NH2:15])[cH:26]2)[cH:27][cH:28]1.Cl[S:16](=[O:17])(=[O:18])[c:19]1[cH:20][cH:21][cH:22][cH:23][c:24]1[Cl:25]>>[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][CH2:8][O:9][c:10]2[cH:11][cH:12][cH:13][c:14]([NH:15][S:16](=[O:17])(=[O:18])...
N#Cc1ccc(CCOc2cccc(N)c2)cc1.O=S(=O)(Cl)c1ccccc1Cl
N#Cc1ccc(CCOc2cccc(NS(=O)(=O)c3ccccc3Cl)c2)cc1
null
null
C(Cl)Cl
Acylation
Sulfonamide synthesis (Schotten-Baumann) primary amine
4c44ef6d7646f6ef25dd125d2c32c713d8dcae7c603407faa5f0fb810631670e
8fce8115d8a725afa92eb3910ded29d4c852e5133eba78a425054f41f7142603
O=S(=O)(Nc1cccc(OCCc2ccccc2)c1)c1ccccc1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6].[NH2;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[O;D1;H0:2]=[S;H0;D4;+0:1](=[O;D1;H0:3])(-[NH;D2;+0:7]-[c:8](:[c:9]):[c:10])-[c:4](:[c:5]):[c:6]
36.6
[{"value": 35.0, "product": "C(#N)C1=CC=C(C=C1)CCOC=1C=C(C=CC1)NS(=O)(=O)C1=C(C=CC=C1)Cl", "details": "PERCENTYIELD", "is_desired": false}, {"value": 36.6, "product": "C(#N)C1=CC=C(C=C1)CCOC=1C=C(C=CC1)NS(=O)(=O)C1=C(C=CC=C1)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Pyridine (0.255 mL; 3.15 mmol) was added to a stirred solution of amino-3-[2-(4-cyanophenyl)ethoxy]benzene (0.15 g; 0.629 mmol; from step (ii) above) and 2-chlorobenzenesulfonyl chloride (0.173 mL; 0.818 mmol) in CH2Cl2 (4 mL). After 45 minutes at room temperature the solvent was removed in vacuo. To remove traces of p...
10.6084/m9.figshare.5104873.v1
null
Primary amine.Sulfonyl halide
Sulfonamide
null
null
c1ccccc1.c1ccccc1.c1ccccc1
HCl
C(Cl)Cl
null
null
N#Cc1ccc(CCOc2cccc(N)c2)cc1.O=S(=O)(Cl)c1ccccc1Cl>C(Cl)Cl>N#Cc1ccc(CCOc2cccc(NS(=O)(=O)c3ccccc3Cl)c2)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-2823d9a23038452eb6617bd6e117c0d9
CC(C)(C)OC(=O)N=Cc1cc(N)ccc1CCOc1cccc([N+](=O)[O-])c1>>CC(C)(C)OC(=O)N=Cc1cc(N)ccc1CCOc1cccc(N)c1
NC1=CC(=C(C=C1)CCOC=1C=C(C=CC1)[N+](=O)[O-])C=NC(=O)OC(C)(C)C>>NC1=CC(=CC=C1)OCCC1=C(C=C(C=C1)N)C=NC(=O)OC(C)(C)C
O=[N+:25]([O-])[c:24]1[cH:23][cH:22][cH:21][c:20]([O:19][CH2:18][CH2:17][c:16]2[c:10]([CH:9]=[N:8][C:6]([O:5][C:2]([CH3:1])([CH3:3])[CH3:4])=[O:7])[cH:11][c:12]([NH2:13])[cH:14][cH:15]2)[cH:26]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[O:5][C:6](=[O:7])[N:8]=[CH:9][c:10]1[cH:11][c:12]([NH2:13])[cH:14][cH:15][c:16]1[CH2:17][CH2:...
CC(C)(C)OC(=O)N=Cc1cc(N)ccc1CCOc1cccc([N+](=O)[O-])c1
CC(C)(C)OC(=O)N=Cc1cc(N)ccc1CCOc1cccc(N)c1
null
[Pd]
CCO
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccc(CCOc2ccccc2)cc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
null
null
25
MINUTE
A suspension of 3-[2-(4-amino{t-butoxycarbonylimino}methylphenyl)-ethoxy]nitrobenzene (1.47 g; 3.81 mmol; from step (iii) above) and Pd (0.236 g; 5% on charcoal) in EtOH (75 mL) was stirred under H2(g) (1 atm.) for 25 minutes. After filtration through Celite the solvent was evaporated. The residue was purified by prepa...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccccc1.c1ccccc1
Other
[Pd].CCO
null
0.416667
CC(C)(C)OC(=O)N=Cc1cc(N)ccc1CCOc1cccc([N+](=O)[O-])c1>[Pd].CCO>CC(C)(C)OC(=O)N=Cc1cc(N)ccc1CCOc1cccc(N)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-7d57a165596141cbaf972e1129adb4f6
CC(C)(C)OC(=O)OC(C)(C)C.Cc1c(N)cccc1O>>Cc1c(O)cccc1NC(=O)OC(C)(C)C
NC=1C(=C(C=CC1)O)C.C(C)(C)(C)OC(OC(C)(C)C)=O>>C(C)(C)(C)OC(=O)NC=1C(=C(C=CC1)O)C
CC(C)(C)O[C:10](=[O:11])[O:12][C:13]([CH3:14])([CH3:15])[CH3:16].[CH3:1][c:2]1[c:3]([OH:4])[cH:5][cH:6][cH:7][c:8]1[NH2:9]>>[CH3:1][c:2]1[c:3]([OH:4])[cH:5][cH:6][cH:7][c:8]1[NH:9][C:10](=[O:11])[O:12][C:13]([CH3:14])([CH3:15])[CH3:16]
CC(C)(C)OC(=O)OC(C)(C)C.Cc1c(N)cccc1O
Cc1c(O)cccc1NC(=O)OC(C)(C)C
null
null
C1CCOC1
Protection
Boc amine protection of primary amine
f3c90cf52fa3def89ea52c9439021d67dcb4e78193592b513b9947b2ea03f400
b95329d3f436e956daff6cdf06b1d304d2b6f26b5a9f436cd33b2f3a6d7b99d2
c1ccccc1
C-C(-C)(-C)-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[C:4](-[C;D1;H3:5])(-[C;D1;H3:6])-[C;D1;H3:7].[NH2;D1;+0:8]-[c:9](:[c:10]):[c:11]>>[C;D1;H3:5]-[C:4](-[C;D1;H3:6])(-[C;D1;H3:7])-[#8:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:8]-[c:9](:[c:10]):[c:11]
69
[{"value": 69.0, "product": "C(C)(C)(C)OC(=O)NC=1C(=C(C=CC1)O)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
3-Amino-2-methylphenol (2.0 g; 16 mmol) and di-t-butylcarbonate were dissolved in THF (20 mL) and refluxed overnight. Evaporation of the solvent followed by flash chromatography (SiO2; EtOAc 5–30% in isohexane) afforded 2.48 g (69%) of the sub-title compound. Conditions: See reaction.notes.procedure_details. Workup: re...
10.6084/m9.figshare.5104873.v1
null
Carbonic Ester.Primary amine.Boc.Boc
Carbamic ester
null
null
c1ccccc1
HO-
C1CCOC1
null
null
CC(C)(C)OC(=O)OC(C)(C)C.Cc1c(N)cccc1O>C1CCOC1>Cc1c(O)cccc1NC(=O)OC(C)(C)C
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-6be99bc338074bd19cfef980b50197e0
Cc1c(O)cccc1NC(=O)OC(C)(C)C.N#Cc1ccc(CCO)cc1>>Cc1c(NC(=O)OC(C)(C)C)cccc1OCCc1ccc(C#N)cc1
C(#N)C1=CC=C(C=C1)CCO.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.CCOC(=O)/N=N/C(=O)OCC.C(C)(C)(C)OC(=O)NC=1C(=C(C=CC1)O)C>>C(C)(C)(C)OC(=O)NC1=C(C(=CC=C1)OCCC1=CC=C(C=C1)C#N)C
O[c:15]1[c:2]([CH3:1])[c:3]([NH:4][C:5](=[O:6])[O:7][C:8]([CH3:9])([CH3:10])[CH3:11])[cH:12][cH:13][cH:14]1.[OH:16][CH2:17][CH2:18][c:19]1[cH:20][cH:21][c:22]([C:23]#[N:24])[cH:25][cH:26]1>>[CH3:1][c:2]1[c:3]([NH:4][C:5](=[O:6])[O:7][C:8]([CH3:9])([CH3:10])[CH3:11])[cH:12][cH:13][cH:14][c:15]1[O:16][CH2:17][CH2:18][c:1...
Cc1c(O)cccc1NC(=O)OC(C)(C)C.N#Cc1ccc(CCO)cc1
Cc1c(NC(=O)OC(C)(C)C)cccc1OCCc1ccc(C#N)cc1
null
null
O.C1CCOC1
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
8915084acbaaf997bf0f89ff5187cb2f89c25dc683fffc57b3391298c8430dd9
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1ccc(CCOc2ccccc2)cc1
O-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[C;D1;H3:5]):[c:6].[C:7]-[C:8]-[OH;D1;+0:9]>>[C:7]-[C:8]-[O;H0;D2;+0:9]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[C;D1;H3:5]):[c:6]
77
[{"value": 77.0, "product": "C(C)(C)(C)OC(=O)NC1=C(C(=CC=C1)OCCC1=CC=C(C=C1)C#N)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 76.2, "product": "C(C)(C)(C)OC(=O)NC1=C(C(=CC=C1)OCCC1=CC=C(C=C1)C#N)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
Triphenylphosphine (1.31 g, 13.5 mmol) and diethylazodicarboxylate (1.7 mL) were dissolved in THF (20 mL) under nitrogen. After 15 minutes 3-t-butoxycarbonylamino-2-methylphenol (2.48 g; 11.1 mmol; from step (i) above) dissolved in THF (20 mL) and 2-(4-cyanophenyl)ethanol (1.9 g, 13 mmol) were added. After 5 days at ro...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HO-
O.C1CCOC1
null
0.5
Cc1c(O)cccc1NC(=O)OC(C)(C)C.N#Cc1ccc(CCO)cc1>O.C1CCOC1>Cc1c(NC(=O)OC(C)(C)C)cccc1OCCc1ccc(C#N)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-5072aaaf7af947d3ab046709fd2cf87e
Cc1c(NC(=O)OC(C)(C)C)cccc1OCCc1ccc(C#N)cc1>>Cc1c(N)cccc1OCCc1ccc(C#N)cc1
C(C)(C)(C)OC(=O)NC1=C(C(=CC=C1)OCCC1=CC=C(C=C1)C#N)C>>NC1=C(C(=CC=C1)OCCC1=CC=C(C=C1)C#N)C
CC(C)(C)OC(=O)[NH:4][c:3]1[c:2]([CH3:1])[c:8]([O:9][CH2:10][CH2:11][c:12]2[cH:13][cH:14][c:15]([C:16]#[N:17])[cH:18][cH:19]2)[cH:7][cH:6][cH:5]1>>[CH3:1][c:2]1[c:3]([NH2:4])[cH:5][cH:6][cH:7][c:8]1[O:9][CH2:10][CH2:11][c:12]1[cH:13][cH:14][c:15]([C:16]#[N:17])[cH:18][cH:19]1
Cc1c(NC(=O)OC(C)(C)C)cccc1OCCc1ccc(C#N)cc1
Cc1c(N)cccc1OCCc1ccc(C#N)cc1
null
null
Cl.CCOC(=O)C
Reduction
Hydrogenolysis of amides/imides/carbamates
3c33dd2a2d355ee5ba0287367e209aa147a39aa00607f0c95fb2bf1ade45d014
c5b5dffe7dd8beebdc1baa8b5b05300a9f7079e65dcfd42ade6f8a77ff09537d
c1ccc(CCOc2ccccc2)cc1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
21.8
[{"value": 19.0, "product": "NC1=C(C(=CC=C1)OCCC1=CC=C(C=C1)C#N)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 21.8, "product": "NC1=C(C(=CC=C1)OCCC1=CC=C(C=C1)C#N)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
t-Butoxycarbonylamino-3-[2-(4-cyanophenyl)ethoxy]-2-methylbenzene (2.69 g, 7.64 mmol; from step (ii) above) were dissolved in EtOAc, pre-saturated with HCl(g), (150 mL) under nitrogen and stirred at room temperature overnight. After evaporation of the solvent the residue was partitioned between 10% aqueous HCl and EtOA...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Primary amine
null
null
c1ccccc1.c1ccccc1
HO-
Cl.CCOC(=O)C
null
8
Cc1c(NC(=O)OC(C)(C)C)cccc1OCCc1ccc(C#N)cc1>Cl.CCOC(=O)C>Cc1c(N)cccc1OCCc1ccc(C#N)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e7aa3513f10e42e6a97b30503cbcad8b
Cc1c(N)cccc1OCCc1ccc(C#N)cc1.O=S(=O)(Cl)c1ccccc1>>Cc1c(NS(=O)(=O)c2ccccc2)cccc1OCCc1ccc(C#N)cc1
C1(=CC=CC=C1)S(=O)(=O)Cl.NC1=C(C(=CC=C1)OCCC1=CC=C(C=C1)C#N)C>>C(#N)C1=CC=C(C=C1)CCOC=1C(=C(C=CC1)NS(=O)(=O)C1=CC=CC=C1)C
[CH3:1][c:2]1[c:3]([NH2:4])[cH:14][cH:15][cH:16][c:17]1[O:18][CH2:19][CH2:20][c:21]1[cH:22][cH:23][c:24]([C:25]#[N:26])[cH:27][cH:28]1.Cl[S:5](=[O:6])(=[O:7])[c:8]1[cH:9][cH:10][cH:11][cH:12][cH:13]1>>[CH3:1][c:2]1[c:3]([NH:4][S:5](=[O:6])(=[O:7])[c:8]2[cH:9][cH:10][cH:11][cH:12][cH:13]2)[cH:14][cH:15][cH:16][c:17]1[O:...
Cc1c(N)cccc1OCCc1ccc(C#N)cc1.O=S(=O)(Cl)c1ccccc1
Cc1c(NS(=O)(=O)c2ccccc2)cccc1OCCc1ccc(C#N)cc1
null
null
N1=CC=CC=C1
Acylation
Sulfonamide synthesis (Schotten-Baumann) primary amine
4c44ef6d7646f6ef25dd125d2c32c713d8dcae7c603407faa5f0fb810631670e
8fce8115d8a725afa92eb3910ded29d4c852e5133eba78a425054f41f7142603
O=S(=O)(Nc1cccc(OCCc2ccccc2)c1)c1ccccc1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6].[NH2;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[O;D1;H0:2]=[S;H0;D4;+0:1](=[O;D1;H0:3])(-[NH;D2;+0:7]-[c:8](:[c:9]):[c:10])-[c:4](:[c:5]):[c:6]
72
[{"value": 72.0, "product": "C(#N)C1=CC=C(C=C1)CCOC=1C(=C(C=CC1)NS(=O)(=O)C1=CC=CC=C1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 70.4, "product": "C(#N)C1=CC=C(C=C1)CCOC=1C(=C(C=CC1)NS(=O)(=O)C1=CC=CC=C1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
Benzenesulfonyl chloride (0.24 mL; 1.9 mmol) was added to a stirred solution of amino-3-[2-(4-cyanophenyl)ethoxy]-2-methylbenzene (0.42 g ; 1.7 mmol; from step (iii) above) in dry pyridine (20 mL) under nitrogen. The reaction was left overnight at room temperature. After evaporation of the solvent the residue was parti...
10.6084/m9.figshare.5104873.v1
null
Primary amine.Sulfonyl halide
Sulfonamide
null
null
c1ccccc1.c1ccccc1.c1ccccc1
HCl
N1=CC=CC=C1
null
8
Cc1c(N)cccc1OCCc1ccc(C#N)cc1.O=S(=O)(Cl)c1ccccc1>N1=CC=CC=C1>Cc1c(NS(=O)(=O)c2ccccc2)cccc1OCCc1ccc(C#N)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-c02799cee8c540e594b36dee65c595a6
Cc1ccc(O)cc1[N+](=O)[O-].N#Cc1ccc(CCO)cc1>>Cc1ccc(OCCc2ccc(C#N)cc2)cc1[N+](=O)[O-]
CC1=C(C=C(C=C1)O)[N+](=O)[O-].C(#N)C1=CC=C(C=C1)CCO.CCOC(=O)/N=N/C(=O)OCC.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1>>C(#N)C1=CC=C(C=C1)CCOC1=CC(=C(C=C1)C)[N+](=O)[O-]
[CH3:1][c:2]1[cH:3][cH:4][c:5]([OH:6])[cH:17][c:18]1[N+:19](=[O:20])[O-:21].O[CH2:7][CH2:8][c:9]1[cH:10][cH:11][c:12]([C:13]#[N:14])[cH:15][cH:16]1>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([O:6][CH2:7][CH2:8][c:9]2[cH:10][cH:11][c:12]([C:13]#[N:14])[cH:15][cH:16]2)[cH:17][c:18]1[N+:19](=[O:20])[O-:21]
Cc1ccc(O)cc1[N+](=O)[O-].N#Cc1ccc(CCO)cc1
Cc1ccc(OCCc2ccc(C#N)cc2)cc1[N+](=O)[O-]
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1ccc(CCOc2ccccc2)cc1
O-[CH2;D2;+0:1]-[C:2]-[c:3].[OH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[c:6]:[c:5](-[O;H0;D2;+0:4]-[CH2;D2;+0:1]-[C:2]-[c:3]):[c:7]
null
[]
null
null
8
HOUR
4-Methyl-3-nitrophenol (0.765 g; 5.0 mmol), 2-(4-cyanophenyl)ethanol (0.735 g; 5.0 mmol) and diethylazodicarboxylate (0.87 g; 5.0 mmol) were dissolved in THF (20 mL). Triphenylphosphine (1.31 g; 5.0 mmol), dissolved in THF (5 mL), was added and the solution stirred overnight. Evaporation in vacuo and the addition of di...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccccc1.c1ccccc1
HO-
C1CCOC1
null
8
Cc1ccc(O)cc1[N+](=O)[O-].N#Cc1ccc(CCO)cc1>C1CCOC1>Cc1ccc(OCCc2ccc(C#N)cc2)cc1[N+](=O)[O-]
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-97967a60623a4f7b94a70e73c45afd80
Cc1ccc(OCCc2ccc(C#N)cc2)cc1[N+](=O)[O-]>>Cc1ccc(OCCc2ccc(C#N)cc2)cc1N
[BH4-].[Na+].C(#N)C1=CC=C(C=C1)CCOC1=CC(=C(C=C1)C)[N+](=O)[O-].CCOC(=O)C>>NC1=C(C=CC(=C1)OCCC1=CC=C(C=C1)C#N)C
O=[N+:19]([O-])[c:18]1[c:2]([CH3:1])[cH:3][cH:4][c:5]([O:6][CH2:7][CH2:8][c:9]2[cH:10][cH:11][c:12]([C:13]#[N:14])[cH:15][cH:16]2)[cH:17]1>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([O:6][CH2:7][CH2:8][c:9]2[cH:10][cH:11][c:12]([C:13]#[N:14])[cH:15][cH:16]2)[cH:17][c:18]1[NH2:19]
Cc1ccc(OCCc2ccc(C#N)cc2)cc1[N+](=O)[O-]
Cc1ccc(OCCc2ccc(C#N)cc2)cc1N
null
S(=O)(=O)([O-])[O-].[Cu+2]
CCO
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccc(CCOc2ccccc2)cc1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
26
[{"value": 26.0, "product": "NC1=C(C=CC(=C1)OCCC1=CC=C(C=C1)C#N)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 26.0, "product": "NC1=C(C=CC(=C1)OCCC1=CC=C(C=C1)C#N)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
Sodium borohydride (0.127 g; 3.35 mmol) was added in portions to a cold suspension (ice:water temperature) of [2-(4-cyanophenyl)ethoxy]-4-methyl-3-nitrobenzene (0.19 g; 0.67 mmol; from step (i) above) and aqueous copper sulfate (1.34 mL; 1 M; 1.34 mmol) in EtOH (5 mL) over five minutes. The temperature was allowed to r...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccccc1.c1ccccc1
Other
S(=O)(=O)([O-])[O-].[Cu+2].CCO
null
0.5
Cc1ccc(OCCc2ccc(C#N)cc2)cc1[N+](=O)[O-]>S(=O)(=O)([O-])[O-].[Cu+2].CCO>Cc1ccc(OCCc2ccc(C#N)cc2)cc1N
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b6cc1b52f1bd4a2782218856645c0bae
Cc1ccc(OCCc2ccc(C#N)cc2)cc1N.O=S(=O)(Cl)c1ccccc1>>Cc1ccc(OCCc2ccc(C#N)cc2)cc1NS(=O)(=O)c1ccccc1
C1(=CC=CC=C1)S(=O)(=O)Cl.NC1=C(C=CC(=C1)OCCC1=CC=C(C=C1)C#N)C.C(=O)(O)[O-].[Na+]>>C(#N)C1=CC=C(C=C1)CCOC=1C=CC(=C(C1)NS(=O)(=O)C1=CC=CC=C1)C
[CH3:1][c:2]1[cH:3][cH:4][c:5]([O:6][CH2:7][CH2:8][c:9]2[cH:10][cH:11][c:12]([C:13]#[N:14])[cH:15][cH:16]2)[cH:17][c:18]1[NH2:19].Cl[S:20](=[O:21])(=[O:22])[c:23]1[cH:24][cH:25][cH:26][cH:27][cH:28]1>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([O:6][CH2:7][CH2:8][c:9]2[cH:10][cH:11][c:12]([C:13]#[N:14])[cH:15][cH:16]2)[cH:17][c:18...
Cc1ccc(OCCc2ccc(C#N)cc2)cc1N.O=S(=O)(Cl)c1ccccc1
Cc1ccc(OCCc2ccc(C#N)cc2)cc1NS(=O)(=O)c1ccccc1
null
null
N1=CC=CC=C1
Acylation
Sulfonamide synthesis (Schotten-Baumann) primary amine
4c44ef6d7646f6ef25dd125d2c32c713d8dcae7c603407faa5f0fb810631670e
8fce8115d8a725afa92eb3910ded29d4c852e5133eba78a425054f41f7142603
O=S(=O)(Nc1cccc(OCCc2ccccc2)c1)c1ccccc1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6].[NH2;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[O;D1;H0:2]=[S;H0;D4;+0:1](=[O;D1;H0:3])(-[NH;D2;+0:7]-[c:8](:[c:9]):[c:10])-[c:4](:[c:5]):[c:6]
100
[{"value": 100.0, "product": "C(#N)C1=CC=C(C=C1)CCOC=1C=CC(=C(C1)NS(=O)(=O)C1=CC=CC=C1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 98.7, "product": "C(#N)C1=CC=C(C=C1)CCOC=1C=CC(=C(C1)NS(=O)(=O)C1=CC=CC=C1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
Benzenesulfonyl chloride (22 μL; 0.17 mmol) was added to a cold solution (ice:water temperature) of amino-5-[2-(4-cyanophenyl)ethoxy]-2-methylbenzene (0.041 g; 0.16 mmol; from step (ii) above) in pyridine (4 mL) The reaction flask was left overnight in a refrigerator. NaHCO3/aq (sat.) was added and the solution extract...
10.6084/m9.figshare.5104873.v1
null
Primary amine.Sulfonyl halide
Sulfonamide
null
null
c1ccccc1.c1ccccc1.c1ccccc1
HCl
N1=CC=CC=C1
null
8
Cc1ccc(OCCc2ccc(C#N)cc2)cc1N.O=S(=O)(Cl)c1ccccc1>N1=CC=CC=C1>Cc1ccc(OCCc2ccc(C#N)cc2)cc1NS(=O)(=O)c1ccccc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-1111fc7a8f8d49969750bc356e38cf41
Cc1cc(NC(=O)OC(C)(C)C)cc(OCCc2ccc(C#N)cc2)c1>>Cc1cc(N)cc(OCCc2ccc(C#N)cc2)c1
C(C)(C)(C)OC(=O)NC1=CC(=CC(=C1)C)OCCC1=CC=C(C=C1)C#N>>NC1=CC(=CC(=C1)C)OCCC1=CC=C(C=C1)C#N
CC(C)(C)OC(=O)[NH:5][c:4]1[cH:3][c:2]([CH3:1])[cH:19][c:7]([O:8][CH2:9][CH2:10][c:11]2[cH:12][cH:13][c:14]([C:15]#[N:16])[cH:17][cH:18]2)[cH:6]1>>[CH3:1][c:2]1[cH:3][c:4]([NH2:5])[cH:6][c:7]([O:8][CH2:9][CH2:10][c:11]2[cH:12][cH:13][c:14]([C:15]#[N:16])[cH:17][cH:18]2)[cH:19]1
Cc1cc(NC(=O)OC(C)(C)C)cc(OCCc2ccc(C#N)cc2)c1
Cc1cc(N)cc(OCCc2ccc(C#N)cc2)c1
null
null
C(Cl)Cl.FC(C(=O)O)(F)F
Reduction
Hydrogenolysis of amides/imides/carbamates
3c33dd2a2d355ee5ba0287367e209aa147a39aa00607f0c95fb2bf1ade45d014
c5b5dffe7dd8beebdc1baa8b5b05300a9f7079e65dcfd42ade6f8a77ff09537d
c1ccc(CCOc2ccccc2)cc1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
null
[]
null
null
null
null
t-Butyloxycarbonylamino-3-[2-(4-cyanophenyl)ethoxy]-5-methylbenzene (1.55 g; 4.4 mmol; from step (ii) above) was stirred in a mixture of trifluoroacetic acid (10 mL) and methylene chloride (10 mL) for 3 hours. The solvent was removed in vacuo. The residue was dissolved in EtOAc (50 mL), washed with Na2CO3/aq (sat.) and...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Primary amine
null
null
c1ccccc1.c1ccccc1
HO-
C(Cl)Cl.FC(C(=O)O)(F)F
null
null
Cc1cc(NC(=O)OC(C)(C)C)cc(OCCc2ccc(C#N)cc2)c1>C(Cl)Cl.FC(C(=O)O)(F)F>Cc1cc(N)cc(OCCc2ccc(C#N)cc2)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d2f2a62a9a7f4a4bbe47ffbd989c1976
Cc1cc(N)cc(OCCc2ccc(C#N)cc2)c1.O=S(=O)(Cl)c1ccccc1>>Cc1cc(NS(=O)(=O)c2ccccc2)cc(OCCc2ccc(C#N)cc2)c1
C(=O)(O)[O-].[Na+].NC1=CC(=CC(=C1)C)OCCC1=CC=C(C=C1)C#N.C1(=CC=CC=C1)S(=O)(=O)Cl>>C(#N)C1=CC=C(C=C1)CCOC=1C=C(C=C(C1)C)NS(=O)(=O)C1=CC=CC=C1
[CH3:1][c:2]1[cH:3][c:4]([NH2:5])[cH:15][c:16]([O:17][CH2:18][CH2:19][c:20]2[cH:21][cH:22][c:23]([C:24]#[N:25])[cH:26][cH:27]2)[cH:28]1.Cl[S:6](=[O:7])(=[O:8])[c:9]1[cH:10][cH:11][cH:12][cH:13][cH:14]1>>[CH3:1][c:2]1[cH:3][c:4]([NH:5][S:6](=[O:7])(=[O:8])[c:9]2[cH:10][cH:11][cH:12][cH:13][cH:14]2)[cH:15][c:16]([O:17][C...
Cc1cc(N)cc(OCCc2ccc(C#N)cc2)c1.O=S(=O)(Cl)c1ccccc1
Cc1cc(NS(=O)(=O)c2ccccc2)cc(OCCc2ccc(C#N)cc2)c1
null
null
N1=CC=CC=C1
Acylation
Sulfonamide synthesis (Schotten-Baumann) primary amine
4c44ef6d7646f6ef25dd125d2c32c713d8dcae7c603407faa5f0fb810631670e
8fce8115d8a725afa92eb3910ded29d4c852e5133eba78a425054f41f7142603
O=S(=O)(Nc1cccc(OCCc2ccccc2)c1)c1ccccc1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6].[NH2;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[O;D1;H0:2]=[S;H0;D4;+0:1](=[O;D1;H0:3])(-[NH;D2;+0:7]-[c:8](:[c:9]):[c:10])-[c:4](:[c:5]):[c:6]
97
[{"value": 97.0, "product": "C(#N)C1=CC=C(C=C1)CCOC=1C=C(C=C(C1)C)NS(=O)(=O)C1=CC=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 96.8, "product": "C(#N)C1=CC=C(C=C1)CCOC=1C=C(C=C(C1)C)NS(=O)(=O)C1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
To a cold solution (ice:water temperature) of amino-[3-2-(4-cyanophenyl)ethoxy]-5-methylbenzene (0.13 g; 0.50 mmol; from step (iii) above) in pyridine (5 mL) was added benzenesulfonyl chloride (71 μL; 0.55 mmol). After 2 hours stirring, NaHCO3/aq (sat.) was added, and the solution extracted with EtOAc. The combined org...
10.6084/m9.figshare.5104873.v1
null
Primary amine.Sulfonyl halide
Sulfonamide
null
null
c1ccccc1.c1ccccc1.c1ccccc1
HCl
N1=CC=CC=C1
null
2
Cc1cc(N)cc(OCCc2ccc(C#N)cc2)c1.O=S(=O)(Cl)c1ccccc1>N1=CC=CC=C1>Cc1cc(NS(=O)(=O)c2ccccc2)cc(OCCc2ccc(C#N)cc2)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-737deac25e6e41d4beb1f59e139c081e
Cc1ccc(S(=O)(=O)Cl)cc1.N#Cc1ccc(CCO)cc1>>Cc1ccc(S(=O)(=O)OCCc2ccc(C#N)cc2)cc1
C(#N)C1=CC=C(C=C1)CCO.C1(=CC=C(C=C1)S(=O)(=O)Cl)C.C(#N)C1=CC=C(C=C1)CCO>>C(#N)C1=CC=C(C=C1)CCOS(=O)(=O)C1=CC=C(C=C1)C
Cl[S:6]([c:5]1[cH:4][cH:3][c:2]([CH3:1])[cH:21][cH:20]1)(=[O:7])=[O:8].[OH:9][CH2:10][CH2:11][c:12]1[cH:13][cH:14][c:15]([C:16]#[N:17])[cH:18][cH:19]1>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([S:6](=[O:7])(=[O:8])[O:9][CH2:10][CH2:11][c:12]2[cH:13][cH:14][c:15]([C:16]#[N:17])[cH:18][cH:19]2)[cH:20][cH:21]1
Cc1ccc(S(=O)(=O)Cl)cc1.N#Cc1ccc(CCO)cc1
Cc1ccc(S(=O)(=O)OCCc2ccc(C#N)cc2)cc1
null
null
N1=CC=CC=C1
Acylation
Formation of Sulfonic Esters
d05d91207659f8fa672c205a316a670adfe2b92492fc9adad2ee3f241e574fb9
a7748b0f3b0eba3868d0cf03ae67721db046202accaaea9cadb4edbc96ec8768
O=S(=O)(OCCc1ccccc1)c1ccccc1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6].[C:7]-[C:8]-[OH;D1;+0:9]>>[C:7]-[C:8]-[O;H0;D2;+0:9]-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6]
67
[{"value": 66.0, "product": "C(#N)C1=CC=C(C=C1)CCOS(=O)(=O)C1=CC=C(C=C1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 67.0, "product": "C(#N)C1=CC=C(C=C1)CCOS(=O)(=O)C1=CC=C(C=C1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
2-(4-Cyanophenyl)ethanol (1.46 g; 9.9 mmol) and 4-toluenesulfonyl chloride (1.9 g; 10 mmol) were stirred in pyridine (20 mL) at 5° C. for 3 hours. Work-up was performed by removing the solvent, addition of 2M aqueous HCl and extraction with EtOAc. The organic phase was washed with aqueous citric acid, then passed throu...
10.6084/m9.figshare.5104873.v1
null
Tosylate.Primary alcohol.Sulfonyl halide
Tosylate
null
null
c1ccccc1.c1ccccc1
HCl
N1=CC=CC=C1
null
null
Cc1ccc(S(=O)(=O)Cl)cc1.N#Cc1ccc(CCO)cc1>N1=CC=CC=C1>Cc1ccc(S(=O)(=O)OCCc2ccc(C#N)cc2)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b6e637c151884c909ff6ec6502860177
Cc1ccc(S(=O)(=O)OCCc2ccc(C#N)cc2)cc1.Nc1cccc(S)c1>>N#Cc1ccc(CCSc2cccc(N)c2)cc1
NC=1C=C(C=CC1)S.C(#N)C1=CC=C(C=C1)CCOS(=O)(=O)C1=CC=C(C=C1)C.C(=O)([O-])[O-].[K+].[K+].CCOCC>>NC1=CC(=CC=C1)SCCC1=CC=C(C=C1)C#N
Cc1ccc(S(=O)(=O)O[CH2:8][CH2:7][c:6]2[cH:5][cH:4][c:3]([C:2]#[N:1])[cH:18][cH:17]2)cc1.[SH:9][c:10]1[cH:11][cH:12][cH:13][c:14]([NH2:15])[cH:16]1>>[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][CH2:8][S:9][c:10]2[cH:11][cH:12][cH:13][c:14]([NH2:15])[cH:16]2)[cH:17][cH:18]1
Cc1ccc(S(=O)(=O)OCCc2ccc(C#N)cc2)cc1.Nc1cccc(S)c1
N#Cc1ccc(CCSc2cccc(N)c2)cc1
null
null
C(Cl)Cl.CCO
Heteroatom Alkylation and Arylation
OtherReaction
fa9f9600581ef05dca04b54e63c21080ab3037c0f706082a272f2da0c08c4f32
8d10c46c4c89029273335615fb077055d8239c352e37ee1740069c99de11581b
c1ccc(CCSc2ccccc2)cc1
C-c1:c:c:c(-S(=O)(=O)-O-[CH2;D2;+0:1]-[C:2]-[c:3]):c:c:1.[SH;D1;+0:4]-[c:5](:[c:6]):[c:7]>>[c:6]:[c:5](-[S;H0;D2;+0:4]-[CH2;D2;+0:1]-[C:2]-[c:3]):[c:7]
49
[{"value": 49.0, "product": "NC1=CC(=CC=C1)SCCC1=CC=C(C=C1)C#N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 48.8, "product": "NC1=CC(=CC=C1)SCCC1=CC=C(C=C1)C#N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
3-Aminothiophenol (0.87 g; 7.0 mmol), 4-toluenesulfonic acid-2-(4-cyanophenyl)ethyl ester (2.0 g; 6.6 mmol; from step (i) above) and K2CO3 (1 g) were stirred in a mixture of EtOH (10 mL) and CH2Cl2 for 4 hours. Addition of ether, washing with brine and 2M aqueous NaOH, drying (MgSO4), evaporation of the solvent and fla...
10.6084/m9.figshare.5104873.v1
null
Tosylate.Aromatic thiol
Monosulfide
c1ccccc1
null
c1ccccc1.c1ccccc1
TsOH.HO-
C(Cl)Cl.CCO
null
null
Cc1ccc(S(=O)(=O)OCCc2ccc(C#N)cc2)cc1.Nc1cccc(S)c1>C(Cl)Cl.CCO>N#Cc1ccc(CCSc2cccc(N)c2)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-900bd1dae3d14db3a3e119f5d642c9f2
N#Cc1ccc(CCSc2cccc(N)c2)cc1.O=S(=O)(Cl)c1ccccc1>>N#Cc1ccc(CCSc2cccc(NS(=O)(=O)c3ccccc3)c2)cc1
C1(=CC=CC=C1)S(=O)(=O)Cl.NC1=CC(=CC=C1)SCCC1=CC=C(C=C1)C#N.Cl>>C(#N)C1=CC=C(C=C1)CCSC=1C=C(C=CC1)NS(=O)(=O)C1=CC=CC=C1
[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][CH2:8][S:9][c:10]2[cH:11][cH:12][cH:13][c:14]([NH2:15])[cH:25]2)[cH:26][cH:27]1.Cl[S:16](=[O:17])(=[O:18])[c:19]1[cH:20][cH:21][cH:22][cH:23][cH:24]1>>[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][CH2:8][S:9][c:10]2[cH:11][cH:12][cH:13][c:14]([NH:15][S:16](=[O:17])(=[O:18])[c:19]...
N#Cc1ccc(CCSc2cccc(N)c2)cc1.O=S(=O)(Cl)c1ccccc1
N#Cc1ccc(CCSc2cccc(NS(=O)(=O)c3ccccc3)c2)cc1
null
null
N1=CC=CC=C1.C(Cl)Cl
Miscellaneous
Sulfonamide synthesis (Schotten-Baumann) primary amine
a86b0632821e188c0a5dc5a5a2aac298ab3eccaee8a52ba46078c3d5975a290d
50f8fbf3d327483c3eeff8f6cbd4065e4c7600bb501fbe08958a5c79a0926428
O=S(=O)(Nc1cccc(SCCc2ccccc2)c1)c1ccccc1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6].[NH2;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[O;D1;H0:2]=[S;H0;D4;+0:1](=[O;D1;H0:3])(-[NH;D2;+0:7]-[c:8](:[c:9]):[c:10])-[c:4](:[c:5]):[c:6]
82.1
[{"value": 82.0, "product": "C(#N)C1=CC=C(C=C1)CCSC=1C=C(C=CC1)NS(=O)(=O)C1=CC=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 82.1, "product": "C(#N)C1=CC=C(C=C1)CCSC=1C=C(C=CC1)NS(=O)(=O)C1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
Benzenesulfonyl chloride (0.62 g; 3.5 mmol) was added to a cold solution (ice:water temperature) of amino-3-[2-(4-cyanophenyl)ethylthio]benzene (0.80 g; 3.15 mmol; from step (ii) above) in a mixture of pyridine (1 mL) and CH2Cl2 (20 mL) over 10 minutes. After 3 hours stirring, 2M aqueous HCl was added and the solution ...
10.6084/m9.figshare.5104873.v1
null
Primary amine.Sulfonyl halide
Sulfonamide
null
null
c1ccccc1.c1ccccc1.c1ccccc1
HCl
N1=CC=CC=C1.C(Cl)Cl
null
3
N#Cc1ccc(CCSc2cccc(N)c2)cc1.O=S(=O)(Cl)c1ccccc1>N1=CC=CC=C1.C(Cl)Cl>N#Cc1ccc(CCSc2cccc(NS(=O)(=O)c3ccccc3)c2)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-cca034ba033243bb8d279e449cf553e4
CCOC(=O)CNc1cc(C)cc(OCCc2ccc(C#N)cc2)c1.O=S(=O)(Cl)c1ccccc1Cl>>CCOC(=O)CN(c1cc(C)cc(OCCc2ccc(C#N)cc2)c1)S(=O)(=O)c1ccccc1Cl
C(=O)(O)[O-].[Na+].ClC1=C(C=CC=C1)S(=O)(=O)Cl.C(#N)C1=CC=C(C=C1)CCOC=1C=C(C=C(C1)C)NCC(=O)OCC.ClC1=C(C=CC=C1)S(=O)(=O)Cl>>ClC1=C(C=CC=C1)S(=O)(=O)N(C1=CC(=CC(=C1)C)OCCC1=CC=C(C=C1)C#N)CC(=O)OCC
[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH2:6][NH:7][c:8]1[cH:9][c:10]([CH3:11])[cH:12][c:13]([O:14][CH2:15][CH2:16][c:17]2[cH:18][cH:19][c:20]([C:21]#[N:22])[cH:23][cH:24]2)[cH:25]1.Cl[S:26](=[O:27])(=[O:28])[c:29]1[cH:30][cH:31][cH:32][cH:33][c:34]1[Cl:35]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH2:6][N:7]([c:8]1[cH:9][c:10]([CH...
CCOC(=O)CNc1cc(C)cc(OCCc2ccc(C#N)cc2)c1.O=S(=O)(Cl)c1ccccc1Cl
CCOC(=O)CN(c1cc(C)cc(OCCc2ccc(C#N)cc2)c1)S(=O)(=O)c1ccccc1Cl
null
null
N1=CC=CC=C1
Acylation
Sulfonamide synthesis (Schotten-Baumann) secondary amine
abeb6d9a0c70fe5baef0a8e555c2cd55ac2317f763ce7a0831775db7a04777d8
b7aca5a5d690b0846685a854bc946849e1041bfc3965161290b5ffb2821af09e
O=S(=O)(Nc1cccc(OCCc2ccccc2)c1)c1ccccc1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6].[C:7]-[#8:8]-[C:9](=[O;D1;H0:10])-[C:11]-[NH;D2;+0:12]-[c:13](:[c:14]):[c:15]>>[C:7]-[#8:8]-[C:9](=[O;D1;H0:10])-[C:11]-[N;H0;D3;+0:12](-[c:13](:[c:14]):[c:15])-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4](:[c:5]):[c:6]
62
[{"value": 62.0, "product": "ClC1=C(C=CC=C1)S(=O)(=O)N(C1=CC(=CC(=C1)C)OCCC1=CC=C(C=C1)C#N)CC(=O)OCC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 62.0, "product": "ClC1=C(C=CC=C1)S(=O)(=O)N(C1=CC(=CC(=C1)C)OCCC1=CC=C(C=C1)C#N)CC(=O)OCC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
2-Chlorobenzenesulfonyl chloride (0.225 g; 1.06 mmol) was added to a cold solution (ice:water temperature) of 3-[2-(4-cyanophenyl)ethoxy]-5-methylphenylaminoacetic acid, ethyl ester (0.30 g; 0.88 mmol; from step (i) above) in pyridine (10 mL). After 2 hours stirring the temperature was allowed to rise to ambient. After...
10.6084/m9.figshare.5104873.v1
null
Secondary amine.Sulfonyl halide
Tertiary amine
null
null
c1ccccc1.c1ccccc1.c1ccccc1
HCl
N1=CC=CC=C1
null
2
CCOC(=O)CNc1cc(C)cc(OCCc2ccc(C#N)cc2)c1.O=S(=O)(Cl)c1ccccc1Cl>N1=CC=CC=C1>CCOC(=O)CN(c1cc(C)cc(OCCc2ccc(C#N)cc2)c1)S(=O)(=O)c1ccccc1Cl
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d998d87bde2546cc85cd8edefb426c90
C=CC(=O)OCC.Cc1cc(N)cc(OCCc2ccc(C#N)cc2)c1>>CCOC(=O)C(C)Nc1cc(C)cc(OCCc2ccc(C#N)cc2)c1
NC1=CC(=CC(=C1)C)OCCC1=CC=C(C=C1)C#N.C(C=C)(=O)OCC.C(C)(=O)O>>C(#N)C1=CC=C(C=C1)CCOC=1C=C(C=C(C1)C)NC(C(=O)OCC)C
[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]=[CH2:7].[NH2:8][c:9]1[cH:10][c:11]([CH3:12])[cH:13][c:14]([O:15][CH2:16][CH2:17][c:18]2[cH:19][cH:20][c:21]([C:22]#[N:23])[cH:24][cH:25]2)[cH:26]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]([CH3:7])[NH:8][c:9]1[cH:10][c:11]([CH3:12])[cH:13][c:14]([O:15][CH2:16][CH2:17][c:18]2[cH:19][...
C=CC(=O)OCC.Cc1cc(N)cc(OCCc2ccc(C#N)cc2)c1
CCOC(=O)C(C)Nc1cc(C)cc(OCCc2ccc(C#N)cc2)c1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
1a11d98577799a07170cd5efd9dd7bb03f34d533a77a248c8322bf305dad4248
d462df48e06a3b2a50bc83cb7c56b836b8a054b4c300671faa54924b570d58bc
c1ccc(CCOc2ccccc2)cc1
[C:1]-[#8:2]-[C:3](=[O;D1;H0:4])-[CH;D2;+0:5]=[CH2;D1;+0:6].[NH2;D1;+0:7]-[c:8](:[c:9]):[c:10]>>[C:1]-[#8:2]-[C:3](=[O;D1;H0:4])-[CH;D3;+0:5](-[CH3;D1;+0:6])-[NH;D2;+0:7]-[c:8](:[c:9]):[c:10]
29
[{"value": 29.0, "product": "C(#N)C1=CC=C(C=C1)CCOC=1C=C(C=C(C1)C)NC(C(=O)OCC)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 28.9, "product": "C(#N)C1=CC=C(C=C1)CCOC=1C=C(C=C(C1)C)NC(C(=O)OCC)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Amino-3-[2-(4-cyanophenyl)ethoxy]-5-methylbenzene (0.252 g; 1.00 mmol; from Example 17(iii) above), ethyl acrylate (130 μL; 1.2 mmol) and acetic acid (9 μL; 0.15 mmol) were refluxed together for 8 hours. After evaporation in vacuo, the resultant black oil was purified by flash chromatography (SiO2; EtOAc:heptane (3:7))...
10.6084/m9.figshare.5104873.v1
null
Ester.Primary amine.Vinyl
Ester.Secondary amine
null
null
c1ccccc1.c1ccccc1
null
null
null
null
C=CC(=O)OCC.Cc1cc(N)cc(OCCc2ccc(C#N)cc2)c1>>CCOC(=O)C(C)Nc1cc(C)cc(OCCc2ccc(C#N)cc2)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e472ba652644422cb5d716850cd2c733
Cc1cc(N)cc(OCCc2ccc(C#N)cc2)c1.O=S(=O)(Cl)c1ccccc1Cl>>Cc1cc(OCCc2ccc(C#N)cc2)cc(-c2cccc(S(N)(=O)=O)c2Cl)c1
ClC1=C(C=CC=C1)S(=O)(=O)Cl.NC1=CC(=CC(=C1)C)OCCC1=CC=C(C=C1)C#N.N1=CC=CC=C1.O.CCOC(=O)C>>C(#N)C1=CC=C(C=C1)CCOC=1C=C(C=C(C1)C)C=1C(=C(C=CC1)S(=O)(=O)N)Cl
[CH3:1][c:2]1[cH:3][c:4]([O:5][CH2:6][CH2:7][c:8]2[cH:9][cH:10][c:11]([C:12]#[N:13])[cH:14][cH:15]2)[cH:16][c:17]([NH2:24])[cH:29]1.Cl[S:23]([c:22]1[cH:21][cH:20][cH:19][cH:18][c:27]1[Cl:28])(=[O:25])=[O:26]>>[CH3:1][c:2]1[cH:3][c:4]([O:5][CH2:6][CH2:7][c:8]2[cH:9][cH:10][c:11]([C:12]#[N:13])[cH:14][cH:15]2)[cH:16][c:1...
Cc1cc(N)cc(OCCc2ccc(C#N)cc2)c1.O=S(=O)(Cl)c1ccccc1Cl
Cc1cc(OCCc2ccc(C#N)cc2)cc(-c2cccc(S(N)(=O)=O)c2Cl)c1
null
null
null
Acylation
OtherReaction
9056a2ae05f3f48721e59db8b9dcb944d8d3e9953d69e7da0ce4e42b3cfd7c9e
8fce8115d8a725afa92eb3910ded29d4c852e5133eba78a425054f41f7142603
c1ccc(CCOc2cccc(-c3ccccc3)c2)cc1
Cl-[S;H0;D4;+0:1](=[O;D1;H0:2])(=[O;D1;H0:3])-[c:4]1:[c:5]:[c:6]:[c:7]:[cH;D2;+0:8]:[c:9]:1-[Cl;D1;H0:10].[NH2;D1;+0:11]-[c;H0;D3;+0:12](:[c:13]:[c:14]):[c:15]:[c:16]>>[Cl;D1;H0:10]-[c:9]1:[c:4](-[S;H0;D4;+0:1](-[NH2;D1;+0:11])(=[O;D1;H0:2])=[O;D1;H0:3]):[c:5]:[c:6]:[c:7]:[c;H0;D3;+0:8]:1-[c;H0;D3;+0:12](:[c:13]:[c:14]...
78
[{"value": 78.0, "product": "C(#N)C1=CC=C(C=C1)CCOC=1C=C(C=C(C1)C)C=1C(=C(C=CC1)S(=O)(=O)N)Cl", "details": "PERCENTYIELD", "is_desired": false}]
null
null
4
HOUR
2-Chlorophenylsulfonyl chloride (0.152 g; 0.72 mmol) was added to a cooled solution (ice:water temperature) of amino-3-[2-(4-cyanophenyl)ethoxy]-5-methylbenzene (0.16 g; 0.60 mmol; from Example 17(iii) above) in pyridine (5 mL), and the resultant orange solution was stirred for 4 hours. Addition of H2O (30 mL), extract...
10.6084/m9.figshare.5104873.v1
null
Primary amine.Sulfonyl halide
Sulfonamide
c1ccccc1.c1ccccc1
c1ccccc1.c1ccccc1
c1ccccc1.c1ccccc1.c1ccccc1
HCl
null
null
4
Cc1cc(N)cc(OCCc2ccc(C#N)cc2)c1.O=S(=O)(Cl)c1ccccc1Cl>>Cc1cc(OCCc2ccc(C#N)cc2)cc(-c2cccc(S(N)(=O)=O)c2Cl)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-8b5caf0ce965422b920c209aacc255dd
CCOC(=O)CBr.N#Cc1ccc(CCOc2cccc(NS(=O)(=O)c3ccccc3)c2)cc1>>CCOC(=O)CN(c1cccc(OCCc2ccc(C#N)cc2)c1)S(=O)(=O)c1ccccc1
C(#N)C1=CC=C(C=C1)CCOC=1C=C(C=CC1)NS(=O)(=O)C1=CC=CC=C1.C(=O)([O-])[O-].[K+].[K+].BrCC(=O)OCC>>C1(=CC=CC=C1)S(=O)(=O)N(C1=CC(=CC=C1)OCCC1=CC=C(C=C1)C#N)CC(=O)OCC
Br[CH2:6][C:4]([O:3][CH2:2][CH3:1])=[O:5].[NH:7]([c:8]1[cH:9][cH:10][cH:11][c:12]([O:13][CH2:14][CH2:15][c:16]2[cH:17][cH:18][c:19]([C:20]#[N:21])[cH:22][cH:23]2)[cH:24]1)[S:25](=[O:26])(=[O:27])[c:28]1[cH:29][cH:30][cH:31][cH:32][cH:33]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH2:6][N:7]([c:8]1[cH:9][cH:10][cH:11][c:12]([O...
CCOC(=O)CBr.N#Cc1ccc(CCOc2cccc(NS(=O)(=O)c3ccccc3)c2)cc1
CCOC(=O)CN(c1cccc(OCCc2ccc(C#N)cc2)c1)S(=O)(=O)c1ccccc1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
2f528facaf9aa1ab05620b510ae63e5e27715204b772ae8ea86d62f30b49e54b
dc829e3fdfa2d32260f0309a759a8629d6d95173de69dce05d7915b3a870e113
O=S(=O)(Nc1cccc(OCCc2ccccc2)c1)c1ccccc1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C:5].[O;D1;H0:6]=[#16:7](=[O;D1;H0:8])(-[c:9])-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]>>[C:5]-[#8:4]-[C:2](=[O;D1;H0:3])-[CH2;D2;+0:1]-[N;H0;D3;+0:10](-[c:11](:[c:12]):[c:13])-[#16:7](=[O;D1;H0:6])(=[O;D1;H0:8])-[c:9]
null
[]
null
null
null
null
N-{3-[2-(4-Cyanophenyl)ethoxy]phenyl}benzenesulfonamide (0.179 g; 0.47 mmol; from Example 1(iv) above), K2CO3 (0.082 g; 0.59 mmol) and ethyl bromoacetate (63 μL; 0.57 mmol) were stirred in DMF (10 mL) for 1 hour at room temperature, then 1 hour at 60° C. The mixture was filtered and the solvent removed in vacuo. The re...
10.6084/m9.figshare.5104873.v1
null
Sulfonamide.Primary halide
Ester.Tertiary amine
null
null
c1ccccc1.c1ccccc1.c1ccccc1
HBr
CN(C)C=O
null
null
CCOC(=O)CBr.N#Cc1ccc(CCOc2cccc(NS(=O)(=O)c3ccccc3)c2)cc1>CN(C)C=O>CCOC(=O)CN(c1cccc(OCCc2ccc(C#N)cc2)c1)S(=O)(=O)c1ccccc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a760ed3aa08d43f0a0a97f8b15340fd1
N#Cc1ccc(CCOc2cccc(NS(=O)(=O)c3ccccc3)c2)cc1.OCCCl>>N#Cc1ccc(CCOc2cccc(N(CCO)S(=O)(=O)c3ccccc3)c2)cc1
C(#N)C1=CC=C(C=C1)CCOC=1C=C(C=CC1)NS(=O)(=O)C1=CC=CC=C1.C(=O)([O-])[O-].[K+].[K+].ClCCO.[Na+].[I-]>>C(#N)C1=CC=C(C=C1)CCOC=1C=C(C=CC1)N(S(=O)(=O)C1=CC=CC=C1)CCO
[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][CH2:8][O:9][c:10]2[cH:11][cH:12][cH:13][c:14]([NH:15][S:19](=[O:20])(=[O:21])[c:22]3[cH:23][cH:24][cH:25][cH:26][cH:27]3)[cH:28]2)[cH:29][cH:30]1.Cl[CH2:16][CH2:17][OH:18]>>[N:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][CH2:8][O:9][c:10]2[cH:11][cH:12][cH:13][c:14]([N:15]([CH2:16]...
N#Cc1ccc(CCOc2cccc(NS(=O)(=O)c3ccccc3)c2)cc1.OCCCl
N#Cc1ccc(CCOc2cccc(N(CCO)S(=O)(=O)c3ccccc3)c2)cc1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
0fe6648877a29ae177a907a0d252f35d8beab440bf428116c5424a67bc0e72cd
0b054affe7e4bb904ceae512aabc19d89c93551cb46dfbc6f220fc85e5eeff75
O=S(=O)(Nc1cccc(OCCc2ccccc2)c1)c1ccccc1
Cl-[CH2;D2;+0:1]-[C:2]-[O;D1;H1:3].[O;D1;H0:4]=[#16:5](=[O;D1;H0:6])(-[c:7])-[NH;D2;+0:8]-[c:9](:[c:10]):[c:11]>>[O;D1;H0:4]=[#16:5](=[O;D1;H0:6])(-[c:7])-[N;H0;D3;+0:8](-[CH2;D2;+0:1]-[C:2]-[O;D1;H1:3])-[c:9](:[c:10]):[c:11]
45.2
[{"value": 45.0, "product": "C(#N)C1=CC=C(C=C1)CCOC=1C=C(C=CC1)N(S(=O)(=O)C1=CC=CC=C1)CCO", "details": "PERCENTYIELD", "is_desired": false}, {"value": 45.2, "product": "C(#N)C1=CC=C(C=C1)CCOC=1C=C(C=CC1)N(S(=O)(=O)C1=CC=CC=C1)CCO", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
N-{3-[2-(4-cyanophenyl)ethoxy]phenyl}benzenesulfonamide (0.093 g; 0.246 mmol; from Example 1(iv) above), K2CO3 (0.047 g, 0.34 mmol), 2-chloroethanol (0.028 g; 0.34 mmol) and NaI (0.052 g; 0.34 mmol) were stirred in DMF (4 mL) for 24 hours at 100° C. The solvent was removed in vacuo. The residue was dissolved in water a...
10.6084/m9.figshare.5104873.v1
null
Sulfonamide.Primary halide
Tertiary amine
null
null
c1ccccc1.c1ccccc1.c1ccccc1
HCl
CN(C)C=O
null
null
N#Cc1ccc(CCOc2cccc(NS(=O)(=O)c3ccccc3)c2)cc1.OCCCl>CN(C)C=O>N#Cc1ccc(CCOc2cccc(N(CCO)S(=O)(=O)c3ccccc3)c2)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-715ae417cb214b94910b6d81fbe9317b
CC(C)(N(c1cccc(OCCc2ccc(C#N)cc2)c1)S(=O)(=O)c1ccccc1)P(=O)=O.NO>>CC(C)(N(c1cccc(OCCc2ccc(N)cc2C=NO)c1)S(=O)(=O)c1ccccc1)P(=O)=O
Cl.NO.C(C)N(CC)CC.C(#N)C1=CC=C(C=C1)CCOC=1C=C(C=CC1)N(S(=O)(=O)C1=CC=CC=C1)C(P(=O)=O)(C)C.CCO>>NC1=CC(=C(C=C1)CCOC=1C=C(C=CC1)N(S(=O)(=O)C1=CC=CC=C1)C(P(=O)=O)(C)C)C=NO
[CH3:1][C:2]([CH3:3])([N:4]([c:5]1[cH:6][cH:7][cH:8][c:9]([O:10][CH2:11][CH2:12][c:13]2[cH:14][cH:15][c:16]([C:20]#[N:17])[cH:18][cH:19]2)[cH:23]1)[S:24](=[O:25])(=[O:26])[c:27]1[cH:28][cH:29][cH:30][cH:31][cH:32]1)[P:33](=[O:34])=[O:35].[NH2:21][OH:22]>>[CH3:1][C:2]([CH3:3])([N:4]([c:5]1[cH:6][cH:7][cH:8][c:9]([O:10][...
CC(C)(N(c1cccc(OCCc2ccc(C#N)cc2)c1)S(=O)(=O)c1ccccc1)P(=O)=O.NO
CC(C)(N(c1cccc(OCCc2ccc(N)cc2C=NO)c1)S(=O)(=O)c1ccccc1)P(=O)=O
null
null
null
Functional Group Interconversion
OtherReaction
9a4199cbda10cf607df9505ac5108b87c80aa46a5446ba42a75d811e5b06fd6e
5faaa3b624f22840cc937b2c79d5ab2d184e066c323862d533df1ecb9df1680d
O=S(=O)(Nc1cccc(OCCc2ccccc2)c1)c1ccccc1
[C:1]-[c:2]1:[c:3]:[c:4]:[c;H0;D3;+0:5](-[C;H0;D2;+0:6]#[N;H0;D1;+0:7]):[c:8]:[cH;D2;+0:9]:1.[NH2;D1;+0:10]-[O;D1;H1:11]>>[C:1]-[c:2]1:[c:3]:[c:4]:[c;H0;D3;+0:5](-[NH2;D1;+0:7]):[c:8]:[c;H0;D3;+0:9]:1-[CH;D2;+0:6]=[N;H0;D2;+0:10]-[O;D1;H1:11]
56
[{"value": 56.0, "product": "NC1=CC(=C(C=C1)CCOC=1C=C(C=CC1)N(S(=O)(=O)C1=CC=CC=C1)C(P(=O)=O)(C)C)C=NO", "details": "PERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
Hydroxylamine hydrochloride (0.018 g; 0.26 mmol) and triethylamine (45 μL, 0.33 mmol) were added to a solution of N-{3-[2-(4-cyanophenyl)ethoxy]phenyl}-N-(dimethyloxophosphinylmethyl)-benzenesulfonamide (0.090 g; 0.192 mmol; from step (i) above) in EtOH (6 mL). The mixture was heated at reflux for 3 hours, stirred at r...
10.6084/m9.figshare.5104873.v1
null
Nitrile.Primary amine
Primary amine.Oxime
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1.c1ccccc1
null
null
null
8
CC(C)(N(c1cccc(OCCc2ccc(C#N)cc2)c1)S(=O)(=O)c1ccccc1)P(=O)=O.NO>>CC(C)(N(c1cccc(OCCc2ccc(N)cc2C=NO)c1)S(=O)(=O)c1ccccc1)P(=O)=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-328c4fe48c48430ea2808ad405c1e724
Cc1cc(O)cc(O)c1.N#Cc1ccc(CCO)cc1>>Cc1cc(O)cc(OCCc2ccc(C#N)cc2)c1
CCOC(=O)/N=N/C(=O)OCC.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.OC=1C=C(C=C(C1)O)C.C(#N)C1=CC=C(C=C1)CCO>>C(#N)C1=CC=C(C=C1)CCOC=1C=C(C=C(C1)C)O
O[c:7]1[cH:6][c:4]([OH:5])[cH:3][c:2]([CH3:1])[cH:19]1.[OH:8][CH2:9][CH2:10][c:11]1[cH:12][cH:13][c:14]([C:15]#[N:16])[cH:17][cH:18]1>>[CH3:1][c:2]1[cH:3][c:4]([OH:5])[cH:6][c:7]([O:8][CH2:9][CH2:10][c:11]2[cH:12][cH:13][c:14]([C:15]#[N:16])[cH:17][cH:18]2)[cH:19]1
Cc1cc(O)cc(O)c1.N#Cc1ccc(CCO)cc1
Cc1cc(O)cc(OCCc2ccc(C#N)cc2)c1
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
8915084acbaaf997bf0f89ff5187cb2f89c25dc683fffc57b3391298c8430dd9
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1ccc(CCOc2ccccc2)cc1
O-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[C:6]-[C:7]-[OH;D1;+0:8]>>[C:6]-[C:7]-[O;H0;D2;+0:8]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5]
37
[{"value": 37.0, "product": "C(#N)C1=CC=C(C=C1)CCOC=1C=C(C=C(C1)C)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 36.5, "product": "C(#N)C1=CC=C(C=C1)CCOC=1C=C(C=C(C1)C)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
Triphenylphoshine (7.86 g; 30 mmol), 3,5-dihydroxytoluene (2.5 g; 20 mmol) and 2-(4-cyanophenyl)ethanol (4.41 g; 30 mmol) were dissolved in THF (50 mL). Diethylazodicarboxylate (5.22 g; 30 mmol; dissolved in THF (10 mL)), was added and the solution was stirred at room temperature overnight. The solvent was removed in v...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HO-
C1CCOC1
null
8
Cc1cc(O)cc(O)c1.N#Cc1ccc(CCO)cc1>C1CCOC1>Cc1cc(O)cc(OCCc2ccc(C#N)cc2)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b4f023441e99406caabd808a847bd821
COc1cc(Cl)cc(OC)c1>>Oc1cc(O)cc(Cl)c1
B(Br)(Br)Br.ClC1=CC(=CC(=C1)OC)OC>>ClC1=CC(=CC(=C1)O)O
C[O:1][c:2]1[cH:3][c:4]([O:5]C)[cH:6][c:7]([Cl:8])[cH:9]1>>[OH:1][c:2]1[cH:3][c:4]([OH:5])[cH:6][c:7]([Cl:8])[cH:9]1
COc1cc(Cl)cc(OC)c1
Oc1cc(O)cc(Cl)c1
null
null
C(Cl)Cl
Deprotection
OtherReaction
a0f05885bbc65ae2846cad0ac34029941211b2ef3a426958b0c8aa83bb16fe86
9df751cd682ad9d54ed75d7313aaead6a019c5d37ede15c4672866d319b900ff
c1ccccc1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]:[c:5](-[O;H0;D2;+0:6]-C):[c:7]>>[OH;D1;+0:1]-[c:2](:[c:3]):[c:4]:[c:5](-[OH;D1;+0:6]):[c:7]
207.5
[{"value": 100.0, "product": "ClC1=CC(=CC(=C1)O)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 207.5, "product": "ClC1=CC(=CC(=C1)O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
4
DAY
BBr3 (26 mL; 0.275 mmol) was added to a solution of chloro-3,5-dimethyoxybenzene (10 g; 30 mmol) in CH2Cl2 (100 mL) at −70° C. The cooling bath was removed and the solution was stirred at room temperature for 4 days. After re-cooling to −70° C., MeOH was added (150 mL). After evaporation of the solvent, toluene was add...
10.6084/m9.figshare.5104873.v1
null
Ether.Ether
Aromatic alcohol.Aromatic alcohol
null
null
c1ccccc1
Other
C(Cl)Cl
null
96
COc1cc(Cl)cc(OC)c1>C(Cl)Cl>Oc1cc(O)cc(Cl)c1