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-764201f239bd4d3e97dad5d5a4b1d001
CCNCC.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CO1>>CCN(CC)CC(O)COc1cc2ncnc(Oc3ccc4[nH]c(C)cc4c3)c2cc1OC
O1C(COC2=C(C=C3C(=NC=NC3=C2)OC=2C=C3C=C(NC3=CC2)C)OC)C1.C(C)NCC>>C(C)N(CC)CC(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[CH: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][CH:7]([OH:8])[CH2:9][O:10][c:11]1[cH:12][c:...
CCNCC.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CO1
CCN(CC)CC(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
[C;D1;H3:1]-[C:2]-[NH;D2;+0:3]-[C:4]-[C;D1;H3:5].[C:6]-[C:7]1-[CH2;D2;+0:8]-[O;H0;D2;+0:9]-1>>[C:6]-[C:7](-[OH;D1;+0:9])-[CH2;D2;+0:8]-[N;H0;D3;+0:3](-[C:2]-[C;D1;H3:1])-[C:4]-[C;D1;H3:5]
46
[{"value": 46.0, "product": "C(C)N(CC)CC(COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 45.2, "product": "C(C)N(CC)CC(COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
70
CELSIUS
null
null
A mixture of 7-(2,3-epoxypropoxy)-6-methoxy-4-(2-methylindol-5-yloxy) quinazoline (100 mg, 0.27 mmol), (prepared as described for the starting material in Example 162), and diethylamine (100 ul, 0.8 mmol) in DMF (4 ml) was heated at 70° C. for 24 hours. The solvent was removed by evaporation and the residue was purifie...
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
null
CCNCC.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CO1>CN(C)C=O>CCN(CC)CC(O)COc1cc2ncnc(Oc3ccc4[nH]c(C)cc4c3)c2cc1OC
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-df2ac05840054c5486acbdaca480a418
CN1CCNCC1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CO1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC(O)CN1CCN(C)CC1
O1C(COC2=C(C=C3C(=NC=NC3=C2)OC=2C=C3C=C(NC3=CC2)C)OC)C1.CN1CCNCC1>>OC(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][CH:26]1[O:27][CH2:28]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH...
CN1CCNCC1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CO1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC(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.[C:7]-[C:8]1-[CH2;D2;+0:9]-[O;H0;D2;+0:10]-1>>[C:7]-[C:8](-[OH;D1;+0:10])-[CH2;D2;+0:9]-[N;H0;D3;+0:4]1-[C:3]-[C:2]-[#7:1]-[C:6]-[C:5]-1
32
[{"value": 32.0, "product": "OC(COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)CN1CCN(CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 31.8, "product": "OC(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
null
null
A mixture of 7-(2,3-epoxypropoxy)-6-methoxy-4-(2-methylindol-5-yloxy) quinazoline (100 mg, 0.27 mmol), (prepared as described for the starting material in Example 162), and N-methylpiperazine (200 ul, 1.8 mmol) in DMF (4 ml) was heated at 70° C. for 24 hours. The solvent was removed by evaporation and the residue was r...
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
null
CN1CCNCC1.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CO1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC(O)CN1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-7c1252df20534aecbea6a4ad46e7aa95
CC(C)N.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CO1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC(O)CNC(C)C
O1C(COC2=C(C=C3C(=NC=NC3=C2)OC=2C=C3C=C(NC3=CC2)C)OC)C1.C(C)(C)N>>OC(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][CH:26]1[O:27][CH2:28]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[cH:...
CC(C)N.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CO1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC(O)CNC(C)C
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
f75f8fec78b0ee9c8e880101c8c57c2a3edaac070bc7ad0163a34826e2af8c65
04c78336d85647f6dca3040f384f77009d1b541aac7f8ccf33aa9798091ceab8
c1ccc2c(Oc3ccc4[nH]ccc4c3)ncnc2c1
[C;D1;H3:1]-[C:2](-[C;D1;H3:3])-[NH2;D1;+0:4].[C:5]-[C:6]1-[CH2;D2;+0:7]-[O;H0;D2;+0:8]-1>>[C:5]-[C:6](-[OH;D1;+0:8])-[CH2;D2;+0:7]-[NH;D2;+0:4]-[C:2](-[C;D1;H3:1])-[C;D1;H3:3]
16
[{"value": 16.0, "product": "OC(COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)CNC(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 15.3, "product": "OC(COC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=C(NC2=CC1)C)OC)CNC(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
70
CELSIUS
null
null
A mixture of 7-(2,3-epoxypropoxy)-6-methoxy-4-(2-methylindol-5-yloxy) quinazoline (100 mg, 0.27 mmol), (prepared as described for the starting material in Example 162), and isopropylamine (100 ul, 0.8 mmol) in DMF (4 ml) was heated at 70° C. for 24 hours. The solvent was removed by evaporation and the residue was purif...
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
70
null
CC(C)N.COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CO1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC(O)CNC(C)C
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-9ffd160700234287a5acf4978eea8324
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1cc2cc[nH]c2cc1C(F)(F)F>>COc1cc2c(Oc3cc4cc[nH]c4cc3C(F)(F)F)ncnc2cc1OCCCN1CCCCC1
CC(=O)N(C)C.ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1.C([O-])([O-])=O.[K+].[K+].OC=1C=C2C=CNC2=CC1C(F)(F)F>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCCC1)OC=1C=C2C=CNC2=CC1C(F)(F)F
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:26]([O:27][CH2:28][CH2:29][CH2:30][N:31]3[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]3)[cH:25][c:24]2[n:23][cH:22][n:21]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[C:17]([F:18])([F:19])[F:20]>>[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...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1cc2cc[nH]c2cc1C(F)(F)F
COc1cc2c(Oc3cc4cc[nH]c4cc3C(F)(F)F)ncnc2cc1OCCCN1CCCCC1
null
null
ClCCl
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]
25
[{"value": 25.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCCC1)OC=1C=C2C=CNC2=CC1C(F)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 24.8, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCCC1)OC=1C=C2C=CNC2=CC1C(F)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
95
CELSIUS
1.5
HOUR
A mixture of 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (168 mg, 0.5 mmol), (prepared as described for the starting material in Example 67), potassium carbonate (276 mg, 2.0 mmol) and 5-hydroxy-6-trifluoromethylindole (110 mg, 0.55 mmol) and DMA (4.0 ml) were stirred at 95° C. for 1.5 hours and allowed to co...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
ClCCl
95
1.5
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1cc2cc[nH]c2cc1C(F)(F)F>ClCCl>COc1cc2c(Oc3cc4cc[nH]c4cc3C(F)(F)F)ncnc2cc1OCCCN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-12783713139945e38ae19dee0a14a42e
O=[N+]([O-])c1ccc(Cl)c(C(F)(F)F)c1.OCc1ccccc1>>O=[N+]([O-])c1ccc(OCc2ccccc2)c(C(F)(F)F)c1
C(C)(=O)O.[H-].[Na+].C(C1=CC=CC=C1)O.ClC1=C(C=C(C=C1)[N+](=O)[O-])C(F)(F)F>>C(C1=CC=CC=C1)OC1=C(C=C(C=C1)[N+](=O)[O-])C(F)(F)F
Cl[c:7]1[cH:6][cH:5][c:4]([N+:2](=[O:1])[O-:3])[cH:21][c:16]1[C:17]([F:18])([F:19])[F:20].[OH:8][CH2:9][c:10]1[cH:11][cH:12][cH:13][cH:14][cH:15]1>>[O:1]=[N+:2]([O-:3])[c:4]1[cH:5][cH:6][c:7]([O:8][CH2:9][c:10]2[cH:11][cH:12][cH:13][cH:14][cH:15]2)[c:16]([C:17]([F:18])([F:19])[F:20])[cH:21]1
O=[N+]([O-])c1ccc(Cl)c(C(F)(F)F)c1.OCc1ccccc1
O=[N+]([O-])c1ccc(OCc2ccccc2)c(C(F)(F)F)c1
null
null
ClCCl.CC(=O)N(C)C
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
4821d6d7238522ee9ef4538c00647e855becf4de3d9c939c0cec2b01c1e5e915
a4cafa7bcd156e21cca6eaac1b32e28ec8540642a31181122e6957f3d7559631
c1ccc(COc2ccccc2)cc1
Cl-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4](-[C:5](-[F;D1;H0:6])(-[F;D1;H0:7])-[F;D1;H0:8]):[c:9].[OH;D1;+0:10]-[C:11]-[c:12]>>[F;D1;H0:6]-[C:5](-[F;D1;H0:7])(-[F;D1;H0:8])-[c:4](:[c:9]):[c;H0;D3;+0:1](-[O;H0;D2;+0:10]-[C:11]-[c:12]):[c:2]:[c:3]
49
[{"value": 49.0, "product": "C(C1=CC=CC=C1)OC1=C(C=C(C=C1)[N+](=O)[O-])C(F)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 44.4, "product": "C(C1=CC=CC=C1)OC1=C(C=C(C=C1)[N+](=O)[O-])C(F)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Sodium hydride (1.8 g, of a 60% dispersion in oil, 45 mmol) was added in portions to a stirred solution of benzyl alcohol (10.8 g, 100 mmol) in DMA (100 ml) with vigorous stirring under an atmosphere of nitrogen at ambient temperature. After warming to 45° C. for 30 minutes the mixture was cooled to ambient temperature...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary alcohol
Ether
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HCl
ClCCl.CC(=O)N(C)C
null
null
O=[N+]([O-])c1ccc(Cl)c(C(F)(F)F)c1.OCc1ccccc1>ClCCl.CC(=O)N(C)C>O=[N+]([O-])c1ccc(OCc2ccccc2)c(C(F)(F)F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3fc3145e35b4460c87d0579c588585ed
N#CCc1ccc(Cl)cc1.O=[N+]([O-])c1ccc(OCc2ccccc2)c(C(F)(F)F)c1>>N#CCc1cc(OCc2ccccc2)c(C(F)(F)F)cc1[N+](=O)[O-]
Cl.C(C1=CC=CC=C1)OC1=C(C=C(C=C1)[N+](=O)[O-])C(F)(F)F.ClC1=CC=C(C=C1)CC#N.CC(C)([O-])C.[K+]>>C(C1=CC=CC=C1)OC=1C(=CC(=C(C1)CC#N)[N+](=O)[O-])C(F)(F)F
Clc1cc[c:4]([CH2:3][C:2]#[N:1])[cH:5]c1.c1c[c:21]([N+:22](=[O:23])[O-:24])[cH:20][c:15]([C:16]([F:17])([F:18])[F:19])[c:6]1[O:7][CH2:8][c:9]1[cH:10][cH:11][cH:12][cH:13][cH:14]1>>[N:1]#[C:2][CH2:3][c:4]1[cH:5][c:6]([O:7][CH2:8][c:9]2[cH:10][cH:11][cH:12][cH:13][cH:14]2)[c:15]([C:16]([F:17])([F:18])[F:19])[cH:20][c:21]1...
N#CCc1ccc(Cl)cc1.O=[N+]([O-])c1ccc(OCc2ccccc2)c(C(F)(F)F)c1
N#CCc1cc(OCc2ccccc2)c(C(F)(F)F)cc1[N+](=O)[O-]
null
null
CN(C)C=O
Miscellaneous
OtherReaction
e1a86e32d8a62056777b80c3d8e217471ab53bfaa0552fe67a867bfc2dce42db
90896f03fa7176670c6618dd1123693033ce2a8538f8fd8da8706c8a6043dc98
c1ccc(COc2ccccc2)cc1
Cl-c1:c:[cH;D2;+0:1]:[c;H0;D3;+0:2](-[C:3]-[C:4]#[N;D1;H0:5]):c:c:1.[C:6]-[#8:7]-[c;H0;D3;+0:8]1:c:c:[c;H0;D3;+0:9](-[#7;+:10](-[O;-;D1;H0:11])=[O;D1;H0:12]):[c:13]:[c:14]:1-[C:15](-[F;D1;H0:16])(-[F;D1;H0:17])-[F;D1;H0:18]>>[C:6]-[#8:7]-[c;H0;D3;+0:8]1:[cH;D2;+0:1]:[c;H0;D3;+0:2](-[C:3]-[C:4]#[N;D1;H0:5]):[c;H0;D3;+0:...
96
[{"value": 77.0, "product": "C(C1=CC=CC=C1)OC=1C(=CC(=C(C1)CC#N)[N+](=O)[O-])C(F)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 96.0, "product": "C(C1=CC=CC=C1)OC=1C(=CC(=C(C1)CC#N)[N+](=O)[O-])C(F)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
-10
CELSIUS
1
HOUR
Potassium tert-butoxide (3.94 g, 35.4 mmol) was dissolved in anhydrous DMF (15 ml) and a mixture of 2-benzyloxy-5-nitro-trifluoromethylbenzene (3.5 g, 16.1 mmol) and 4-chlorophenylacetonitrile (2.96 g, 17.7 mmol) in DMF (20 ml) was added over 30 minutes keeping the temperature at −15C. The mixture was stirred at −10° C...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Ether.Nitro group
Ether.Nitro group
c1ccccc1.c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HCl
CN(C)C=O
-10
1
N#CCc1ccc(Cl)cc1.O=[N+]([O-])c1ccc(OCc2ccccc2)c(C(F)(F)F)c1>CN(C)C=O>N#CCc1cc(OCc2ccccc2)c(C(F)(F)F)cc1[N+](=O)[O-]
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-6840e0bf182b4e299ed28de5d2ff9819
N#CCc1cc(OCc2ccccc2)c(C(F)(F)F)cc1[N+](=O)[O-]>>Oc1cc2cc[nH]c2cc1C(F)(F)F
O.C(C)(=O)O.C(C1=CC=CC=C1)OC=1C(=CC(=C(C1)CC#N)[N+](=O)[O-])C(F)(F)F>>OC=1C=C2C=CNC2=CC1C(F)(F)F
N#[C:6][CH2:5][c:4]1[cH:3][c:2]([O:1]Cc2ccccc2)[c:10]([C:11]([F:12])([F:13])[F:14])[cH:9][c:8]1[N+:7](=O)[O-]>>[OH:1][c:2]1[cH:3][c:4]2[cH:5][cH:6][nH:7][c:8]2[cH:9][c:10]1[C:11]([F:12])([F:13])[F:14]
N#CCc1cc(OCc2ccccc2)c(C(F)(F)F)cc1[N+](=O)[O-]
Oc1cc2cc[nH]c2cc1C(F)(F)F
null
[Pd]
C(C)O
Functional Group Interconversion
OtherReaction
d674d6fdb3b5cbb7247a702f066088407269945f41d65ac05ee14f7e0733fdaa
c2e261676da3d876901f8094899a33724e27f2712d56041d0a451c2699036a45
c1ccc2[nH]ccc2c1
N#[C;H0;D2;+0:1]-[CH2;D2;+0:2]-[c:3]1:[c:4]:[c:5](-[O;H0;D2;+0:6]-C-c2:c:c:c:c:c:2):[c:7]:[c:8]:[c:9]:1-[N+;H0;D3:10](=O)-[O-]>>[OH;D1;+0:6]-[c:5]1:[c:7]:[c:8]:[c:9]2:[nH;D2;+0:10]:[cH;D2;+0:1]:[cH;D2;+0:2]:[c:3]:2:[c:4]:1
84.4
[{"value": 84.0, "product": "OC=1C=C2C=CNC2=CC1C(F)(F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 84.4, "product": "OC=1C=C2C=CNC2=CC1C(F)(F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
5-Benzyloxy-2-nitro-4(trifluoromethyl)phenylacetonitrile (2.22 g, 6.6 mmol) was dissolved in ethanol (45 ml), water (5 ml) and acetic acid (0.32 ml) then hydrogenated with 10% palladium on carbon at 1 atmosphere pressure for 2 hours. The catalyst was filtered off and filtrate evaporated to give 5-hydroxy-6-trifluoromet...
10.6084/m9.figshare.5104873.v1
null
Ether.Nitrile.Nitro group
Aromatic alcohol
c1ccccc1.c1ccccc1
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1
HO-
[Pd].C(C)O
null
null
N#CCc1cc(OCc2ccccc2)c(C(F)(F)F)cc1[N+](=O)[O-]>[Pd].C(C)O>Oc1cc2cc[nH]c2cc1C(F)(F)F
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-1a37df9bbfcc43518a54b12f8978e98f
COc1cc2[nH]ccc2cc1O.COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1>>COc1cc2c(Oc3cc4cc[nH]c4cc3OC)ncnc2cc1OCCCN1CCCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1.C([O-])([O-])=O.[K+].[K+].OC=1C=C2C=CNC2=CC1OC>>COC1=C(C=C2C=CNC2=C1)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1
[OH:7][c:8]1[cH:9][c:10]2[cH:11][cH:12][nH:13][c:14]2[cH:15][c:16]1[O:17][CH3:18].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>>[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...
COc1cc2[nH]ccc2cc1O.COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1
COc1cc2c(Oc3cc4cc[nH]c4cc3OC)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]
38.2
[{"value": 38.0, "product": "COC1=C(C=C2C=CNC2=C1)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 38.2, "product": "COC1=C(C=C2C=CNC2=C1)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
95
CELSIUS
2.5
HOUR
A mixture of 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (200 mg, 0.6 mmol), (prepared as described for the starting material in Example 67), potassium carbonate (248 mg, 1.8 mmol) and 5-hydroxy-6-methoxyindole (127 mg, 0.78 mmol) in DMA (4.0 ml) was stirred at 95° C. for 2.5 hours. The reaction mixture was a...
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
95
2.5
COc1cc2[nH]ccc2cc1O.COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1>CC(=O)N(C)C>COc1cc2c(Oc3cc4cc[nH]c4cc3OC)ncnc2cc1OCCCN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-6c40b817a99245b5ae1c0af10020a5d8
COc1cc2[nH]ccc2cc1OCc1ccccc1>>COc1cc2[nH]ccc2cc1O
C(C1=CC=CC=C1)OC=1C=C2C=CNC2=CC1OC>>OC=1C=C2C=CNC2=CC1OC
c1ccc(C[O:12][c:11]2[c:3]([O:2][CH3:1])[cH:4][c:5]3[nH:6][cH:7][cH:8][c:9]3[cH:10]2)cc1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[nH:6][cH:7][cH:8][c:9]2[cH:10][c:11]1[OH:12]
COc1cc2[nH]ccc2cc1OCc1ccccc1
COc1cc2[nH]ccc2cc1O
null
[Pd]
CO
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]
87
[{"value": 87.0, "product": "OC=1C=C2C=CNC2=CC1OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 7.9, "product": "OC=1C=C2C=CNC2=CC1OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
5-Benzyloxy-6-methoxyindole (253 mg, 11.0 mmol) was hydrogenated at 1 atmosphere pressure in methanol (10 ml) with 10% palladium on carbon (50 mg) for 2 hours at 25° C. The catalyst was filtered off and the filtrate evaporated to give 5-hydroxy-6-methoxylindole (141 mg, 87%). Conditions: See reaction.notes.procedure_de...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
c1ccccc1
null
c1ccc2[nH]ccc2c1
Other
[Pd].CO
null
null
COc1cc2[nH]ccc2cc1OCc1ccccc1>[Pd].CO>COc1cc2[nH]ccc2cc1O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-c9267b799df84f46929e357a34a8a5a4
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1cccc2[nH]ccc12>>COc1cc2c(Oc3cc4ccccc4[nH]3)ncnc2cc1OCCCN1CCCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1.C([O-])([O-])=O.[K+].[K+].OC1=C2C=CNC2=CC=C1>>N1C(=CC2=CC=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:22]([O:23][CH2:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]3)[cH:21][c:20]2[n:19][cH:18][n:17]1.[OH:7][c:11]1[c:10]2[cH:9][cH:8][nH:16][c:15]2[cH:14][cH:13][cH:12]1>>[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][cH:13][cH:14][c...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1cccc2[nH]ccc12
COc1cc2c(Oc3cc4ccccc4[nH]3)ncnc2cc1OCCCN1CCCCC1
null
null
CC(=O)N(C)C
Heteroatom Alkylation and Arylation
OtherReaction
5af8f53eb6fe20519bb1cf399cab4d8844ca0e30f8f4c67b935a221e33f2c4d3
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1ccc2[nH]c(Oc3ncnc4cc(OCCCN5CCCCC5)ccc34)cc2c1
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;H0;D3;+0:10]1:[c:11]:[c:12]:[c:13]:[c:14]2:[#7;a:15]:[cH;D2;+0:16]:[c:17]:[c:18]:2:1>>[c:6]:[c:5]1:[#7;a:4]:[c:3]:[#7;a:2]:[c;H0;D3;+0:1](-[O;H0;D2;+0:9]-[c;H0;D3;+0:16]2:[#7;a:15]:[c:14]3:[c:13]:[c:12]:[c:11]:[cH;D2;+0:10]:[c:18]:3:...
51
[{"value": 51.0, "product": "N1C(=CC2=CC=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 50.9, "product": "N1C(=CC2=CC=CC=C12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
85
CELSIUS
3
HOUR
A mixture of 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (200 mg, 0.595 mmol), (prepared as described for the starting material in Example 67), potassium carbonate (411 mg, 2.98 mmol) and 4-hydroxyindole (103 mg, 0.774 mmol) in DMA (2.0 ml) was stirred at 85° C. for 3 hours and allowed to cool to ambient temp...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1.c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
CC(=O)N(C)C
85
3
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1cccc2[nH]ccc12>CC(=O)N(C)C>COc1cc2c(Oc3cc4ccccc4[nH]3)ncnc2cc1OCCCN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-2ed001413ff043fca1378b9ad403d778
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1ccc2[nH]c3ccccc3c2c1>>COc1cc2c(Oc3ccc4[nH]c5ccccc5c4c3)ncnc2cc1OCCCN1CCCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1.C([O-])([O-])=O.[K+].[K+].OC=1C=CC=2NC3=CC=CC=C3C2C1>>C1=CC(=CC=2C3=CC=CC=C3NC12)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:26]([O:27][CH2:28][CH2:29][CH2:30][N:31]3[CH2:32][CH2:33][CH2:34][CH2:35][CH2:36]3)[cH:25][c:24]2[n:23][cH:22][n:21]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][c:13]3[cH:14][cH:15][cH:16][cH:17][c:18]3[c:19]2[cH:20]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1ccc2[nH]c3ccccc3c2c1
COc1cc2c(Oc3ccc4[nH]c5ccccc5c4c3)ncnc2cc1OCCCN1CCCCC1
null
null
CC(=O)N(C)C
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1ccc2c(c1)[nH]c1ccc(Oc3ncnc4cc(OCCCN5CCCCC5)ccc34)cc12
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
74
[{"value": 74.0, "product": "C1=CC(=CC=2C3=CC=CC=C3NC12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 73.8, "product": "C1=CC(=CC=2C3=CC=CC=C3NC12)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
85
CELSIUS
3
HOUR
A mixture of 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (200 mg, 0.595 mmol), (prepared as described for the starting material in Example 67), potassium carbonate (411 mg, 2.98 mmol) and 3-hydroxycarbazole (142 mg, 0.774 mmol) in DMA (2.0 ml) was stirred at 85° C. for 3 hours then allowed to cool to ambient ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2c(c1)[nH]c1ccccc12.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
CC(=O)N(C)C
85
3
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1ccc2[nH]c3ccccc3c2c1>CC(=O)N(C)C>COc1cc2c(Oc3ccc4[nH]c5ccccc5c4c3)ncnc2cc1OCCCN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-5420ffa646cf4180bb04913a9b4e2ddb
CCOC(=O)c1cc2cc(O)cc(Cl)c2[nH]1.COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1>>COc1ncc2ccc(OCCCN3CCCCC3)cc2n1.N
ClC=1C=C(C=C2C=C(NC12)C(=O)OCC)O.ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1.C([O-])([O-])=O.[K+].[K+]>>N.COC1=NC2=CC(=CC=C2C=N1)OCCCN1CCCCC1
CCOC(=O)c1cc2cc(O)cc(Cl)c2[nH:23]1.Cl[c:3]1[n:4][cH:5][n:22][c:21]2[c:6]1[cH:7][c:8]([O:2][CH3:1])[c:9]([O:10][CH2:11][CH2:12][CH2:13][N:14]1[CH2:15][CH2:16][CH2:17][CH2:18][CH2:19]1)[cH:20]2>>[CH3:1][O:2][c:3]1[n:4][cH:5][c:6]2[cH:7][cH:8][c:9]([O:10][CH2:11][CH2:12][CH2:13][N:14]3[CH2:15][CH2:16][CH2:17][CH2:18][CH2:...
CCOC(=O)c1cc2cc(O)cc(Cl)c2[nH]1.COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1
COc1ncc2ccc(OCCCN3CCCCC3)cc2n1.N
null
null
CC(=O)N(C)C
Heteroatom Alkylation and Arylation
OtherReaction
1f4a078a87a2cd24f5427d4b035f6072255d15c9e66b3a1d7b1eefefb95252f6
94b25ed96cf8c349fb5ad11a6cf51873bfff33948c723a93839df0af98ec2286
c1ncc2ccc(OCCCN3CCCCC3)cc2n1
C-C-O-C(=O)-c1:[nH;D2;+0:1]:c2:c(-Cl):c:c(-O):c:c:2:c:1.Cl-[c;H0;D3;+0:2]1:[#7;a:3]:[cH;D2;+0:4]:[n;H0;D2;+0:5]:[c:6]2:[c:7]:[c:8](-[#8:9]):[c;H0;D3;+0:10](-[O;H0;D2;+0:11]-[C;D1;H3:12]):[c:13]:[c;H0;D3;+0:14]:2:1>>[#8:9]-[c:8]1:[c:7]:[c:6]2:[n;H0;D2;+0:5]:[c;H0;D3;+0:2](-[O;H0;D2;+0:11]-[C;D1;H3:12]):[#7;a:3]:[cH;D2;+...
215.7
[{"value": 2.0, "product": "N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 63.0, "product": "COC1=NC2=CC(=CC=C2C=N1)OCCCN1CCCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 215.7, "product": "COC1=NC2=CC(=CC=C2C=N1)OCCCN1CCCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}...
100
CELSIUS
2
HOUR
A mixture of 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (84 mg, 0.24 mmol), (prepared as described for the starting material in Example 67), potassium carbonate (162 mg, 1.18 mmol) and ethyl 7-chloro-5-hydroxyindole-2-carboxylate (62 mg, 0.26 mmol) in DMA (2.0 ml) was stirred at 100° C. for 2 hours and allow...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Ester.Ether.Aromatic alcohol
Ether
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
CC(=O)N(C)C
100
2
CCOC(=O)c1cc2cc(O)cc(Cl)c2[nH]1.COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1>CC(=O)N(C)C>COc1ncc2ccc(OCCCN3CCCCC3)cc2n1.N
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b720bf58d91e480d8483df4e9d3bbf50
CCC(C)OC(=O)CC(C)=O.COc1ccc(N)c(Cl)c1>>CCOC(=O)c1cc2cc(OC)cc(Cl)c2[nH]1
ClC1=C(N)C=CC(=C1)OC.Cl.C(C)(=O)[O-].[Na+].S(O)(O)(=O)=O.N(=O)[O-].[Na+].C(CC(=O)C)(=O)OC(C)CC.[OH-].[K+]>>ClC=1C=C(C=C2C=C(NC12)C(=O)OCC)OC
C[CH2:1][CH:2](C)[O:3][C:4](=[O:5])[CH2:6][C:7](C)=O.[cH:8]1[cH:9][c:10]([O:11][CH3:12])[cH:13][c:14]([Cl:15])[c:16]1[NH2:17]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]2[cH:9][c:10]([O:11][CH3:12])[cH:13][c:14]([Cl:15])[c:16]2[nH:17]1
CCC(C)OC(=O)CC(C)=O.COc1ccc(N)c(Cl)c1
CCOC(=O)c1cc2cc(OC)cc(Cl)c2[nH]1
null
null
O.C(C)O
Aromatic Heterocycle Formation
OtherReaction
82a2f84f83ec62d512cf1b75ad27b27172bebc89925485b01b04151288b3e16b
c45a7acb285da3123c5d22eec0ca0a66ba4c84503de7af0b65f8f37d8156499c
c1ccc2[nH]ccc2c1
C-[CH2;D2;+0:1]-[CH;D3;+0:2](-C)-[#8:3]-[C:4](=[O;D1;H0:5])-[CH2;D2;+0:6]-[C;H0;D3;+0:7](-C)=O.[NH2;D1;+0:8]-[c:9](:[c:10]):[cH;D2;+0:11]:[c:12]:[c:13]>>[CH3;D1;+0:1]-[CH2;D2;+0:2]-[#8:3]-[C:4](=[O;D1;H0:5])-[c;H0;D3;+0:6]1:[cH;D2;+0:7]:[c;H0;D3;+0:11](:[c:12]:[c:13]):[c:9](:[c:10]):[nH;D2;+0:8]:1
4
[{"value": 4.0, "product": "ClC=1C=C(C=C2C=C(NC12)C(=O)OCC)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 3.5, "product": "ClC=1C=C(C=C2C=C(NC12)C(=O)OCC)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
-5
CELSIUS
4
HOUR
2-Chloro-4-methoxyaniline (2.719 g, 14 mmol) was added to 8.0M aqueous hydrochloric acid (15 ml) and the suspension cooled to −5° C. Sodium nitrite (1.063 g, 15.4 mmol) was added as a solution in water (3 ml). After addition the pH was brought to pH 4–5 by addition of sodium acetate. In a separate flask, ethyl-α-ethyl ...
10.6084/m9.figshare.5104873.v1
null
Ketone.Ester.Primary amine
Ester
c1ccccc1
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1
HO-
O.C(C)O
-5
4
CCC(C)OC(=O)CC(C)=O.COc1ccc(N)c(Cl)c1>O.C(C)O>CCOC(=O)c1cc2cc(OC)cc(Cl)c2[nH]1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b84b0cbdfc1d47a3b0b638876f5a0ba5
CCOC(=O)c1cc2cc(OC)cc(Cl)c2[nH]1>>CCOC(=O)c1cc2cc(O)cc(Cl)c2[nH]1
O.ClC=1C=C(C=C2C=C(NC12)C(=O)OCC)OC.B(Br)(Br)Br.[OH-].[Na+]>>ClC=1C=C(C=C2C=C(NC12)C(=O)OCC)O
C[O:11][c:10]1[cH:9][c:8]2[cH:7][c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[nH:16][c:15]2[c:13]([Cl:14])[cH:12]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][c:8]2[cH:9][c:10]([OH:11])[cH:12][c:13]([Cl:14])[c:15]2[nH:16]1
CCOC(=O)c1cc2cc(OC)cc(Cl)c2[nH]1
CCOC(=O)c1cc2cc(O)cc(Cl)c2[nH]1
null
null
ClCCl.C(Cl)Cl
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2[nH]ccc2c1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[OH;D1;+0:1]-[c:2](:[c:3]):[c:4]
71.1
[{"value": 71.0, "product": "ClC=1C=C(C=C2C=C(NC12)C(=O)OCC)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 71.1, "product": "ClC=1C=C(C=C2C=C(NC12)C(=O)OCC)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
-78
CELSIUS
30
MINUTE
To a solution of ethyl 7-chloro-5-methoxyindole-2-carboxylate (82 mg, 0.323 mmol) in dichloromethane (5 ml) at −78° C. was added boron tribromide (1.07 ml of a 1.0M solution in DCM, 1.07 mmol) and the reaction stirred at −78° C. for 30 minutes then allowed to warm to ambient temperature overnight. Water was carefully a...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1ccc2[nH]ccc2c1
Other
ClCCl.C(Cl)Cl
-78
0.5
CCOC(=O)c1cc2cc(OC)cc(Cl)c2[nH]1>ClCCl.C(Cl)Cl>CCOC(=O)c1cc2cc(O)cc(Cl)c2[nH]1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-4221763137304788ad96c9204309b884
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cc1[nH]c2ccc(O)cc2c1C>>COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCc1ccccc1
C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)Cl)OC.C([O-])([O-])=O.[K+].[K+].CC=1NC2=CC=C(C=C2C1C)O>>C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=C(NC2=CC1)C)C)OC
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:24]([O:25][CH2:26][c:27]3[cH:28][cH:29][cH:30][cH:31][cH:32]3)[cH:23][c:22]2[n:21][cH:20][n:19]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][c:13]([CH3:14])[c:15]([CH3:16])[c:17]2[cH:18]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[c:...
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cc1[nH]c2ccc(O)cc2c1C
COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCc1ccccc1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1ccc(COc2ccc3c(Oc4ccc5[nH]ccc5c4)ncnc3c2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
46
[{"value": 46.0, "product": "C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=C(NC2=CC1)C)C)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 46.0, "product": "C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C(=C(NC2=CC1)C)C)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
2
HOUR
A mixture of 7-benzyloxy-4-chloro-6-methoxyquinazoline (1.5 g, 4.99 mmol), (prepared as described for the starting material in Example 1), potassium carbonate (2.07 g, 15 mmol) and 2,3-dimethyl-5-hydroxyindole (1.21 g, 7.5 mmol), (Arch. Pharm. 1972, 305, 159), in DMF (75 ml) was stirred at 100° C. for 2 hours and allow...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.c1ccccc1
HCl
CN(C)C=O
100
2
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cc1[nH]c2ccc(O)cc2c1C>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)c(C)c4c3)ncnc2cc1OCc1ccccc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-5d09da4ac3df44b0980281c44d3d8b4a
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Oc1ccc2ccccc2n1>>COc1cc2c(Oc3ccc4ccccc4n3)ncnc2cc1OCCCN1CCOCC1
[OH-].[Na+].ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1.C([O-])([O-])=O.[K+].[K+].OC1=NC2=CC=CC=C2C=C1>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)OC1=NC2=CC=CC=C2C=C1
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:23]([O:24][CH2:25][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][cH:13][cH:14][cH:15][c:16]2[n:17]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[cH:12][cH:13][cH:1...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Oc1ccc2ccccc2n1
COc1cc2c(Oc3ccc4ccccc4n3)ncnc2cc1OCCCN1CCOCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1ccc2nc(Oc3ncnc4cc(OCCCN5CCOCC5)ccc34)ccc2c1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[#7;a:12]:[c:13]>>[c:13]:[#7;a:12]:[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:11]
11
[{"value": 11.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)OC1=NC2=CC=CC=C2C=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 11.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)OC1=NC2=CC=CC=C2C=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
5
HOUR
A mixture of 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (225 mg, 0.67 mmol), (prepared as described for the starting material in Example 1), potassium carbonate (106 mg, 0.77 mmol) and 2-hydroxyquinoline (111 mg, 0.76 mmol) in DMF (7.5 ml) was stirred at 100° C. for 5 hours and allowed to cool to ambient tem...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncccc2c1.c1ccc2ncncc2c1.C1COCC[NH]1
HCl
CN(C)C=O
100
5
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Oc1ccc2ccccc2n1>CN(C)C=O>COc1cc2c(Oc3ccc4ccccc4n3)ncnc2cc1OCCCN1CCOCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e4ec6c08da654f7997c0a4f544c47d32
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Oc1cccc2ncccc12>>COc1cc2c(Oc3cccc4ncccc34)ncnc2cc1OCCCN1CCOCC1
[OH-].[Na+].ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1.C([O-])([O-])=O.[K+].[K+].OC1=C2C=CC=NC2=CC=C1>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)OC1=C2C=CC=NC2=CC=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][cH:11][c:12]2[n:13][cH:14][cH:15][cH:16][c:17]12>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][cH:11][c:12]4[n:13][cH:14...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Oc1cccc2ncccc12
COc1cc2c(Oc3cccc4ncccc34)ncnc2cc1OCCCN1CCOCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1cc(Oc2ncnc3cc(OCCCN4CCOCC4)ccc23)c2cccnc2c1
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]
59.5
[{"value": 59.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)OC1=C2C=CC=NC2=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 59.5, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)OC1=C2C=CC=NC2=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
5
HOUR
A mixture of 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (225 mg, 0.67 mmol), (prepared as described for the starting material in Example 1), potassium carbonate (106 mg, 0.77 mmol) and 5-hydroxyquinoline (111 mg, 0.77 mmol) in DMF (7.5 ml) was stirred at 100° C. for 5 hours and allowed to cool to ambient tem...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncccc2c1.c1ccc2ncncc2c1.C1COCC[NH]1
HCl
CN(C)C=O
100
5
COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1.Oc1cccc2ncccc12>CN(C)C=O>COc1cc2c(Oc3cccc4ncccc34)ncnc2cc1OCCCN1CCOCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-38211a4e4b754ee4b088506079758e11
COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1.Oc1ccc2cccnc2c1>>COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCCCN1CCN(C)CC1
[OH-].[Na+].ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C.C([O-])([O-])=O.[K+].[K+].OC1=CC=C2C=CC=NC2=C1>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCN(CC1)C)OC1=CC=C2C=CC=NC2=C1
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:23]([O:24][CH2:25][CH2:26][CH2:27][N:28]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[cH:12][cH:13][cH:14][n:15][c:16]2[cH:17]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[cH:12][c...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1.Oc1ccc2cccnc2c1
COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCCCN1CCN(C)CC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1cnc2cc(Oc3ncnc4cc(OCCCN5CCNCC5)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]
39
[{"value": 39.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCN(CC1)C)OC1=CC=C2C=CC=NC2=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 38.9, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCN(CC1)C)OC1=CC=C2C=CC=NC2=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
5
HOUR
A mixture of 4-chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline (200 mg, 0.57 mmol), potassium carbonate (106 mg, 0.77 mmol) and 7-hydroxyquinoline (111 mg, 0.76 mmol) in DMF (7 ml) was stirred at 100° C. for 5 hours and allowed to cool to ambient temperature. The reaction mixture was treated with 1.0 ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncccc2c1.c1ccc2ncncc2c1.C1C[NH]CC[NH]1
HCl
CN(C)C=O
100
5
COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1.Oc1ccc2cccnc2c1>CN(C)C=O>COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCCCN1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-00871006f26b4344bb664f8a0a7014cc
CN1CCN(CCCO)CC1.Cc1ccc(S(=O)(=O)Cl)cc1>>Cc1ccc(S(=O)(=O)OCCCN2CCN(C)CC2)cc1
OCCCN1CCN(CC1)C.C(C)N(CC)CC.C1(=CC=C(C=C1)S(=O)(=O)Cl)C>>CN1CCN(CC1)CCCOS(=O)(=O)C1=CC=C(C=C1)C
[OH:9][CH2:10][CH2:11][CH2:12][N:13]1[CH2:14][CH2:15][N:16]([CH3:17])[CH2:18][CH2:19]1.Cl[S:6]([c:5]1[cH:4][cH:3][c:2]([CH3:1])[cH:21][cH:20]1)(=[O:7])=[O:8]>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([S:6](=[O:7])(=[O:8])[O:9][CH2:10][CH2:11][CH2:12][N:13]2[CH2:14][CH2:15][N:16]([CH3:17])[CH2:18][CH2:19]2)[cH:20][cH:21]1
CN1CCN(CCCO)CC1.Cc1ccc(S(=O)(=O)Cl)cc1
Cc1ccc(S(=O)(=O)OCCCN2CCN(C)CC2)cc1
null
null
ClCCl
Acylation
Formation of Sulfonic Esters
d05d91207659f8fa672c205a316a670adfe2b92492fc9adad2ee3f241e574fb9
a7748b0f3b0eba3868d0cf03ae67721db046202accaaea9cadb4edbc96ec8768
O=S(=O)(OCCCN1CCNCC1)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]
null
[]
null
null
2
HOUR
A solution of 1-(3-hydroxypropyl)-4-methylpiperazine (2.4 g, 15 mmol), (prepared as described for the starting material in Example 133), in dichloromethane (60 ml) was treated with triethylamine (4.6 ml, 33 mmol) and p-toluenesulphonyl chloride (3.2 g, 17 mmol) and stirred at ambient temperature for 2 hours. The soluti...
10.6084/m9.figshare.5104873.v1
null
Tosylate.Primary alcohol.Sulfonyl halide
Tosylate
null
null
c1ccccc1.C1C[NH]CC[NH]1
HCl
ClCCl
null
2
CN1CCN(CCCO)CC1.Cc1ccc(S(=O)(=O)Cl)cc1>ClCCl>Cc1ccc(S(=O)(=O)OCCCN2CCN(C)CC2)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d9aee196fb0c45a69e6970ec9680d477
COc1cc(C(N)=O)c(N)cc1OCc1ccccc1>>COc1cc2c(=O)[nH]cnc2cc1OCc1ccccc1
NC1=C(C(=O)N)C=C(C(=C1)OCC1=CC=CC=C1)OC.CN(C)C=NC=[N+](C)C.[Cl-].C(C)(=O)[O-].[Na+].C(C)(=O)O>>C(C1=CC=CC=C1)OC1=C(C=C2C(NC=NC2=C1)=O)OC
[CH3:1][O:2][c:3]1[cH:4][c:5]([C:6](=[O:7])[NH2:8])[c:11]([NH2:10])[cH:12][c:13]1[O:14][CH2:15][c:16]1[cH:17][cH:18][cH:19][cH:20][cH:21]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6](=[O:7])[nH:8][cH:9][n:10][c:11]2[cH:12][c:13]1[O:14][CH2:15][c:16]1[cH:17][cH:18][cH:19][cH:20][cH:21]1
COc1cc(C(N)=O)c(N)cc1OCc1ccccc1
COc1cc2c(=O)[nH]cnc2cc1OCc1ccccc1
null
null
O1CCOCC1
Aromatic Heterocycle Formation
OtherReaction
0798449d56bc7e7756a703d33bd60780d26c4986e39e1809e15228456c95135b
3074b6c74bc99545969aa05d42dae7b149d9d6bb1b36a52cec3a362e1e7f7ca0
O=c1[nH]cnc2cc(OCc3ccccc3)ccc12
[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4](-[C;H0;D3;+0:5](-[NH2;D1;+0:6])=[O;D1;H0:7]):[c:8]>>[O;D1;H0:7]=[c;H0;D3;+0:5]1:[nH;D2;+0:6]:[c:9]:[n;H0;D2;+0:1]:[c:2](:[c:3]):[c:4]:1:[c:8]
84
[{"value": 84.0, "product": "C(C1=CC=CC=C1)OC1=C(C=C2C(NC=NC2=C1)=O)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 77.0, "product": "C(C1=CC=CC=C1)OC1=C(C=C2C(NC=NC2=C1)=O)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A mixture of 2-amino-4-benzyloxy-5-methoxybenzamide (J. Med. Chem. 1977, vol 20, 146–149, 10 g, 0.04 mol) and Gold's reagent (7.4 g, 0.05 mol) in dioxane (100 ml) was stirred and heated at reflux for 24 hours. Sodium acetate (3.02 g, 0.037 mol) and acetic acid (1.65 ml, 0.029 mol) were added to the reaction mixture and...
10.6084/m9.figshare.5104873.v1
null
Primary amide.Primary amine
null
c1ccccc1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.c1ccccc1
Other
O1CCOCC1
null
null
COc1cc(C(N)=O)c(N)cc1OCc1ccccc1>O1CCOCC1>COc1cc2c(=O)[nH]cnc2cc1OCc1ccccc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a632f4224c1a43a8b4f45d262cdce4eb
COc1cc2c(=O)[nH]cnc2cc1OCc1ccccc1.O=S(Cl)Cl>>COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cl
C(C1=CC=CC=C1)OC1=C(C=C2C(NC=NC2=C1)=O)OC.S(=O)(Cl)Cl>>Cl.C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)Cl)OC
O=[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:13]([O:14][CH2:15][c:16]3[cH:17][cH:18][cH:19][cH:20][cH:21]3)[cH:12][c:11]2[n:10][cH:9][nH:8]1.O=S([Cl:7])[Cl:22]>>[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:16]1[cH:17][cH:18][cH:19][cH:20][cH:21]1.[ClH:22]
COc1cc2c(=O)[nH]cnc2cc1OCc1ccccc1.O=S(Cl)Cl
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cl
null
null
CN(C)C=O
Functional Group Interconversion
OtherReaction
3788560e87eee8765e749543914a91a512631307b97fad163ebef894d2a0ea68
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccc(COc2ccc3cncnc3c2)cc1
O=S(-[Cl;H0;D1;+0:1])-[Cl;H0;D1;+0:2].O=[c;H0;D3;+0:3]1:[nH;D2;+0:4]:[c:5]:[#7;a:6]:[c:7](:[c:8]):[c:9]:1:[c:10]>>[Cl;H0;D1;+0:2]-[c;H0;D3;+0:3]1:[n;H0;D2;+0:4]:[c:5]:[#7;a:6]:[c:7](:[c:8]):[c:9]:1:[c:10].[ClH;D0;+0:1]
null
[]
null
null
null
null
A mixture of 7-benzyloxy-6-methoxy-3,4-dihydroquinazolin-4-one (2.82 g, 0.01 mol), thionyl chloride (40 ml) and DMF (0.28 ml) was stirred and heated at reflux for 1 hour. The mixture was evaporated and azeotroped with toluene to give 7-benzyloxy-4-chloro-6-methoxyquinazoline hydrochloride (3.45 g). Conditions: See reac...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.c1ccccc1
Other
CN(C)C=O
null
null
COc1cc2c(=O)[nH]cnc2cc1OCc1ccccc1.O=S(Cl)Cl>CN(C)C=O>COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cl
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-fdab2a2d61764a5eb1313b4fbd993e77
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Oc1ccc(Cl)cc1F>>COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1
ClC1=CC(=C(C=C1)O)F.Cl.C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)Cl)OC>>C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC1=C(C=C(C=C1)Cl)F)OC
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:21]([O:22][CH2:23][c:24]3[cH:25][cH:26][cH:27][cH:28][cH:29]3)[cH:20][c:19]2[n:18][cH:17][n:16]1.[OH:7][c:8]1[cH:9][cH:10][c:11]([Cl:12])[cH:13][c:14]1[F:15]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]([Cl:12])[cH:13][c:14]3[F:15])[n:16][cH:17][n:18][c:1...
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Oc1ccc(Cl)cc1F
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1
null
null
N1=CC=CC=C1
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1ccc(COc2ccc3c(Oc4ccccc4)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]
77
[{"value": 77.0, "product": "C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC1=C(C=C(C=C1)Cl)F)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 76.9, "product": "C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC1=C(C=C(C=C1)Cl)F)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
4-Chloro-2-fluoro-phenol (264 mg, 1.8 mmol) was added to a solution of 7-benzyloxy-4-chloro-6-methoxyquinazoline hydrochloride (506 mg, 1.5 mmol) in pyridine (8 ml) and the mixture heated at reflux for 45 minutes. The solvent was removed by evaporation and the residue partitioned between ethyl acetate and water. The or...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccccc1.c1ccc2ncncc2c1.c1ccccc1
HCl
N1=CC=CC=C1
null
null
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Oc1ccc(Cl)cc1F>N1=CC=CC=C1>COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-85135f206b204869838501aa1ca971d5
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1>>COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1O
C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC1=C(C=C(C=C1)Cl)F)OC>>ClC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)O)C=C1)F
c1ccc(C[O:22][c:21]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]([Cl:12])[cH:13][c:14]4[F:15])[n:16][cH:17][n:18][c:19]3[cH:20]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]([Cl:12])[cH:13][c:14]3[F:15])[n:16][cH:17][n:18][c:19]2[cH:20][c:21]1[OH:22]
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1O
null
null
C1(=CC=CC=C1)C.C(=O)(C(F)(F)F)O
Deprotection
Hydroxyl benzyl deprotection
36869d1fe85185a14d9eb30bf05178c600a9b6eca277ffaf3803578c30e0bf5d
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc(Oc2ncnc3ccccc23)cc1
[#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]
90.7
[{"value": 90.0, "product": "ClC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)O)C=C1)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 90.7, "product": "ClC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)O)C=C1)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 7-benzyloxy-4-(4-chloro-2-fluorophenoxy)-6-methoxyquinazoline (451 mg, 1.1 mmol) in TFA (4.5 ml) was heated at reflux for 3 hours. The mixture was diluted with toluene and the volatiles removed by evaporation. The residue was triturated with methylene chloride, collected by filtration, washed with ether a...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
c1ccccc1
null
c1ccccc1.c1ccc2ncncc2c1
Other
C1(=CC=CC=C1)C.C(=O)(C(F)(F)F)O
null
null
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1OCc1ccccc1>C1(=CC=CC=C1)C.C(=O)(C(F)(F)F)O>COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-dc4b8fce3c9d43948548a1d1d49422d6
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1O.Cc1ccc(S(=O)(=O)OCCCN2CCN(C)CC2)cc1>>COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1OCCCN1CCN(C)CC1
FC(C(=O)O)(F)F.ClC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)O)C=C1)F.C([O-])([O-])=O.[K+].[K+].CN1CCN(CC1)CCCOS(=O)(=O)C1=CC=C(C=C1)C>>ClC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)OCCCN2CCN(CC2)C)C=C1)F
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]([Cl:12])[cH:13][c:14]3[F:15])[n:16][cH:17][n:18][c:19]2[cH:20][c:21]1[OH:22].Cc1ccc(S(=O)(=O)O[CH2:23][CH2:24][CH2:25][N:26]2[CH2:27][CH2:28][N:29]([CH3:30])[CH2:31][CH2:32]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]([Cl:12...
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1O.Cc1ccc(S(=O)(=O)OCCCN2CCN(C)CC2)cc1
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1OCCCN1CCN(C)CC1
null
null
O.CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
b5213736859cf91483a02f350869986d9b7674724716adef8a5d7a4bbdb79574
3d107e624e135e10014c7bf413dd0be27e1e4488f039e545b94cb1680b764158
c1ccc(Oc2ncnc3cc(OCCCN4CCNCC4)ccc23)cc1
C-c1:c:c:c(-S(=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]
48.1
[{"value": 48.0, "product": "ClC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)OCCCN2CCN(CC2)C)C=C1)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 48.1, "product": "ClC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)OCCCN2CCN(CC2)C)C=C1)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
90
CELSIUS
5
HOUR
A mixture of the trifluoroacetic acid salt of 4-(4-chloro-2-fluorophenoxy)-7-hydroxy-6-methoxyquinazoline (3.2 g, 7.4 mmol), potassium carbonate (6.1 g, 44.2 mmol) and 3-(4-methyl-1-piperazinyl)propyl-4-toluene sulphonate (3.0 g, 9.6 mmol) in DMF (60 ml) was stirred at 90° C. for 5 hours and allowed to cool to ambient ...
10.6084/m9.figshare.5104873.v1
null
Tosylate.Aromatic alcohol
Ether
c1ccccc1
null
c1ccccc1.c1ccc2ncncc2c1.C1C[NH]CC[NH]1
TsOH.HO-
O.CN(C)C=O
90
5
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1O.Cc1ccc(S(=O)(=O)OCCCN2CCN(C)CC2)cc1>O.CN(C)C=O>COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1OCCCN1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-ce966b7d00e34720838fdfe6a72f7ac8
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1OCCCN1CCN(C)CC1>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCN(C)CC1
ClC1=CC(=C(OC2=NC=NC3=CC(=C(C=C23)OC)OCCCN2CCN(CC2)C)C=C1)F.Cl.C(O)([O-])=O.[Na+]>>COC=1C=C2C(NC=NC2=CC1OCCCN1CCN(CC1)C)=O
Fc1cc(Cl)ccc1[O:7][c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:13]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:19][CH2:20][N:21]([CH3:22])[CH2:23][CH2:24]3)[cH:12][c:11]2[n:10][cH:9][n:8]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6](=[O:7])[nH:8][cH:9][n:10][c:11]2[cH:12][c:13]1[O:14][CH2:15][CH2:16][CH2:17][N:18]1[CH2:19][CH2:20][N...
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1OCCCN1CCN(C)CC1
COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCN(C)CC1
null
null
null
Functional Group Interconversion
OtherReaction
2e331e7f987e2f208a7bb6621e9b7dc6ca9e78c94b181dc5496a50196c7c48fe
a99fd2343850f6fbc4a4d7024846a70661aad8ef3f77938589a06d4940f99c06
O=c1[nH]cnc2cc(OCCCN3CCNCC3)ccc12
Cl-c1:c:c:c(-[O;H0;D2;+0:1]-[c;H0;D3;+0:2]2:[n;H0;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:2:[c:9]):c(-F):c:1>>[O;H0;D1;+0:1]=[c;H0;D3;+0:2]1:[nH;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]
96.7
[{"value": 96.0, "product": "COC=1C=C2C(NC=NC2=CC1OCCCN1CCN(CC1)C)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 96.7, "product": "COC=1C=C2C(NC=NC2=CC1OCCCN1CCN(CC1)C)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
95
CELSIUS
2
HOUR
4-(4-Chloro-2-fluorophenoxy)-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline (2.6 g, 5.6 mmol) was treated with 2.0 N aqueous hydrochloric acid (45 ml) and the mixture stirred at 95° C. for 2 hours. The mixture was cooled, basified by the addition of solid sodium hydrogen carbonate and the water removed by a...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Ether
null
c1ccccc1.c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1C[NH]CC[NH]1
HF
null
95
2
COc1cc2c(Oc3ccc(Cl)cc3F)ncnc2cc1OCCCN1CCN(C)CC1>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d681da44a84f414cbd789e378199dd48
COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCN(C)CC1.O=S(Cl)Cl>>COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1
COC=1C=C2C(NC=NC2=CC1OCCCN1CCN(CC1)C)=O.CN(C)C=O.S(=O)(Cl)Cl>>ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C
O=[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:13]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:19][CH2:20][N:21]([CH3:22])[CH2:23][CH2:24]3)[cH:12][c:11]2[n:10][cH:9][nH:8]1.O=S(Cl)[Cl:7]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([Cl:7])[n:8][cH:9][n:10][c:11]2[cH:12][c:13]1[O:14][CH2:15][CH2:16][CH2:17][N:18]1[CH2:19][CH2:20][N:2...
COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCN(C)CC1.O=S(Cl)Cl
COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1
null
null
null
Functional Group Interconversion
OtherReaction
3788560e87eee8765e749543914a91a512631307b97fad163ebef894d2a0ea68
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ncc2ccc(OCCCN3CCNCC3)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]
53
[{"value": 53.0, "product": "ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
6-Methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)-3,4-dihydroquinazolin-4-one (2.15 g, 6.48 mmol) was suspended in thionyl chloride (25 ml) and DMF (0.18 ml) and stirred under reflux for 2 hours. The thionyl chloride was evaporated under vacuum and the residue azeotroped twice with toluene. The residue was taken up in wa...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1C[NH]CC[NH]1
HCl
null
null
null
COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCN(C)CC1.O=S(Cl)Cl>>COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d3eddadf507f41a091a405d3f00e1f6e
COCCOCCOc1cc2ncnc(Cl)c2cc1OC.Oc1ccc2cccnc2c1>>COCCOCCOc1cc2ncnc(Oc3ccc4cccnc4c3)c2cc1OC
O.ClC1=NC=NC2=CC(=C(C=C12)OC)OCCOCCOC.C([O-])([O-])=O.[K+].[K+].OC1=CC=C2C=CC=NC2=C1>>COC=1C=C2C(=NC=NC2=CC1OCCOCCOC)OC1=CC=C2C=CC=NC2=C1
Cl[c:15]1[n:14][cH:13][n:12][c:11]2[cH:10][c:9]([O:8][CH2:7][CH2:6][O:5][CH2:4][CH2:3][O:2][CH3:1])[c:29]([O:30][CH3:31])[cH:28][c:27]21.[OH:16][c:17]1[cH:18][cH:19][c:20]2[cH:21][cH:22][cH:23][n:24][c:25]2[cH:26]1>>[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][CH2:7][O:8][c:9]1[cH:10][c:11]2[n:12][cH:13][n:14][c:15]([O:16][c...
COCCOCCOc1cc2ncnc(Cl)c2cc1OC.Oc1ccc2cccnc2c1
COCCOCCOc1cc2ncnc(Oc3ccc4cccnc4c3)c2cc1OC
null
null
CS(=O)C
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1cnc2cc(Oc3ncnc4ccccc34)ccc2c1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#7;a:9]:[c:10]:[c:11]:[c:12](-[OH;D1;+0:13]):[c:14]>>[#7;a:9]:[c:10]:[c:11]:[c:12](-[O;H0;D2;+0:13]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:14]
55
[{"value": 55.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCOCCOC)OC1=CC=C2C=CC=NC2=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 54.9, "product": "COC=1C=C2C(=NC=NC2=CC1OCCOCCOC)OC1=CC=C2C=CC=NC2=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
5
HOUR
A mixture of 4-chloro-6-methoxy-7-(2-(2-methoxyethoxy)ethoxy)quinazoline (200 mg, 0.64 mmol), potassium carbonate (102 mg, 0.74 mmol) and 7-hydroxyquinoline (107 mg, 0.74 mmol) in DMSO (5 ml) was stirred at 100° C. for 5 hours and allowed to cool to ambient temperature. The mixture was poured into water, washed with di...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.c1ccc2ncccc2c1
HCl
CS(=O)C
100
5
COCCOCCOc1cc2ncnc(Cl)c2cc1OC.Oc1ccc2cccnc2c1>CS(=O)C>COCCOCCOc1cc2ncnc(Oc3ccc4cccnc4c3)c2cc1OC
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-35ccd4e13712472a93ab2b61e84e6b9f
COCCOCCO.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O>>COCCOCCOc1cc2ncn(COC(=O)C(C)(C)C)c(=O)c2cc1OC
COCCOCCO.N(=NC(=O)OCC)C(=O)OCC.OC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1>>COC=1C=C2C(N(C=NC2=CC1OCCOCCOC)COC(C(C)(C)C)=O)=O
O[CH2:7][CH2:6][O:5][CH2:4][CH2:3][O:2][CH3:1].[OH:8][c:9]1[cH:10][c:11]2[n:12][cH:13][n:14]([CH2:15][O:16][C:17](=[O:18])[C:19]([CH3:20])([CH3:21])[CH3:22])[c:23](=[O:24])[c:25]2[cH:26][c:27]1[O:28][CH3:29]>>[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][CH2:7][O:8][c:9]1[cH:10][c:11]2[n:12][cH:13][n:14]([CH2:15][O:16][C:17](...
COCCOCCO.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O
COCCOCCOc1cc2ncn(COC(=O)C(C)(C)C)c(=O)c2cc1OC
null
null
C(Cl)Cl
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
O=c1[nH]cnc2ccccc12
O-[CH2;D2;+0:1]-[C:2]-[#8:3].[#7;a:4]:[c:5]:[c:6]:[c:7](-[OH;D1;+0:8]):[c:9]>>[#7;a:4]:[c:5]:[c:6]:[c:7](-[O;H0;D2;+0:8]-[CH2;D2;+0:1]-[C:2]-[#8:3]):[c:9]
106.7
[{"value": 100.0, "product": "COC=1C=C2C(N(C=NC2=CC1OCCOCCOC)COC(C(C)(C)C)=O)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 106.7, "product": "COC=1C=C2C(N(C=NC2=CC1OCCOCCOC)COC(C(C)(C)C)=O)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
1.5
HOUR
Diethyl azodicarboxylate (864 μl, 5.5 mmol) was added dropwise to a mixture of 7-hydroxy-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (1.2 g, 3.9 mmol) (prepared as described for the starting material in Example 12), triphenylphosphine (1.44 g, 5.5 mmol) and 2-(2-methoxyethoxy)ethanol (653 μl, 5.5 mmol...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccc2ncncc2c1
HO-
C(Cl)Cl
0
1.5
COCCOCCO.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O>C(Cl)Cl>COCCOCCOc1cc2ncn(COC(=O)C(C)(C)C)c(=O)c2cc1OC
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-784e8afcd41e42f19330f8334793a087
COCCOCCOc1cc2ncn(COC(=O)C(C)(C)C)c(=O)c2cc1OC>>COCCOCCOc1cc2nc[nH]c(=O)c2cc1OC
N.COC=1C=C2C(N(C=NC2=CC1OCCOCCOC)COC(C(C)(C)C)=O)=O.N>>COC=1C=C2C(NC=NC2=CC1OCCOCCOC)=O
CC(C)(C)C(=O)OC[n:14]1[cH:13][n:12][c:11]2[cH:10][c:9]([O:8][CH2:7][CH2:6][O:5][CH2:4][CH2:3][O:2][CH3:1])[c:19]([O:20][CH3:21])[cH:18][c:17]2[c:15]1=[O:16]>>[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][CH2:7][O:8][c:9]1[cH:10][c:11]2[n:12][cH:13][nH:14][c:15](=[O:16])[c:17]2[cH:18][c:19]1[O:20][CH3:21]
COCCOCCOc1cc2ncn(COC(=O)C(C)(C)C)c(=O)c2cc1OC
COCCOCCOc1cc2nc[nH]c(=O)c2cc1OC
null
null
C(Cl)Cl.C(C)O
Reduction
OtherReaction
9f6991089c15fc054898797f1d3a42b158e517f125611bc103acfc00878b3b20
b8e5da8ea19c403a2e974791a9cf591400749acb6b71151717aaece4f3b22bef
O=c1[nH]cnc2ccccc12
C-C(-C)(-C)-C(=O)-O-C-[n;H0;D3;+0:1]1:[c:2]:[#7;a:3]:[c:4]:[c:5]:[c:6]:1=[O;D1;H0:7]>>[O;D1;H0:7]=[c:6]1:[c:5]:[c:4]:[#7;a:3]:[c:2]:[nH;D2;+0:1]:1
78
[{"value": 78.0, "product": "COC=1C=C2C(NC=NC2=CC1OCCOCCOC)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 60.2, "product": "COC=1C=C2C(NC=NC2=CC1OCCOCCOC)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
24
HOUR
Saturated methanolic ammonia (20 ml) was added to a solution of 6-methoxy-7-(2-(2-methoxyethoxy)ethoxy)-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (2.26 g, 5.5 mmol) in a mixture of ethanol (40 ml) and methylene chloride (15 ml). The mixture was stirred for 24 hours at ambient temperature, and further methanol...
10.6084/m9.figshare.5104873.v1
null
Ester
null
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1
HO-
C(Cl)Cl.C(C)O
null
24
COCCOCCOc1cc2ncn(COC(=O)C(C)(C)C)c(=O)c2cc1OC>C(Cl)Cl.C(C)O>COCCOCCOc1cc2nc[nH]c(=O)c2cc1OC
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-30ee7078ab034fc7a1499a0f7c2a6156
COCCOCCOc1cc2nc[nH]c(=O)c2cc1OC.O=S(Cl)Cl>>COCCOCCOc1cc2ncnc(Cl)c2cc1OC
COC=1C=C2C(NC=NC2=CC1OCCOCCOC)=O.S(=O)(Cl)Cl>>ClC1=NC=NC2=CC(=C(C=C12)OC)OCCOCCOC
O=[c:15]1[nH:14][cH:13][n:12][c:11]2[cH:10][c:9]([O:8][CH2:7][CH2:6][O:5][CH2:4][CH2:3][O:2][CH3:1])[c:19]([O:20][CH3:21])[cH:18][c:17]21.O=S(Cl)[Cl:16]>>[CH3:1][O:2][CH2:3][CH2:4][O:5][CH2:6][CH2:7][O:8][c:9]1[cH:10][c:11]2[n:12][cH:13][n:14][c:15]([Cl:16])[c:17]2[cH:18][c:19]1[O:20][CH3:21]
COCCOCCOc1cc2nc[nH]c(=O)c2cc1OC.O=S(Cl)Cl
COCCOCCOc1cc2ncnc(Cl)c2cc1OC
null
null
CN(C)C=O
Functional Group Interconversion
OtherReaction
3788560e87eee8765e749543914a91a512631307b97fad163ebef894d2a0ea68
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccc2ncncc2c1
Cl-S(=O)-[Cl;H0;D1;+0:1].O=[c;H0;D3;+0:2]1:[nH;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:2]1:[n;H0;D2;+0:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]
87
[{"value": 87.0, "product": "ClC1=NC=NC2=CC(=C(C=C12)OC)OCCOCCOC", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 6-methoxy-7-(2-(2-methoxyethoxy)ethoxy)-3,4-dihydroquinazolin-4-one (930 mg, 3.16 mmol) in thionyl chloride (15 ml) and DMF (150 μl) was heated at 60° C. for 1.5 hours. The mixture was allowed to cool and the volatiles were removed by evaporation and by azeotroping with toluene. The residue was dissolved ...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1
HCl
CN(C)C=O
null
null
COCCOCCOc1cc2nc[nH]c(=O)c2cc1OC.O=S(Cl)Cl>CN(C)C=O>COCCOCCOc1cc2ncnc(Cl)c2cc1OC
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-6810790b5ad8493290ee02a8938ad3c6
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Cc1c[nH]c2ccc(O)cc12>>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCCCN1CCCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1.C([O-])([O-])=O.[K+].[K+].CC1=CNC2=CC=C(C=C12)O>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCCC1)OC=1C=C2C(=CNC2=CC1)C
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:23]([O:24][CH2:25][CH2:26][CH2:27][N:28]3[CH2:29][CH2:30][CH2:31][CH2:32][CH2:33]3)[cH:22][c:21]2[n:20][cH:19][n:18]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][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]...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Cc1c[nH]c2ccc(O)cc12
COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)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]
69.4
[{"value": 69.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCCC1)OC=1C=C2C(=CNC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 69.4, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCCC1)OC=1C=C2C(=CNC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
3
HOUR
A mixture of 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (168 mg, 0.5 mmol), (prepared as described for the starting material in Example 67), potassium carbonate (207 mg, 1.5 mmol), 3-methyl-5-hydroxyindole (88 mg, 0.6 mmol), (Can. J. Chem. 1964, 42, 514), and DMA (2.0 ml) was purged with nitrogen for 5 minut...
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
100
3
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Cc1c[nH]c2ccc(O)cc12>CC(=O)N(C)C>COc1cc2c(Oc3ccc4[nH]cc(C)c4c3)ncnc2cc1OCCCN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-f62b14e0a79642679a6502437d71f53f
COc1cc2c(Oc3ccccc3)ncnc2cc1O.ClCCN1CCCCC1>>COc1cc2c(Oc3ccccc3)ncnc2cc1OCCN1CCCCC1
Cl.ClCCN1CCCCC1.OC1=C(C=C2C(=NC=NC2=C1)OC1=CC=CC=C1)OC.C([O-])([O-])=O.[K+].[K+]>>COC=1C=C2C(=NC=NC2=CC1OCCN1CCCCC1)OC1=CC=CC=C1
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][cH:11][cH:12][cH:13]3)[n:14][cH:15][n:16][c:17]2[cH:18][c:19]1[OH:20].Cl[CH2:21][CH2:22][N:23]1[CH2:24][CH2:25][CH2:26][CH2:27][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][cH:11][cH:12][cH:13]3)[n:14][cH:15][n:16][c:17]2[cH:18][c:19...
COc1cc2c(Oc3ccccc3)ncnc2cc1O.ClCCN1CCCCC1
COc1cc2c(Oc3ccccc3)ncnc2cc1OCCN1CCCCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
c1ccc(Oc2ncnc3cc(OCCN4CCCCC4)ccc23)cc1
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]
85
[{"value": 85.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCN1CCCCC1)OC1=CC=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 84.8, "product": "COC=1C=C2C(=NC=NC2=CC1OCCN1CCCCC1)OC1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
110
CELSIUS
null
null
1-(2-Chloroethyl)piperidine hydrochloride (0.83 g, 4.5 mmol) was added to 7-hydroxy-6-methoxy-4-phenoxyquinazoline (1.0 g, 3.73 mmol), (prepared as described for the starting material in Example 1), and potassium carbonate (2.6 g, 18.8 mmol) in DMF (30 ml), and the mixture heated at 110° C. for 2.5 hours and allowed to...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
CN(C)C=O
110
null
COc1cc2c(Oc3ccccc3)ncnc2cc1O.ClCCN1CCCCC1>CN(C)C=O>COc1cc2c(Oc3ccccc3)ncnc2cc1OCCN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3a79667529d5461bbfecc7604871592f
COc1cc2c(=O)[nH]cnc2cc1OCCN1CCCCC1.O=S(Cl)Cl>>COc1cc2c(Cl)ncnc2cc1OCCN1CCCCC1.Cl
COC=1C=C2C(NC=NC2=CC1OCCN1CCCCC1)=O.S(=O)(Cl)Cl>>Cl.ClC1=NC=NC2=CC(=C(C=C12)OC)OCCN1CCCCC1
O=[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:13]([O:14][CH2:15][CH2:16][N:17]3[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22]3)[cH:12][c:11]2[n:10][cH:9][nH:8]1.O=S([Cl:7])[Cl:23]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([Cl:7])[n:8][cH:9][n:10][c:11]2[cH:12][c:13]1[O:14][CH2:15][CH2:16][N:17]1[CH2:18][CH2:19][CH2:20][CH2:21][CH2:22...
COc1cc2c(=O)[nH]cnc2cc1OCCN1CCCCC1.O=S(Cl)Cl
COc1cc2c(Cl)ncnc2cc1OCCN1CCCCC1.Cl
null
CN(C)C=O
null
Functional Group Interconversion
OtherReaction
3788560e87eee8765e749543914a91a512631307b97fad163ebef894d2a0ea68
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ncc2ccc(OCCN3CCCCC3)cc2n1
O=S(-[Cl;H0;D1;+0:1])-[Cl;H0;D1;+0:2].O=[c;H0;D3;+0:3]1:[nH;D2;+0:4]:[c:5]:[#7;a:6]:[c:7](:[c:8]):[c:9]:1:[c:10]>>[Cl;H0;D1;+0:2]-[c;H0;D3;+0:3]1:[n;H0;D2;+0:4]:[c:5]:[#7;a:6]:[c:7](:[c:8]):[c:9]:1:[c:10].[ClH;D0;+0:1]
null
[]
null
null
null
null
A mixture of 6-methoxy-7-(2-piperidinoethoxy)-3,4-dihydroquinazolin-4-one (440 mg, 1.45 mmol), thionyl chloride (15 ml) and DMF (3 drops) was heated at reflux for 3 hours then allowed to cool. The excess thionyl chloride was removed by evaporation and the residue was azeotroped with toluene to give a crude 4-chloro-6-m...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1CC[NH]CC1
Other
CN(C)C=O
null
null
COc1cc2c(=O)[nH]cnc2cc1OCCN1CCCCC1.O=S(Cl)Cl>CN(C)C=O>COc1cc2c(Cl)ncnc2cc1OCCN1CCCCC1.Cl
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3ea6bc0fd8994e49ab3fba60f5e7f91b
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1cnc2[nH]ccc2c1>>COc1cc2c(Oc3cnc4[nH]ccc4c3)ncnc2cc1OCCCN1CCCC1
[OH-].[Na+].ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1.OC=1C=C2C(=NC1)NC=C2.C([O-])([O-])=O.[K+].[K+]>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCC1)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]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:15]4[cH:1...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1cnc2[nH]ccc2c1
COc1cc2c(Oc3cnc4[nH]ccc4c3)ncnc2cc1OCCCN1CCCC1
null
null
ClCCl.CO.CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2cnc3[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].[#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]
18
[{"value": 18.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCC1)OC=1C=C2C(=NC1)NC=C2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 17.5, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCCC1)OC=1C=C2C(=NC1)NC=C2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
95
CELSIUS
6
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), 5-hydroxy-1H-pyrrolo[2,3-b]pyridine (100 mg, 0.75 mmol) and potassium carbonate (280 mg, 2.0 mmol) in DMF (4 ml) was stirred at 95° C. for 6 hours and allowed to...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1cnc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]C1
HCl
ClCCl.CO.CN(C)C=O
95
6
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1cnc2[nH]ccc2c1>ClCCl.CO.CN(C)C=O>COc1cc2c(Oc3cnc4[nH]ccc4c3)ncnc2cc1OCCCN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d1fd4ad30bad489e975d720d33a26162
COc1cnc2[nH]ccc2c1>>Oc1cnc2[nH]ccc2c1
[OH-].[Na+].B(Br)(Br)Br.COC=1C=C2C(=NC1)NC=C2>>OC=1C=C2C(=NC1)NC=C2
C[O:1][c:2]1[cH:3][n:4][c:5]2[nH:6][cH:7][cH:8][c:9]2[cH:10]1>>[OH:1][c:2]1[cH:3][n:4][c:5]2[nH:6][cH:7][cH:8][c:9]2[cH:10]1
COc1cnc2[nH]ccc2c1
Oc1cnc2[nH]ccc2c1
null
null
ClCCl.O
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1cnc2[nH]ccc2c1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]:[#7;a:5]:[c:6]:[#7;a:7]>>[#7;a:7]:[c:6]:[#7;a:5]:[c:4]:[c:2](-[OH;D1;+0:1]):[c:3]
57
[{"value": 57.0, "product": "OC=1C=C2C(=NC1)NC=C2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 56.7, "product": "OC=1C=C2C(=NC1)NC=C2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A suspension of 5-methoxy-1H-pyrrolo[2,3-b]pyridine (210 mg, 1.42 mmol), (Heterocycles 50, (2), 1065–1080, (1999)), in dichloromethane (10 ml) was stirred in an inert atmosphere, a 1.0M solution of boron tribromide in dichloromethane (4.3 ml, 4.3 mmol) added dropwise and the mixture stirred at ambient temperature overn...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1cnc2[nH]ccc2c1
Other
ClCCl.O
null
null
COc1cnc2[nH]ccc2c1>ClCCl.O>Oc1cnc2[nH]ccc2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-4ac2b6b888ce48e0b972662119896213
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.O=C(O)c1cc2cc(O)ccc2[nH]1>>COc1cc2c(Oc3ccc4[nH]c(C(=O)O)cc4c3)ncnc2cc1OCCCN1CCCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1.C([O-])([O-])=O.[K+].[K+].OC=1C=C2C=C(NC2=CC1)C(=O)O>>C(=O)(O)C=1NC2=CC=C(C=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: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:21][n:20]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][c:13]([C:14](=[O:15])[OH:16])[cH:17][c:18]2[cH:19]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.O=C(O)c1cc2cc(O)ccc2[nH]1
COc1cc2c(Oc3ccc4[nH]c(C(=O)O)cc4c3)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]
36
[{"value": 36.0, "product": "C(=O)(O)C=1NC2=CC=C(C=C2C1)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 35.7, "product": "C(=O)(O)C=1NC2=CC=C(C=C2C1)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
3
HOUR
A mixture of 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (168 mg, 0.5 mmol), (prepared as described for the starting material in Example 67), potassium carbonate (345 mg, 5.0 mmol), 5-hydroxy-2-indolecarboxylic acid (106 mg, 0.6 mmol) and DMA (2.0 ml) was purged with nitrogen for 5 minutes at 25° C. This mixt...
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
100
3
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.O=C(O)c1cc2cc(O)ccc2[nH]1>CC(=O)N(C)C>COc1cc2c(Oc3ccc4[nH]c(C(=O)O)cc4c3)ncnc2cc1OCCCN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-1fbb2e166abe4a4db5cbd7ef9f602cf1
COc1cc2c(Cl)ncnc2cc1OCCCS(C)(=O)=O.Oc1ccc2cccnc2c1>>COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCCCS(C)(=O)=O
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCS(=O)(=O)C.C([O-])([O-])=O.[K+].[K+].OC1=CC=C2C=CC=NC2=C1>>COC=1C=C2C(=NC=NC2=CC1OCCCS(=O)(=O)C)OC1=CC=C2C=CC=NC2=C1
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:23]([O:24][CH2:25][CH2:26][CH2:27][S:28]([CH3:29])(=[O:30])=[O:31])[cH:22][c:21]2[n:20][cH:19][n:18]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[cH:12][cH:13][cH:14][n:15][c:16]2[cH:17]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[cH:12][cH:13][cH:14][n:15][c:16]...
COc1cc2c(Cl)ncnc2cc1OCCCS(C)(=O)=O.Oc1ccc2cccnc2c1
COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCCCS(C)(=O)=O
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1cnc2cc(Oc3ncnc4ccccc34)ccc2c1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#7;a:9]:[c:10]:[c:11]:[c:12](-[OH;D1;+0:13]):[c:14]>>[#7;a:9]:[c:10]:[c:11]:[c:12](-[O;H0;D2;+0:13]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:14]
81.4
[{"value": 81.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCS(=O)(=O)C)OC1=CC=C2C=CC=NC2=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 81.4, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCS(=O)(=O)C)OC1=CC=C2C=CC=NC2=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
90
CELSIUS
null
null
4-Chloro-6-methoxy-7-(3-methylsulphonylpropoxy)quinazoline (0.15 g, 0.45 mmol), (prepared as described for the starting material in Example 50), potassium carbonate (94 mg, 0.68 mmol) and 7-hydroxyquinoline (79 mg, 0.54 mmol) were suspended in anhydrous DMF (1.5 ml) and heated to 90° C. overnight. The compound was prec...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncccc2c1.c1ccc2ncncc2c1
HCl
CN(C)C=O
90
null
COc1cc2c(Cl)ncnc2cc1OCCCS(C)(=O)=O.Oc1ccc2cccnc2c1>CN(C)C=O>COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCCCS(C)(=O)=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-1131f735f61548db8b31112a26f39582
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Oc1ccc2nc(Cl)[nH]c2c1>>COc1cc2c(Oc3ccc4nc(Cl)[nH]c4c3)ncnc2cc1OCC1CCN(C)CC1
[Cl-].[NH4+].ClC=1NC2=C(N1)C=CC(=C2)O.[H-].[Na+].ClC=1NC2=C(N1)C=CC(=C2)O.[H-].[Na+].ClC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C>>ClC1=NC2=C(N1)C=C(C=C2)OC2=NC=NC1=CC(=C(C=C21)OC)OCC2CCN(CC2)C
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:23]([O:24][CH2:25][CH:26]3[CH2:27][CH2:28][N:29]([CH3:30])[CH2:31][CH2:32]3)[cH:22][c:21]2[n:20][cH:19][n:18]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[n:12][c:13]([Cl:14])[nH:15][c:16]2[cH:17]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[n:12][c:13]([Cl:14])[n...
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Oc1ccc2nc(Cl)[nH]c2c1
COc1cc2c(Oc3ccc4nc(Cl)[nH]c4c3)ncnc2cc1OCC1CCN(C)CC1
null
null
ClCCl.CO.CN(C)C=O.C(C)(=O)OCC
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3nc[nH]c3c2)c2ccc(OCC3CCNCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#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]
16.3
[{"value": 16.0, "product": "ClC1=NC2=C(N1)C=C(C=C2)OC2=NC=NC1=CC(=C(C=C21)OC)OCC2CCN(CC2)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 16.3, "product": "ClC1=NC2=C(N1)C=C(C=C2)OC2=NC=NC1=CC(=C(C=C21)OC)OCC2CCN(CC2)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
1
HOUR
To a portion of 2-chloro-5-hydroxybenzimidazole (191 mg, 0.75 mmol) in DMF (3 ml) was added sodium hydride (60 mg, 1.5 mmol) under argon at ambient temperature. Ten minutes later 4-chloro-6-methoxy-7-(1-methylpiperidin-4-yl)methoxyquinazoline (200 mg, 0.62 mmol), (prepared as described for the starting material in Exam...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]cnc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
ClCCl.CO.CN(C)C=O.C(C)(=O)OCC
100
1
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Oc1ccc2nc(Cl)[nH]c2c1>ClCCl.CO.CN(C)C=O.C(C)(=O)OCC>COc1cc2c(Oc3ccc4nc(Cl)[nH]c4c3)ncnc2cc1OCC1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-bbbd1dbdf3be47caba036b8ede78a409
COc1ccc2nc(Cl)[nH]c2c1>>Oc1ccc2nc(Cl)[nH]c2c1
ClC=1NC2=C(N1)C=CC(=C2)OC.B(Br)(Br)Br>>ClC=1NC2=C(N1)C=CC(=C2)O
C[O:1][c:2]1[cH:3][cH:4][c:5]2[n:6][c:7]([Cl:8])[nH:9][c:10]2[cH:11]1>>[OH:1][c:2]1[cH:3][cH:4][c:5]2[n:6][c:7]([Cl:8])[nH:9][c:10]2[cH:11]1
COc1ccc2nc(Cl)[nH]c2c1
Oc1ccc2nc(Cl)[nH]c2c1
null
null
ClCCl
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2[nH]cnc2c1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]:[c:2](-[OH;D1;+0:1]):[c:3]
159.1
[{"value": 99.0, "product": "ClC=1NC2=C(N1)C=CC(=C2)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 159.1, "product": "ClC=1NC2=C(N1)C=CC(=C2)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
2-Chloro-5-methoxybenzimidazole (0.3 g, 1.64 mmol) was suspended in dichloromethane (20 ml) under argon followed by the addition of boron tribromide (233 ul, 2.46 mmol). The reaction mixture was stirred for 2 hours at ambient temperature. The solvent was evaporated and the resulting powder was added in portions to meth...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1ccc2[nH]cnc2c1
Other
ClCCl
null
2
COc1ccc2nc(Cl)[nH]c2c1>ClCCl>Oc1ccc2nc(Cl)[nH]c2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-bc76adc5b0bd4925b3e61eaf2710b807
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Cc1nc2ccc(O)cc2[nH]1>>COc1cc2c(Oc3ccc4nc(C)[nH]c4c3)ncnc2cc1OCC1CCN(C)CC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C.OC1=CC2=C(N=C(N2)C)C=C1>>COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C)OC=1C=CC2=C(NC(=N2)C)C1
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:23]([O:24][CH2:25][CH:26]3[CH2:27][CH2:28][N:29]([CH3:30])[CH2:31][CH2:32]3)[cH:22][c:21]2[n:20][cH:19][n:18]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[n:12][c:13]([CH3:14])[nH:15][c:16]2[cH:17]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[n:12][c:13]([CH3:14])...
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Cc1nc2ccc(O)cc2[nH]1
COc1cc2c(Oc3ccc4nc(C)[nH]c4c3)ncnc2cc1OCC1CCN(C)CC1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3nc[nH]c3c2)c2ccc(OCC3CCNCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#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]
25
[{"value": 25.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)C)OC=1C=CC2=C(NC(=N2)C)C1", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 189, 4-chloro-6-methoxy-7-(1-methylpiperidin-4-yl)methoxyquinazoline, (prepared as described for the starting material in Example 10); was reacted with 5-hydroxy-2-methylbenzimidazole (200 mg, 0.62 mmol) and after work-up and purification on a 10 g silica ISOLUT...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]cnc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
null
null
null
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Cc1nc2ccc(O)cc2[nH]1>>COc1cc2c(Oc3ccc4nc(C)[nH]c4c3)ncnc2cc1OCC1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-41d9e16042814ca791d6477877ee112e
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.N#Cc1cnc2cc(O)ccc2c1>>COc1cc2c(Oc3ccc4cc(C#N)cnc4c3)ncnc2cc1OCC1CCN(C)CC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C.C(#N)C=1C=NC2=CC(=CC=C2C1)O.C([O-])([O-])=O.[K+].[K+]>>C(#N)C=1C=NC2=CC(=CC=C2C1)OC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:25]([O:26][CH2:27][CH:28]3[CH2:29][CH2:30][N:31]([CH3:32])[CH2:33][CH2:34]3)[cH:24][c:23]2[n:22][cH:21][n:20]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[cH:12][c:13]([C:14]#[N:15])[cH:16][n:17][c:18]2[cH:19]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[cH:12][c:...
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.N#Cc1cnc2cc(O)ccc2c1
COc1cc2c(Oc3ccc4cc(C#N)cnc4c3)ncnc2cc1OCC1CCN(C)CC1
null
null
ClCCl.CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1cnc2cc(Oc3ncnc4cc(OCC5CCNCC5)ccc34)ccc2c1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[#7;a:9]:[c:10]:[c:11]:[c:12](-[OH;D1;+0:13]):[c:14]>>[#7;a:9]:[c:10]:[c:11]:[c:12](-[O;H0;D2;+0:13]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:14]
86.4
[{"value": 86.0, "product": "C(#N)C=1C=NC2=CC(=CC=C2C1)OC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 86.4, "product": "C(#N)C=1C=NC2=CC(=CC=C2C1)OC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
95
CELSIUS
null
null
4-Chloro-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazoline (200 mg, 0.62 mmol), (prepared as described for the starting material in Example 10), was suspended in DMF (3 ml) under argon. 3-Cyano-7-hydroxyquinoline (116 mg, 0.68 mmol) and potassium carbonate (129 mg, 0.93 mmol) were added and the reaction mixture ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
ClCCl.CN(C)C=O
95
null
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.N#Cc1cnc2cc(O)ccc2c1>ClCCl.CN(C)C=O>COc1cc2c(Oc3ccc4cc(C#N)cnc4c3)ncnc2cc1OCC1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-07f135c27d114ba88260201d5ae6735d
CCOC(=O)c1c[nH]c2cc(OC)ccc2c1=O.O=P(Cl)(Cl)Cl>>CCOC(=O)c1cnc2cc(OC)ccc2c1Cl
P(=O)(Cl)(Cl)Cl.COC1=CC=C2C(C(=CNC2=C1)C(=O)OCC)=O>>ClC1=C(C=NC2=CC(=CC=C12)OC)C(=O)OCC
O=[c:17]1[c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[cH:7][nH:8][c:9]2[cH:10][c:11]([O:12][CH3:13])[cH:14][cH:15][c:16]21.O=P(Cl)(Cl)[Cl:18]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][n:8][c:9]2[cH:10][c:11]([O:12][CH3:13])[cH:14][cH:15][c:16]2[c:17]1[Cl:18]
CCOC(=O)c1c[nH]c2cc(OC)ccc2c1=O.O=P(Cl)(Cl)Cl
CCOC(=O)c1cnc2cc(OC)ccc2c1Cl
null
null
null
Functional Group Interconversion
OtherReaction
cc4352f89fc20313a06e82f7021393e5d431acffd8627b85ca094d4e9dc6ea22
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccc2ncccc2c1
Cl-P(-Cl)(=O)-[Cl;H0;D1;+0:1].O=[c;H0;D3;+0:2]1:[c:3](:[c:4]):[c:5](:[c:6]):[nH;D2;+0:7]:[c:8]:[c:9]:1-[C:10](=[O;D1;H0:11])-[#8:12]-[C:13]>>[C:13]-[#8:12]-[C:10](=[O;D1;H0:11])-[c:9]1:[c:8]:[n;H0;D2;+0:7]:[c:5](:[c:6]):[c:3](:[c:4]):[c;H0;D3;+0:2]:1-[Cl;H0;D1;+0:1]
73
[{"value": 73.0, "product": "ClC1=C(C=NC2=CC(=CC=C12)OC)C(=O)OCC", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Phosphorus oxychloride (88 ml) was added to ethyl 7-methoxy-4-oxo-1,4-dihydroquinoline-3-carboxylate (58 g, 235 mmol) and the mixture was heated at reflux for 45 minutes under anhydrous conditions. Upon cooling to ambient temperature, phosphorus oxychloride was evaporated and the solid residue was added in portions to ...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1cc2ccccc2nc1
c1ccc2ncccc2c1
c1ccc2ncccc2c1
HCl
null
null
null
CCOC(=O)c1c[nH]c2cc(OC)ccc2c1=O.O=P(Cl)(Cl)Cl>>CCOC(=O)c1cnc2cc(OC)ccc2c1Cl
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-9ba942eb8037492287f433c1fa78f7e6
CCOC(=O)c1cnc2cc(OC)ccc2c1Cl>>CCOC(=O)c1cnc2cc(OC)ccc2c1
ClC1=C(C=NC2=CC(=CC=C12)OC)C(=O)OCC>>C(C)OC(=O)C=1C=NC2=CC(=CC=C2C1)OC
Cl[c:17]1[c:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[cH:7][n:8][c:9]2[cH:10][c:11]([O:12][CH3:13])[cH:14][cH:15][c:16]21>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][n:8][c:9]2[cH:10][c:11]([O:12][CH3:13])[cH:14][cH:15][c:16]2[cH:17]1
CCOC(=O)c1cnc2cc(OC)ccc2c1Cl
CCOC(=O)c1cnc2cc(OC)ccc2c1
null
[Pd]
C(C)(=O)O
Functional Group Interconversion
Aromatic dehalogenation
9d8b09641537c9b7067a6060cf65ecd110c7af466a7b229ce3601533f966554e
56de34d4a44cb25d9380269ee5e138b0f24b40a3a0db22c5508049dc775a861f
c1ccc2ncccc2c1
Cl-[c;H0;D3;+0:1]1:[c:2](:[c:3]):[c:4](:[c:5]):[#7;a:6]:[c:7]:[c:8]:1-[C:9](=[O;D1;H0:10])-[#8:11]-[C:12]>>[C:12]-[#8:11]-[C:9](=[O;D1;H0:10])-[c:8]1:[c:7]:[#7;a:6]:[c:4](:[c:5]):[c:2](:[c:3]):[cH;D2;+0:1]:1
88.1
[{"value": 88.0, "product": "C(C)OC(=O)C=1C=NC2=CC(=CC=C2C1)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 88.1, "product": "C(C)OC(=O)C=1C=NC2=CC(=CC=C2C1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
4-Chloro-3-ethoxycarbonyl-7-methoxyquinoline (43 g, 162 mmol) was dissolved in acetic acid (250 ml), with 10% palladium on charcoal (1.5 g) and hydrogenated at atmospheric pressure during 8 hours. The catalyst was removed by filtration over a pad of celite and the solvent evaporated. The residue was diluted with water ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
null
c1ccc2ncccc2c1
c1ccc2ncccc2c1
c1ccc2ncccc2c1
Other
[Pd].C(C)(=O)O
null
null
CCOC(=O)c1cnc2cc(OC)ccc2c1Cl>[Pd].C(C)(=O)O>CCOC(=O)c1cnc2cc(OC)ccc2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d15a52796345473fb1230ff9d45ea3ac
CCOC(=O)c1cnc2cc(OC)ccc2c1.N>>COc1ccc2cc(C(N)=O)cnc2c1
C(C)OC(=O)C=1C=NC2=CC(=CC=C2C1)OC.N>>C(N)(=O)C=1C=NC2=CC(=CC=C2C1)OC
CCO[C:9]([c:8]1[cH:7][c:6]2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:15][c:14]2[n:13][cH:12]1)=[O:11].[NH3:10]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[cH:7][c:8]([C:9]([NH2:10])=[O:11])[cH:12][n:13][c:14]2[cH:15]1
CCOC(=O)c1cnc2cc(OC)ccc2c1.N
COc1ccc2cc(C(N)=O)cnc2c1
null
null
CO
Acylation
OtherReaction
d5b10d4f469e7a196a3b04a6a9e159a7d90514b6df5b50c1197d4b1b774c04e1
adc0ef6f6c1340dd2dbab737c85bf17fc842769181c5db1a2b4f82b391b28f9f
c1ccc2ncccc2c1
C-C-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]:[#7;a:6]:[c:7].[NH3;D0;+0:8]>>[NH2;D1;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]:[#7;a:6]:[c:7]
86
[{"value": 86.0, "product": "C(N)(=O)C=1C=NC2=CC(=CC=C2C1)OC", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
3-Ethoxycarbonyl-7-methoxyquinoline (28 g, 120 mmol) was added to a methanol solution saturated with ammonia. The suspension was stirred at ambient temperature in a glass pressure vessel for 2 weeks. The white solid was collected by filtration, washed with methanol and dried under vacuum to give 3-carbamoyl-7-methoxyqu...
10.6084/m9.figshare.5104873.v1
null
Ester
Primary amide
null
null
c1ccc2ncccc2c1
HO-
CO
null
null
CCOC(=O)c1cnc2cc(OC)ccc2c1.N>CO>COc1ccc2cc(C(N)=O)cnc2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-0d77e5cc83ad471fa04f88e630a77a28
COc1ccc2cc(C#N)cnc2c1>>N#Cc1cnc2cc(O)ccc2c1
C(#N)C=1C=NC2=CC(=CC=C2C1)OC.[Cl-].[Cl-].[Cl-].[Al+3].[Cl-].[Cl-].[Cl-].[Al+3]>>C(#N)C=1C=NC2=CC(=CC=C2C1)O
C[O:9][c:8]1[cH:7][c:6]2[n:5][cH:4][c:3]([C:2]#[N:1])[cH:13][c:12]2[cH:11][cH:10]1>>[N:1]#[C:2][c:3]1[cH:4][n:5][c:6]2[cH:7][c:8]([OH:9])[cH:10][cH:11][c:12]2[cH:13]1
COc1ccc2cc(C#N)cnc2c1
N#Cc1cnc2cc(O)ccc2c1
null
null
C1=CC=CC=C1
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2ncccc2c1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]:[c:5]:[#7;a:6]>>[#7;a:6]:[c:5]:[c:4]:[c:2](-[OH;D1;+0:1]):[c:3]
68
[{"value": 68.0, "product": "C(#N)C=1C=NC2=CC(=CC=C2C1)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 66.6, "product": "C(#N)C=1C=NC2=CC(=CC=C2C1)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
3-Cyano-7-methoxyquinoline (380 mg, 2.1 mmol) was suspended in benzene (10 ml), aluminium trichloride (826 mg, 6.2 mmol) was added and the mixture heated at reflux for 30 minutes. More aluminium trichloride (275 mg, 2.1 mmol) was added and the mixture refluxed for a further 2 hours. The solvent was evaporated, the dark...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1ccc2ncccc2c1
Other
C1=CC=CC=C1
null
1
COc1ccc2cc(C#N)cnc2c1>C1=CC=CC=C1>N#Cc1cnc2cc(O)ccc2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-fda18e06f8a245eea32abe311f47265c
COc1cc2c(Oc3ccc4c(c3)CCCN4C(=O)OC(C)(C)C)ncnc2cc1OCCCN1CCOCC1>>COc1cc2c(Oc3ccc4c(c3)CCCN4)ncnc2cc1OCCCN1CCOCC1
COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)OC=1C=C2CCCN(C2=CC1)C(=O)OC(C)(C)C.C(=O)(C(F)(F)F)O>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)OC=1C=C2CCCNC2=CC1
CC(C)(C)OC(=O)[N:17]1[c:11]2[cH:10][cH:9][c:8]([O:7][c:6]3[c:5]4[cH:4][c:3]([O:2][CH3:1])[c:23]([O:24][CH2:25][CH2:26][CH2:27][N:28]5[CH2:29][CH2:30][O:31][CH2:32][CH2:33]5)[cH:22][c:21]4[n:20][cH:19][n:18]3)[cH:13][c:12]2[CH2:14][CH2:15][CH2:16]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[c:1...
COc1cc2c(Oc3ccc4c(c3)CCCN4C(=O)OC(C)(C)C)ncnc2cc1OCCCN1CCOCC1
COc1cc2c(Oc3ccc4c(c3)CCCN4)ncnc2cc1OCCCN1CCOCC1
null
null
ClCCl
Reduction
Boc amine deprotection
63a5111cf3995bded3c99cc3b367a6b550d62d47f4aaa59e59daddf6b3bfb17f
a94b29c7264c852156fc1cdd4a0951a4fc26c06d0edc9e50c743825dbf79e3fd
c1nc(Oc2ccc3c(c2)CCCN3)c2ccc(OCCCN3CCOCC3)cc2n1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1](-[C:2]-[C:3])-[c:4](:[c:5]):[c:6]>>[C:3]-[C:2]-[NH;D2;+0:1]-[c:4](:[c:5]):[c:6]
93.2
[{"value": 93.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)OC=1C=C2CCCNC2=CC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 93.2, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)OC=1C=C2CCCNC2=CC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
To 6-methoxy-7-(3-morpholinopropoxy)-4-((1-tertbutoxycarbonyl-1,2,3,4-tetrahydroquinolin-6-yl)oxy)quinazoline (110 mg, 0.2 mmol) in solution in dichloromethane (3 ml) was added TFA (0.3 ml) and the mixture stirred for 1 hour at ambient temperature. The solvents were evaporated and the remaining oil was diluted with dic...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
c1ccc2c(c1)CCC[NH]2
c1ccc2c(c1)CCCN2
c1ccc2c(c1)CCCN2.c1ccc2ncncc2c1.C1COCC[NH]1
HO-
ClCCl
null
1
COc1cc2c(Oc3ccc4c(c3)CCCN4C(=O)OC(C)(C)C)ncnc2cc1OCCCN1CCOCC1>ClCCl>COc1cc2c(Oc3ccc4c(c3)CCCN4)ncnc2cc1OCCCN1CCOCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3cc2a4e687ea4f5dbc359a8d76ea9b1e
CC(C)(C)OC(=O)N1CCCc2ccccc21.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1>>COc1cc2c(Oc3ccc4c(c3)CCCN4C(=O)OC(C)(C)C)ncnc2cc1OCCCN1CCOCC1
[H-].[Na+].C(C)(C)(C)OC(=O)N1CCCC2=CC=CC=C12.C([O-])([O-])=O.[K+].[K+].ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCOCC1>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)OC=1C=C2CCCN(C2=CC1)C(=O)OC(C)(C)C
[cH:8]1[cH:9][cH:10][c:11]2[c:12]([cH:13]1)[CH2:14][CH2:15][CH2:16][N:17]2[C:18](=[O:19])[O:20][C:21]([CH3:22])([CH3:23])[CH3:24].Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:30]([O:31][CH2:32][CH2:33][CH2:34][N:35]3[CH2:36][CH2:37][O:38][CH2:39][CH2:40]3)[cH:29][c:28]2[n:27][cH:26][n:25]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[...
CC(C)(C)OC(=O)N1CCCc2ccccc21.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1
COc1cc2c(Oc3ccc4c(c3)CCCN4C(=O)OC(C)(C)C)ncnc2cc1OCCCN1CCOCC1
null
null
O.CN(C=O)C.C(C)(=O)OCC
Heteroatom Alkylation and Arylation
OtherReaction
d1e86c021d9691a031f3e2141033c42b687d8c898d5b5a9f7608064ec8f667d6
51fd03eb6a688046e417b9ed09ea0e72062396d005af1318b9b5f376a97da959
c1nc(Oc2ccc3c(c2)CCCN3)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].[c:9]:[c:10]:[cH;D2;+0:11]:[c:12]:[c:13]>>[c:9]:[c:10]:[c;H0;D3;+0:11](-[#8:14]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]:[c:13]
71
[{"value": 71.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)OC=1C=C2CCCN(C2=CC1)C(=O)OC(C)(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 70.5, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)OC=1C=C2CCCN(C2=CC1)C(=O)OC(C)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
120
CELSIUS
2
HOUR
6-Hydroxy-4-(1-tertbutoxycarbonyl-1,2,3,4-tetrahydroquinoline (82 mg, 0.32 mmol) was dissolved in anhydrous dimethylformamide under argon, with potassium carbonate (61 mg, 0.44 mmol) and 4-chloro-6-methoxy-7-(3-morpholinopropoxy)quinazoline (100 mg, 0.3m mmol), (prepared as described for the starting material in Exampl...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
Ether
c1ccc2c(c1)CCC[NH]2.c1ccc2ncncc2c1
c1ccc2c(c1)CCC[NH]2.c1ccc2ncncc2c1
c1ccc2c(c1)CCC[NH]2.c1ccc2ncncc2c1.C1COCC[NH]1
null
O.CN(C=O)C.C(C)(=O)OCC
120
2
CC(C)(C)OC(=O)N1CCCc2ccccc21.COc1cc2c(Cl)ncnc2cc1OCCCN1CCOCC1>O.CN(C=O)C.C(C)(=O)OCC>COc1cc2c(Oc3ccc4c(c3)CCCN4C(=O)OC(C)(C)C)ncnc2cc1OCCCN1CCOCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3489e772959c456aaf5a183afd3c8cc5
Oc1ccc2[nH]ccc2c1>>Oc1ccc2c(c1)CCN2
OC=1C=C2C=CNC2=CC1.C(#N)[BH3-].[Na+].B(F)(F)F.CCOCC>>OC=1C=C2CCNC2=CC1
[OH:1][c:2]1[cH:3][cH:4][c:5]2[c:6]([cH:7]1)[cH:8][cH:9][nH:10]2>>[OH:1][c:2]1[cH:3][cH:4][c:5]2[c:6]([cH:7]1)[CH2:8][CH2:9][NH:10]2
Oc1ccc2[nH]ccc2c1
Oc1ccc2c(c1)CCN2
null
null
CO
Reduction
OtherReaction
d7c64ff5bdeff25897e9ebfc8baf5f34c2f69037fd4e91a3394e3e20a554de0e
2b7f370a519e29b4dede190aa36b37f30822496e32f2c8bfa9736e631bde52e2
c1ccc2c(c1)CCN2
[c:1]:[c:2]1:[nH;D2;+0:3]:[cH;D2;+0:4]:[cH;D2;+0:5]:[c:6]:1:[c:7]>>[c:1]:[c:2]1:[c:6](:[c:7])-[CH2;D2;+0:5]-[CH2;D2;+0:4]-[NH;D2;+0:3]-1
73
[{"value": 73.0, "product": "OC=1C=C2CCNC2=CC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 71.5, "product": "OC=1C=C2CCNC2=CC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
5-Hydroxyindole (2 g, 15 mmol) was dissolved in methanol (60 ml) under argon. Sodium cyanoborohydride (1.89 g, 30 mmol) and trifluoroboron etherate (4.2 ml, 33 mmol) were added and the mixture was heated at reflux for 3 hours then left to cool to ambient temperature. The solvent was evaporated and the residue was parti...
10.6084/m9.figshare.5104873.v1
null
null
Secondary amine
c1ccc2[nH]ccc2c1
c1ccc2c(c1)CCN2
c1ccc2c(c1)CCN2
null
CO
null
null
Oc1ccc2[nH]ccc2c1>CO>Oc1ccc2c(c1)CCN2
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-158a12b79f5b44e38fc23b2c74c8bc3c
COc1cc2c(Cl)ncnc2cc1OCCN1CCCCC1.Oc1ccc2cccnc2c1>>COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCCN1CCCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCN1CCCCC1.C([O-])([O-])=O.[K+].[K+].OC1=CC=C2C=CC=NC2=C1.[OH-].[Na+]>>COC=1C=C2C(=NC=NC2=CC1OCCN1CCCCC1)OC1=CC=C2C=CC=NC2=C1
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:23]([O:24][CH2:25][CH2:26][N:27]3[CH2:28][CH2:29][CH2:30][CH2:31][CH2:32]3)[cH:22][c:21]2[n:20][cH:19][n:18]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[cH:12][cH:13][cH:14][n:15][c:16]2[cH:17]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[cH:12][cH:13][cH:14][n:1...
COc1cc2c(Cl)ncnc2cc1OCCN1CCCCC1.Oc1ccc2cccnc2c1
COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCCN1CCCCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1cnc2cc(Oc3ncnc4cc(OCCN5CCCCC5)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]
75
[{"value": 75.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCN1CCCCC1)OC1=CC=C2C=CC=NC2=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 74.4, "product": "COC=1C=C2C(=NC=NC2=CC1OCCN1CCCCC1)OC1=CC=C2C=CC=NC2=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a suspension of 4-chloro-6-methoxy-7-(2-piperidinoethoxy)quinazoline (250 mg, 0.78 mmol), (prepared as described for the starting material in Example 180), in DMF (10 ml) was added anhydrous potassium carbonate (320 mg, 2.30 mmol) and 7-hydroxyquinoline (135 mg, 0.94 mmol), and the reaction heated under reflux at 90...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
CN(C)C=O
null
null
COc1cc2c(Cl)ncnc2cc1OCCN1CCCCC1.Oc1ccc2cccnc2c1>CN(C)C=O>COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCCN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b2c124acdf06481b890ccc98250d1680
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Oc1ccc2cccnc2c1>>COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCc1ccccc1
C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)Cl)OC.C([O-])([O-])=O.[K+].[K+].OC1=CC=C2C=CC=NC2=C1.[OH-].[Na+]>>C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC1=CC=C2C=CC=NC2=C1)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[cH:12][cH:13][cH:14][n:15][c:16]2[cH:17]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[cH:12][cH:13][cH:14][n:15][c:16]4[cH:...
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Oc1ccc2cccnc2c1
COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCc1ccccc1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1ccc(COc2ccc3c(Oc4ccc5cccnc5c4)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].[#7;a:9]:[c:10]:[c:11]:[c:12](-[OH;D1;+0:13]):[c:14]>>[#7;a:9]:[c:10]:[c:11]:[c:12](-[O;H0;D2;+0:13]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:14]
60.7
[{"value": 60.0, "product": "C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC1=CC=C2C=CC=NC2=C1)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 60.7, "product": "C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC1=CC=C2C=CC=NC2=C1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a suspension of 7-benzyloxy-4-chloro-6-methoxyquinazoline (1.82 g, 6.1 mmol), (prepared as described for the starting material in Example 1), in DMF (50 ml) was added potassium carbonate (2.50 g, 18.1 mmol) and 7-hydroxyquinoline (1.06 g, 7.3 mmol), and the reaction heated under reflux at 90C for 4 hours. The reacti...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncccc2c1.c1ccc2ncncc2c1.c1ccccc1
HCl
CN(C)C=O
null
null
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Oc1ccc2cccnc2c1>CN(C)C=O>COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCc1ccccc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-5fcd951e2bcd4620b62c72f848929a18
COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCc1ccccc1>>COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1O
C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)OC1=CC=C2C=CC=NC2=C1)OC>>OC1=C(C=C2C(=NC=NC2=C1)OC1=CC=C2C=CC=NC2=C1)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[cH:12][cH:13][cH:14][n: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[cH:12][cH:13][cH:14][n:15][c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22][c:23]...
COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCc1ccccc1
COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1O
null
null
FC(C(=O)O)(F)F
Deprotection
Hydroxyl benzyl deprotection
36869d1fe85185a14d9eb30bf05178c600a9b6eca277ffaf3803578c30e0bf5d
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1cnc2cc(Oc3ncnc4ccccc34)ccc2c1
[#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]
76.2
[{"value": 76.0, "product": "OC1=C(C=C2C(=NC=NC2=C1)OC1=CC=C2C=CC=NC2=C1)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 76.2, "product": "OC1=C(C=C2C(=NC=NC2=C1)OC1=CC=C2C=CC=NC2=C1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 7-benzyloxy-6-methoxy-4-(quinolin-7-yloxy)quinazoline (1.50 g, 3.70 mmol), (prepared as described in Example 196), in trifluoroacetic acid (50 ml) was heated at reflux for 150 minutes. The reaction was concentrated in vacuo and the reaction neutralised with saturated aqueous ammonium hydroxide. The result...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
c1ccccc1
null
c1ccc2ncccc2c1.c1ccc2ncncc2c1
Other
FC(C(=O)O)(F)F
null
null
COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCc1ccccc1>FC(C(=O)O)(F)F>COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-f583c55c70a04babaa0b691d44c7be83
COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1O.OCCN1CCOCC1>>COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCCN1CCOCC1
OC1=C(C=C2C(=NC=NC2=C1)OC1=CC=C2C=CC=NC2=C1)OC.C([O-])([O-])=O.[K+].[K+].OCCN1CCOCC1>>COC=1C=C2C(=NC=NC2=CC1OCCN1CCOCC1)OC1=CC=C2C=CC=NC2=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[cH:12][cH:13][cH:14][n:15][c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[OH:24].O[CH2:25][CH2:26][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[cH:12][cH:13][cH:14][n:15][c:...
COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1O.OCCN1CCOCC1
COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCCN1CCOCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1cnc2cc(Oc3ncnc4cc(OCCN5CCOCC5)ccc34)ccc2c1
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]
71.4
[{"value": 71.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCN1CCOCC1)OC1=CC=C2C=CC=NC2=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 71.4, "product": "COC=1C=C2C(=NC=NC2=CC1OCCN1CCOCC1)OC1=CC=C2C=CC=NC2=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a suspension of 7-hydroxy-6-methoxy-4-(quinolin-7-yloxy)quinazoline (450 mg, 1.40 mmol), (prepared as described in Example 197), in DMF (50 ml) was added anhydrous potassium carbonate (773 mg, 5.60 mmol) and 4-(2-hydroxyethyl)morpholine (335 mg, 1.80 mmol), and the reaction heated under reflux for 2 hours. The DMF w...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccc2ncccc2c1.c1ccc2ncncc2c1.C1COCC[NH]1
HO-
CN(C)C=O
null
null
COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1O.OCCN1CCOCC1>CN(C)C=O>COc1cc2c(Oc3ccc4cccnc4c3)ncnc2cc1OCCN1CCOCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-08221d9b796a49a8a40abe09d42df29c
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1ccc2c(c1)[nH]c1ccccc12>>c1ccc2ncncc2c1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1.C([O-])([O-])=O.[K+].[K+].OC1=CC=2NC3=CC=CC=C3C2C=C1>>N1=CN=CC2=CC=CC=C12
COc1c[c:9]2[c:4]([cH:3]c1OCCCN1CCCC1)[n:5][cH:6][n:7][c:8]2Cl.Oc1ccc2c(c1)[nH]c1c2c[cH:2][cH:1][cH:10]1>>[cH:1]1[cH:2][cH:3][c:4]2[n:5][cH:6][n:7][cH:8][c:9]2[cH:10]1
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1ccc2c(c1)[nH]c1ccccc12
c1ccc2ncncc2c1
null
null
CN(C)C=O
Miscellaneous
OtherReaction
eea6960b165e3bf92b393c08034a1c42b74c18cdc7433f4b91dbdb50543482d2
a6c856a27352a45ad86c0cc2b6f73864c00de75080ef629d9dcc8701b1adc73c
c1ccc2ncncc2c1
C-O-c1:c:[c;H0;D3;+0:1]2:[c:2](:[#7;a:3]:[c:4]:[#7;a:5]:[c;H0;D3;+0:6]:2-Cl):[cH;D2;+0:7]:c:1-O-C-C-C-N1-C-C-C-C-1.O-c1:c:c:c2:c(:[nH]:c3:[cH;D2;+0:8]:[c:9]:[cH;D2;+0:10]:c:c:3:2):c:1>>[#7;a:3]1:[c:4]:[#7;a:5]:[cH;D2;+0:6]:[c;H0;D3;+0:1]2:[cH;D2;+0:8]:[c:9]:[cH;D2;+0:10]:[cH;D2;+0:7]:[c:2]:1:2
76.8
[{"value": 22.0, "product": "N1=CN=CC2=CC=CC=C12", "details": "PERCENTYIELD", "is_desired": false}, {"value": 76.8, "product": "N1=CN=CC2=CC=CC=C12", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
null
null
To a solution of 4-chloro-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline (100 mg, 0.31 mmol), (prepared as described for the starting material in Example 9), in DMF (10 ml) was added potassium carbonate (124 mg, 0.9 mmol, 3eq.) followed by 2-hydroxycarbazole (66 mg, 0.36 mmol, 1.2eq.) and the reaction heated at 10...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Ether.Ether.Aromatic alcohol.Tertiary amine
null
C1CCNC1.c1ccc2ncncc2c1.c1ccc2c(c1)[nH]c1ccccc12
c1ccc2ncncc2c1
c1ccc2ncncc2c1
HCl
CN(C)C=O
100
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1ccc2c(c1)[nH]c1ccccc12>CN(C)C=O>c1ccc2ncncc2c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-01d532ea73d146a0826d5a2a83c5d8b3
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Nc1ccc2[nH]ccc2c1>>COc1cc2c(Nc3ccc4[nH]ccc4c3)ncnc2cc1OCc1ccccc1
Cl.C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)Cl)OC.NC=1C=C2C=CNC2=CC1>>Cl.C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)NC=1C=C2C=CNC2=CC1)OC
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:22]([O:23][CH2:24][c:25]3[cH:26][cH:27][cH:28][cH:29][cH:30]3)[cH:21][c:20]2[n:19][cH:18][n:17]1.[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[cH:16]3)[n:17...
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Nc1ccc2[nH]ccc2c1
COc1cc2c(Nc3ccc4[nH]ccc4c3)ncnc2cc1OCc1ccccc1
null
null
C(C)(C)O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(COc2ccc3c(Nc4ccc5[nH]ccc5c4)ncnc3c2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[NH2;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[NH;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
96
[{"value": 96.0, "product": "Cl.C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)NC=1C=C2C=CNC2=CC1)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 96.0, "product": "Cl.C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)NC=1C=C2C=CNC2=CC1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 7-benzyloxy-4-chloro-6-methoxyquinazoline (5 g, 16.6 mmol), (prepared as described for the starting material in Example 1), 5-aminoindole (2.4 g, 18.2 mmol) in isopropanol (60 ml) containing 5N hydrogen chloride in isopropanol (260 μl, 1.6 mmol) was refluxed for 90 minutes. After cooling the volatiles wer...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.c1ccccc1
HCl
C(C)(C)O
null
null
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Nc1ccc2[nH]ccc2c1>C(C)(C)O>COc1cc2c(Nc3ccc4[nH]ccc4c3)ncnc2cc1OCc1ccccc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e850a844177148f189cf982822d768bf
COc1cc2c(Nc3ccc4[nH]ccc4c3)ncnc2cc1OCc1ccccc1>>COc1cc2c(Nc3ccc4[nH]ccc4c3)ncnc2cc1O
Cl.C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)NC=1C=C2C=CNC2=CC1)OC.C(=O)[O-].[NH4+]>>OC1=C(C=C2C(=NC=NC2=C1)NC=1C=C2C=CNC2=CC1)OC
c1ccc(C[O:23][c:22]2[c:3]([O:2][CH3:1])[cH:4][c:5]3[c:6]([NH:7][c:8]4[cH:9][cH:10][c:11]5[nH:12][cH:13][cH:14][c:15]5[cH:16]4)[n:17][cH:18][n:19][c:20]3[cH:21]2)cc1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][cH:13][cH:14][c:15]4[cH:16]3)[n:17][cH:18][n:19][c:20]2[cH:21][c:22]1[OH:23]
COc1cc2c(Nc3ccc4[nH]ccc4c3)ncnc2cc1OCc1ccccc1
COc1cc2c(Nc3ccc4[nH]ccc4c3)ncnc2cc1O
null
[Pd]
CN(C)C=O.CO
Deprotection
Hydroxyl benzyl deprotection
36869d1fe85185a14d9eb30bf05178c600a9b6eca277ffaf3803578c30e0bf5d
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2c(Nc3ccc4[nH]ccc4c3)ncnc2c1
[#7;a:1]:[c:2]:[c:3]:[c:4](-[O;H0;D2;+0:5]-C-c1:c:c:c:c:c:1):[c:6]>>[#7;a:1]:[c:2]:[c:3]:[c:4](-[OH;D1;+0:5]):[c:6]
97
[{"value": 97.0, "product": "OC1=C(C=C2C(=NC=NC2=C1)NC=1C=C2C=CNC2=CC1)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 96.1, "product": "OC1=C(C=C2C(=NC=NC2=C1)NC=1C=C2C=CNC2=CC1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
A solution of give 7-benzyloxy-4-(indol-5-ylamino)-6-methoxyquinazoline hydrochloride (10 g, 23.1 mmol) in methanol (300 ml) and DMF (100 ml) containing ammonium formate (22gr, 347 mmol) and 10% palladium on charcoal (1 g) was stirred overnight at ambient temperature. The solution was filtered over celite and washed wi...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
c1ccccc1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
Other
[Pd].CN(C)C=O.CO
null
8
COc1cc2c(Nc3ccc4[nH]ccc4c3)ncnc2cc1OCc1ccccc1>[Pd].CN(C)C=O.CO>COc1cc2c(Nc3ccc4[nH]ccc4c3)ncnc2cc1O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-14091c5c560c40b28422ab56234f92cf
COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.OCCCN1CCOCC1>>COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCOCC1
N(=NC(=O)OCC)C(=O)OCC.OC1=C(C=C2C(=NC=NC2=C1)NC=1C=C2C=C(NC2=CC1)C)OC.OCCCN1CCOCC1.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1>>COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)NC=1C=C2C=C(NC2=CC1)C
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[cH:15][c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[OH:24].O[CH2:25][CH2:26][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]([NH:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH...
COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.OCCCN1CCOCC1
COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCOCC1
null
null
CN(C)C=O.C(Cl)Cl
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1nc(Nc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCOCC3)cc2n1
O-[CH2;D2;+0:1]-[C:2]-[C:3].[#7;a:4]:[c:5]:[c:6]:[c:7](-[OH;D1;+0:8]):[c:9]>>[#7;a:4]:[c:5]:[c:6]:[c:7](-[O;H0;D2;+0:8]-[CH2;D2;+0:1]-[C:2]-[C:3]):[c:9]
44
[{"value": 44.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)NC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 44.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1CCOCC1)NC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
4
CELSIUS
8
HOUR
To a solution of 7-hydroxy-6-methoxy-4-(2-methylindol-5-ylamino)quinazoline (102 mg, 0.32 mmol), 4-(3-hydroxypropyl)morpholine (70 mg, 0.48 mmol), (prepared as described for the starting material in Example 60), triphenylphosphine (168 mg, 0.64 mmol) in methylene chloride (1 ml) and DMF (0.5 ml) cooled at 4° C. was add...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1COCC[NH]1
HO-
CN(C)C=O.C(Cl)Cl
4
8
COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.OCCCN1CCOCC1>CN(C)C=O.C(Cl)Cl>COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCN1CCOCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e61ba6285aad4ead92197c8467d7a3f8
Cc1cc2cc([N+](=O)[O-])ccc2[nH]1>>Cc1cc2cc(N)ccc2[nH]1
CC=1NC2=CC=C(C=C2C1)[N+](=O)[O-].[H][H]>>NC=1C=C2C=C(NC2=CC1)C
O=[N+:7]([O-])[c:6]1[cH:5][c:4]2[cH:3][c:2]([CH3:1])[nH:11][c:10]2[cH:9][cH:8]1>>[CH3:1][c:2]1[cH:3][c:4]2[cH:5][c:6]([NH2:7])[cH:8][cH:9][c:10]2[nH:11]1
Cc1cc2cc([N+](=O)[O-])ccc2[nH]1
Cc1cc2cc(N)ccc2[nH]1
null
[Pd]
C(C)O.C1CCOC1
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccc2[nH]ccc2c1
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
99.6
[{"value": 99.6, "product": "NC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 2-methyl-5-nitroindole (1 g, 5.7 mmol) in ethanol (25 ml) and THF (25 ml) containg 10% palladium on charcoal (128 mg) was hydrogenated until uptake of hydrogen ceased. The mixture was filtered and the filtrate was evaporated to give 5-amino-2-methylindole (830 mg, quant.). Conditions: See reaction.notes.p...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccc2[nH]ccc2c1
Other
[Pd].C(C)O.C1CCOC1
null
null
Cc1cc2cc([N+](=O)[O-])ccc2[nH]1>[Pd].C(C)O.C1CCOC1>Cc1cc2cc(N)ccc2[nH]1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-70f646d849c74153943d343f766c23b5
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cc1cc2cc(N)ccc2[nH]1>>COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCc1ccccc1.Cl
C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)Cl)OC.NC=1C=C2C=C(NC2=CC1)C>>Cl.C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)NC=1C=C2C=C(NC2=CC1)C)OC
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([Cl:32])[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[O:24][CH2:25][c:26]1[cH:27][cH:28][cH:29][cH:30][cH:31]1.[NH2:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][c:13]([CH3:14])[cH:15][c:16]2[cH:17]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[cH:15]...
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cc1cc2cc(N)ccc2[nH]1
COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCc1ccccc1.Cl
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(COc2ccc3c(Nc4ccc5[nH]ccc5c4)ncnc3c2)cc1
[Cl;H0;D1;+0:1]-[c;H0;D3;+0:2]1:[#7;a:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[ClH;D0;+0:1].[c:12]:[c:11](-[NH;D2;+0:10]-[c;H0;D3;+0:2]1:[#7;a:3]:[c:4]:[#7;a:5]:[c:6](:[c:7]):[c:8]:1:[c:9]):[c:13]
98.3
[{"value": 98.3, "product": "Cl.C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)NC=1C=C2C=C(NC2=CC1)C)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described for the synthesis of the starting material in Example 201, 7-benzyloxy-4-chloro-6-methoxyquinazoline (2 g, 6.6 mmol), (prepared as described for the starting material in Example 1), was reacted with 5-amino-2-methylindole (1.07 g, 7.3 mmol) to give 7-benzyloxy-6-methoxy-4-...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.c1ccccc1
null
null
null
null
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Cc1cc2cc(N)ccc2[nH]1>>COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCc1ccccc1.Cl
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-2e43e8ff57224e7fac9a2fab2e7da5a0
COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCc1ccccc1>>COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O
Cl.C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)NC=1C=C2C=C(NC2=CC1)C)OC.C(=O)[O-].[NH4+]>>OC1=C(C=C2C(=NC=NC2=C1)NC=1C=C2C=C(NC2=CC1)C)OC
c1ccc(C[O:24][c:23]2[c:3]([O:2][CH3:1])[cH:4][c:5]3[c:6]([NH:7][c:8]4[cH:9][cH:10][c:11]5[nH:12][c:13]([CH3:14])[cH:15][c:16]5[cH:17]4)[n:18][cH:19][n:20][c:21]3[cH:22]2)cc1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH: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:2...
COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCc1ccccc1
COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O
null
null
null
Deprotection
Hydroxyl benzyl deprotection
36869d1fe85185a14d9eb30bf05178c600a9b6eca277ffaf3803578c30e0bf5d
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2c(Nc3ccc4[nH]ccc4c3)ncnc2c1
[#7;a:1]:[c:2]:[c:3]:[c:4](-[O;H0;D2;+0:5]-C-c1:c:c:c:c:c:1):[c:6]>>[#7;a:1]:[c:2]:[c:3]:[c:4](-[OH;D1;+0:5]):[c:6]
93.2
[{"value": 93.0, "product": "OC1=C(C=C2C(=NC=NC2=C1)NC=1C=C2C=C(NC2=CC1)C)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 93.2, "product": "OC1=C(C=C2C(=NC=NC2=C1)NC=1C=C2C=C(NC2=CC1)C)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described for the synthesis of the starting material in Example 201, 7-benzyloxy-6-methoxy-4-(2-methylindol-5-ylamino)quinazoline hydrochloride (2.87 g, 6.4 mmol) was reacted with ammonium formate (6 g, 9.6 mmol) to give 7-hydroxy-6-methoxy-4-(2-methylindol-5-ylamino)quinazoline (1....
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
c1ccccc1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
Other
null
null
null
COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCc1ccccc1>>COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-562f7889a51b4abcb9bf350e35249033
COc1cc2c(Nc3ccc4[nH]ccc4c3)ncnc2cc1O.OCCCn1ccnn1>>COc1cc2c(Nc3ccc4[nH]ccc4c3)ncnc2cc1OCCCn1ccnn1
OC1=C(C=C2C(=NC=NC2=C1)NC=1C=C2C=CNC2=CC1)OC.N1(N=NC=C1)CCCO>>N1C=CC2=CC(=CC=C12)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1N=NC=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[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][CH2:26][n:27]1[cH:28][cH:29][n:30][n:31]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[cH:16]3)[...
COc1cc2c(Nc3ccc4[nH]ccc4c3)ncnc2cc1O.OCCCn1ccnn1
COc1cc2c(Nc3ccc4[nH]ccc4c3)ncnc2cc1OCCCn1ccnn1
null
null
null
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1cn(CCCOc2ccc3c(Nc4ccc5[nH]ccc5c4)ncnc3c2)nn1
O-[CH2;D2;+0:1]-[C:2]-[C:3].[#7;a:4]:[c:5]:[c:6]:[c:7](-[OH;D1;+0:8]):[c:9]>>[#7;a:4]:[c:5]:[c:6]:[c:7](-[O;H0;D2;+0:8]-[CH2;D2;+0:1]-[C:2]-[C:3]):[c:9]
42.1
[{"value": 42.0, "product": "N1C=CC2=CC(=CC=C12)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1N=NC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 42.1, "product": "N1C=CC2=CC(=CC=C12)NC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1N=NC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 205, 7-hydroxy-4-(indol-5-ylamino)-6-methoxyquinazoline (98 mg, 0.32 mmol), (prepared as described for the starting material in Example 201), was reacted with 3-(1,2,3-triazol-1-yl)propan-1-ol (61 mg, 0.48 mmol) to give 4-(indol-5-ylamino)-6-methoxy-7-(3-(1,2,3-...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.c1c[nH]nn1
HO-
null
null
null
COc1cc2c(Nc3ccc4[nH]ccc4c3)ncnc2cc1O.OCCCn1ccnn1>>COc1cc2c(Nc3ccc4[nH]ccc4c3)ncnc2cc1OCCCn1ccnn1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-379137198887428285f4bb72bff62872
C=CC(=O)OCC.c1c[nH]nn1>>CCOC(=O)C(C)n1ccnn1
N1N=NC=C1.C(C=C)(=O)OCC>>N1(N=NC=C1)C(C(=O)OCC)C
[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]=[CH2:7].[nH:8]1[cH:9][cH:10][n:11][n:12]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]([CH3:7])[n:8]1[cH:9][cH:10][n:11][n:12]1
C=CC(=O)OCC.c1c[nH]nn1
CCOC(=O)C(C)n1ccnn1
null
N1=CC=CC=C1
null
Heteroatom Alkylation and Arylation
OtherReaction
3d6179ca64e6326d7e717d0f97068c57e14a418c6194f6dfbf857e3013bf810b
51fad62e29f5f77e8a2cefce7ceeba2655475fda67fa72d63935019e1a813761
c1c[nH]nn1
[#7;a:1]1:[#7;a:2]:[nH;D2;+0:3]:[c:4]:[c:5]:1.[C:6]-[#8:7]-[C:8](=[O;D1;H0:9])-[CH;D2;+0:10]=[CH2;D1;+0:11]>>[C:6]-[#8:7]-[C:8](=[O;D1;H0:9])-[CH;D3;+0:10](-[CH3;D1;+0:11])-[n;H0;D3;+0:3]1:[#7;a:2]:[#7;a:1]:[c:5]:[c:4]:1
73.2
[{"value": 73.0, "product": "N1(N=NC=C1)C(C(=O)OCC)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 73.2, "product": "N1(N=NC=C1)C(C(=O)OCC)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
90
CELSIUS
null
null
A mixture of 1,2,3-triazole (5 g, 72.4 mmol) and ethyl acrylate (7.8 ml, 72.4 mmol) containing pyridine (50 drops) was heated at 90° C. for 4 hours. After cooling, the volatiles were removed under vacuum and the residue was purified by column chromatography eluting with methylene chloride/ether to give ethyl (1H-1,2,3-...
10.6084/m9.figshare.5104873.v1
null
Ester.Vinyl
Ester
c1c[nH]nn1
c1c[nH]nn1
c1c[nH]nn1
null
N1=CC=CC=C1
90
null
C=CC(=O)OCC.c1c[nH]nn1>N1=CC=CC=C1>CCOC(=O)C(C)n1ccnn1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b9bcb2b3e3484d9183f9971b312dfb5b
CCOC(=O)C(C)n1ccnn1>>OCCCn1ccnn1
N1(N=NC=C1)C(C(=O)OCC)C.[H-].[Al+3].[Li+].[H-].[H-].[H-].C1CCOC1.C1CCOC1.[OH-].[Na+]>>N1(N=NC=C1)CCCO
CCO[C:2](=[O:1])[CH:4]([CH3:3])[n:5]1[cH:6][cH:7][n:8][n:9]1>>[OH:1][CH2:2][CH2:3][CH2:4][n:5]1[cH:6][cH:7][n:8][n:9]1
CCOC(=O)C(C)n1ccnn1
OCCCn1ccnn1
null
null
null
Miscellaneous
OtherReaction
045e3092b4d06245a655f586ed9fcaf6c102267c1323bfa84ee054f5eb72279b
6c68e56451f63eb914da47d835c80c50f16b8e098a52b924c7914bb1a69fa96c
c1c[nH]nn1
C-C-O-[C;H0;D3;+0:1](=[O;H0;D1;+0:2])-[CH;D3;+0:3](-[CH3;D1;+0:4])-[#7;a:5]1:[#7;a:6]:[#7;a:7]:[c:8]:[c:9]:1>>[OH;D1;+0:2]-[CH2;D2;+0:1]-[CH2;D2;+0:4]-[CH2;D2;+0:3]-[#7;a:5]1:[#7;a:6]:[#7;a:7]:[c:8]:[c:9]:1
92
[{"value": 92.0, "product": "N1(N=NC=C1)CCCO", "details": "PERCENTYIELD", "is_desired": false}]
0
CELSIUS
1
HOUR
A solution of ethyl (1H-1,2,3-triazol-1-yl)propanoate (8.96 g, 53 mmol) in THF (50 ml) was added dropwise to a suspension of lithium aluminium hydride (3 g, 79 mmol) in THF (250 ml) cooled at 0° C. After stirring for 1 hour at 5° C., the mixture was stirred for 1 hour at ambient temperature. The mixture was cooled at 0...
10.6084/m9.figshare.5104873.v1
null
Ester
Primary alcohol
null
null
c1c[nH]nn1
HO-
null
0
1
CCOC(=O)C(C)n1ccnn1>>OCCCn1ccnn1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-dcffef0fbd6141e2ae1123294d2ca430
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Nc1ccc2cc[nH]c2c1>>COc1cc2c(Nc3ccc4cc[nH]c4c3)ncnc2cc1OCc1ccccc1.Cl
C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)Cl)OC.NC1=CC=C2C=CNC2=C1>>Cl.C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)NC1=CC=C2C=CNC2=C1)OC
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([Cl:31])[n:17][cH:18][n:19][c:20]2[cH:21][c:22]1[O:23][CH2:24][c:25]1[cH:26][cH:27][cH:28][cH:29][cH:30]1.[NH2:7][c:8]1[cH:9][cH:10][c:11]2[cH:12][cH:13][nH:14][c:15]2[cH:16]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([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(Cl)ncnc2cc1OCc1ccccc1.Nc1ccc2cc[nH]c2c1
COc1cc2c(Nc3ccc4cc[nH]c4c3)ncnc2cc1OCc1ccccc1.Cl
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
94bd1d6b149f0eabeae34be7987089f25636bc079a6d701a568fe61e8bfdb7f3
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(COc2ccc3c(Nc4ccc5cc[nH]c5c4)ncnc3c2)cc1
[#7;a:1]:[c:2]:[c:3]:[c:4](-[NH2;D1;+0:5]):[c:6].[Cl;H0;D1;+0:7]-[c;H0;D3;+0:8]1:[#7;a:9]:[c:10]:[#7;a:11]:[c:12](:[c:13]):[c:14]:1:[c:15]>>[#7;a:1]:[c:2]:[c:3]:[c:4](-[NH;D2;+0:5]-[c;H0;D3;+0:8]1:[#7;a:9]:[c:10]:[#7;a:11]:[c:12](:[c:13]):[c:14]:1:[c:15]):[c:6].[ClH;D0;+0:7]
89
[{"value": 89.0, "product": "Cl.C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)NC1=CC=C2C=CNC2=C1)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 88.5, "product": "Cl.C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)NC1=CC=C2C=CNC2=C1)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described for the preparation of the starting material in Example 201, 7-benzyloxy-4-chloro-6-methoxyquinazoline (2.5 g, 8.3 mmol), (prepared as described for the starting material in Example 1), was reacted with 6-aminoindole (1.5 g, 11.4 mmol) to give 7-benzyloxy-4-(indol-6-ylamin...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.c1ccccc1
null
null
null
null
COc1cc2c(Cl)ncnc2cc1OCc1ccccc1.Nc1ccc2cc[nH]c2c1>>COc1cc2c(Nc3ccc4cc[nH]c4c3)ncnc2cc1OCc1ccccc1.Cl
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-23f127fb712a4282b04e1a0edbe7130f
COc1cc2c(Nc3ccc4cc[nH]c4c3)ncnc2cc1OCc1ccccc1>>COc1cc2c(Nc3ccc4cc[nH]c4c3)ncnc2cc1O
Cl.C(C1=CC=CC=C1)OC1=C(C=C2C(=NC=NC2=C1)NC1=CC=C2C=CNC2=C1)OC.C(=O)[O-].[NH4+]>>OC1=C(C=C2C(=NC=NC2=C1)NC1=CC=C2C=CNC2=C1)OC
c1ccc(C[O:23][c:22]2[c:3]([O:2][CH3:1])[cH:4][c:5]3[c:6]([NH:7][c:8]4[cH:9][cH:10][c:11]5[cH:12][cH:13][nH:14][c:15]5[cH:16]4)[n:17][cH:18][n:19][c:20]3[cH:21]2)cc1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([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]
COc1cc2c(Nc3ccc4cc[nH]c4c3)ncnc2cc1OCc1ccccc1
COc1cc2c(Nc3ccc4cc[nH]c4c3)ncnc2cc1O
null
null
null
Deprotection
Hydroxyl benzyl deprotection
36869d1fe85185a14d9eb30bf05178c600a9b6eca277ffaf3803578c30e0bf5d
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2c(Nc3ccc4cc[nH]c4c3)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]
76
[{"value": 76.0, "product": "OC1=C(C=C2C(=NC=NC2=C1)NC1=CC=C2C=CNC2=C1)OC", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described for the preparation of the starting material in Example 201, 7-benzyloxy-4-(indol-6-ylamino)-6-methoxyquinazoline hydrochloride was treated with ammonium formate (655 mg, 10.4 mmol) to give 7-hydroxy-4-(indol-6-ylamino)-6-methoxyquinazoline (162 mg, 76%). Conditions: See r...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
c1ccccc1
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1
Other
null
null
null
COc1cc2c(Nc3ccc4cc[nH]c4c3)ncnc2cc1OCc1ccccc1>>COc1cc2c(Nc3ccc4cc[nH]c4c3)ncnc2cc1O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-1a4ae1a91c574ff4aea685ef8980740d
COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.Cc1nccn1CCCO>>COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCn1ccnc1C
OC1=C(C=C2C(=NC=NC2=C1)NC=1C=C2C=C(NC2=CC1)C)OC.OCCCN1C(=NC=C1)C>>COC=1C=C2C(=NC=NC2=CC1OCCCN1C(=NC=C1)C)NC=1C=C2C=C(NC2=CC1)C
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14])[cH:15][c:16]4[cH:17]3)[n:18][cH:19][n:20][c:21]2[cH:22][c:23]1[OH:24].O[CH2:25][CH2:26][CH2:27][n:28]1[cH:29][cH:30][n:31][c:32]1[CH3:33]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][c:13]([CH3:14...
COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.Cc1nccn1CCCO
COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCn1ccnc1C
null
null
null
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1cn(CCCOc2ccc3c(Nc4ccc5[nH]ccc5c4)ncnc3c2)cn1
O-[CH2;D2;+0:1]-[C:2]-[C:3].[#7;a:4]:[c:5]:[c:6]:[c:7](-[OH;D1;+0:8]):[c:9]>>[#7;a:4]:[c:5]:[c:6]:[c:7](-[O;H0;D2;+0:8]-[CH2;D2;+0:1]-[C:2]-[C:3]):[c:9]
37.4
[{"value": 37.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1C(=NC=C1)C)NC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 37.4, "product": "COC=1C=C2C(=NC=NC2=CC1OCCCN1C(=NC=C1)C)NC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 224, 7-hydroxy-6-methoxy-4-(2-methylindol-5-ylamino)quinazoline (102 mg, 0.32 mmol), (prepared as described for the starting material in Example 205), was reacted with 1-(3-hydroxypropyl)-2-methylimidazole (67 mg, 0.48 mmol), (EP 0060696 A1), to give 6-methoxy-7...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.c1ncc[nH]1
HO-
null
null
null
COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1O.Cc1nccn1CCCO>>COc1cc2c(Nc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCCCn1ccnc1C
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-f444de9a91244262b159c3de8c35d021
COc1cc2c(Cl)ncnc2cc1OCC1CCN(CC#N)CC1.Oc1ccc2[nH]ccc2c1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC(CC#N)C1CCNCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)CC#N.OC=1C=C2C=CNC2=CC1.C([O-])([O-])=O.[Cs+].[Cs+].CN(C)C=O>>C(#N)CC(OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)C1CCNCC1
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:22]([O:23][CH2:24][CH:28]3[CH2:29][CH2:30][N:31]([CH2:25][C:26]#[N:27])[CH2:32][CH2:33]3)[cH:21][c:20]2[n:19][cH:18][n:17]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][cH:13][cH:14][c:15]2[cH:16]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[cH:9][cH:10][c:11]4[nH:12][cH:13][cH...
COc1cc2c(Cl)ncnc2cc1OCC1CCN(CC#N)CC1.Oc1ccc2[nH]ccc2c1
COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC(CC#N)C1CCNCC1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
265b3626c99bc3a4b6d8127566eafee01f77e06cc38538a2f822747cd5c1d8c5
3ca54ce149c51cfb6a830420b10afbe007cefb03af2562456f6c0f4c6be5edc1
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCC3CCNCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]:[c:7]-[#8:8]-[CH2;D2;+0:9]-[C:10]2-[C:11]-[C:12]-[N;H0;D3;+0:13](-[CH2;D2;+0:14]-[C:15]#[N;D1;H0:16])-[C:17]-[C:18]-2):[c:19]:1:[c:20].[OH;D1;+0:21]-[c:22](:[c:23]):[c:24]>>[N;D1;H0:16]#[C:15]-[CH2;D2;+0:14]-[CH;D3;+0:9](-[#8:8]-[c:7]:[c:6]:[c:5]1:[#7;a:4]:[c:3]:[...
17
[{"value": 17.0, "product": "C(#N)CC(OC1=C(C=C2C(=NC=NC2=C1)OC=1C=C2C=CNC2=CC1)OC)C1CCNCC1", "details": "PERCENTYIELD", "is_desired": false}]
90
CELSIUS
90
MINUTE
A solution of 4-chloro-6-methoxy-7-((1-cyanomethylpiperidin-4-yl)methoxy)quinazoline (200 mg, 0.58 mmol) and 5-hydroxyindole (85 mg, 0.63 mmol) in DMF (3 ml) containing cesium carbonate (282 mg, 0.86 mmol) was stirred at 90° C. for 90 minutes. After cooling, the mixture was poured onto water (25 ml). The precipitate wa...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Ether.Aromatic alcohol.Tertiary amine
Ether.Ether.Secondary amine
c1ccc2ncncc2c1.C1CC[NH]CC1
c1ccc2ncncc2c1.C1CCNCC1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CCNCC1
HCl
null
90
1.5
COc1cc2c(Cl)ncnc2cc1OCC1CCN(CC#N)CC1.Oc1ccc2[nH]ccc2c1>>COc1cc2c(Oc3ccc4[nH]ccc4c3)ncnc2cc1OC(CC#N)C1CCNCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-1fedcee2041d4060b14263b35a021e3b
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCC1CCNCC1>>CC(C)(C)C(=O)OCn1cnc2ccccc2c1=O
Cl.COC=1C=C2C(N(C=NC2=CC1OCC1CCNCC1)COC(C(C)(C)C)=O)=O.[OH-].[Na+]>>C(C(C)(C)C)(=O)OCN1C=NC2=CC=CC=C2C1=O
CO[c:15]1[c:14](OCC2CCNCC2)[cH:13][c:12]2[n:11][cH:10][n:9]([CH2:8][O:7][C:5]([C:2]([CH3:1])([CH3:3])[CH3:4])=[O:6])[c:18](=[O:19])[c:17]2[cH:16]1>>[CH3:1][C:2]([CH3:3])([CH3:4])[C:5](=[O:6])[O:7][CH2:8][n:9]1[cH:10][n:11][c:12]2[cH:13][cH:14][cH:15][cH:16][c:17]2[c:18]1=[O:19]
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCC1CCNCC1
CC(C)(C)C(=O)OCn1cnc2ccccc2c1=O
null
null
O
Reduction
OtherReaction
187ea8753b408ee833b3f50b20895b2d8ea8367a707e05bcd98a4b29794fa37f
690237014162f096d3d1f1269b75c89c1e1fd70eb0c6023c591d469905aa0575
O=c1[nH]cnc2ccccc12
C-O-[c;H0;D3;+0:1]1:[c:2]:[c:3]2:[c:4]:[#7;a:5]:[c:6]:[#7;a:7]:[c:8]:2:[c:9]:[c;H0;D3;+0:10]:1-O-C-C1-C-C-N-C-C-1>>[#7;a:7]1:[c:6]:[#7;a:5]:[c:4]:[c:3]2:[c:2]:[cH;D2;+0:1]:[cH;D2;+0:10]:[c:9]:[c:8]:1:2
132.6
[{"value": 132.6, "product": "C(C(C)(C)C)(=O)OCN1C=NC2=CC=CC=C2C1=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
null
null
To a suspension of 6-methoxy-7-(piperidin-4-ylmethoxy)-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one hydrochloride (34 g, 84 mmol), (prepared as described for the starting material in Example 12), in water cooled at 0° C. was added 1N sodium hydroxide until the mixture was at pH8. The solution was extracted with ...
10.6084/m9.figshare.5104873.v1
null
Ether.Ether.Secondary amine
null
C1CCNCC1.c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1
HO-
O
0
null
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCC1CCNCC1>O>CC(C)(C)C(=O)OCn1cnc2ccccc2c1=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3050548ff5fe46a1810a9e01baa85851
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Cc1cc2c(F)c(O)ccc2[nH]1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OCC1CCN(C)CC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(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)OCC1CCN(CC1)C)C
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:24]([O:25][CH2:26][CH:27]3[CH2:28][CH2:29][N:30]([CH3:31])[CH2:32][CH2:33]3)[cH:23][c:22]2[n:21][cH:20][n:19]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[nH:12][c:13]([CH3:14])[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][c:13]([C...
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Cc1cc2c(F)c(O)ccc2[nH]1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OCC1CCN(C)CC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCC3CCNCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
69.6
[{"value": 69.0, "product": "FC1=C2C=C(NC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 69.6, "product": "FC1=C2C=C(NC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
95
CELSIUS
2
HOUR
A solution of 4-chloro-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazoline (2 gr, 6.22 mmol), (prepared as described for the starting material in Example 10), and 4-fluoro-5-hydroxy-2-methylindole (1.23 g, 7.46 mmol) in DMF (30 ml) containing potassium carbonate (1.28 g, 9.33 mmol) was stirred at 95° C. for 2 hour...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
CN(C)C=O
95
2
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Cc1cc2c(F)c(O)ccc2[nH]1>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OCC1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3a3732b9bc3a4e508995ad8b51078eb8
COc1ccc2[nH]c(C)cc2c1F>>Cc1cc2c(F)c(O)ccc2[nH]1
FC1=C2C=C(NC2=CC=C1OC)C.B(Br)(Br)Br>>FC1=C2C=C(NC2=CC=C1O)C
C[O:8][c:7]1[c:5]([F:6])[c:4]2[cH:3][c:2]([CH3:1])[nH:12][c:11]2[cH:10][cH:9]1>>[CH3:1][c:2]1[cH:3][c:4]2[c:5]([F:6])[c:7]([OH:8])[cH:9][cH:10][c:11]2[nH:12]1
COc1ccc2[nH]c(C)cc2c1F
Cc1cc2c(F)c(O)ccc2[nH]1
null
null
C(Cl)Cl
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2[nH]ccc2c1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[OH;D1;+0:1]-[c:2](:[c:3]):[c:4]
70.7
[{"value": 70.0, "product": "FC1=C2C=C(NC2=CC=C1O)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 70.7, "product": "FC1=C2C=C(NC2=CC=C1O)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
To a solution of 4-fluoro-5-methoxy-2-methylindole (709 mg, 3.95 mmol) in methylene chloride (9 ml) cooled at −30° C. was added a solution of boron tribromide (2.18 g, 8.7 mmol) in methylene chloride (1 ml). After stirring for 1 hour at ambient temperature, the mixture was poured onto water and was diluted with methyle...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1ccc2[nH]ccc2c1
Other
C(Cl)Cl
null
1
COc1ccc2[nH]c(C)cc2c1F>C(Cl)Cl>Cc1cc2c(F)c(O)ccc2[nH]1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-eb0dcc849300485fb45634be45243899
CCOC(=O)CC(C)=O.O=[N+]([O-])c1ccc(F)c(F)c1F>>CC(=O)Cc1c([N+](=O)[O-])ccc(F)c1F
FC1=C(C(=C(C=C1)[N+](=O)[O-])F)F.C(CC(=O)C)(=O)OCC.[H-].[Na+]>>C(C)(=O)CC=1C(=C(C=CC1[N+](=O)[O-])F)F
CCOC(=O)[CH2:4][C:2]([CH3:1])=[O:3].F[c:5]1[c:6]([N+:7](=[O:8])[O-:9])[cH:10][cH:11][c:12]([F:13])[c:14]1[F:15]>>[CH3:1][C:2](=[O:3])[CH2:4][c:5]1[c:6]([N+:7](=[O:8])[O-:9])[cH:10][cH:11][c:12]([F:13])[c:14]1[F:15]
CCOC(=O)CC(C)=O.O=[N+]([O-])c1ccc(F)c(F)c1F
CC(=O)Cc1c([N+](=O)[O-])ccc(F)c1F
null
null
C1CCOC1
C-C Coupling
OtherReaction
ef592c7be4a79a025bc02d41b93309512718a06ea015c1c563159f4a93201859
22e57aa13b41a1841299f7cab78227b5ba641493069f77725888e6f7076a1586
c1ccccc1
C-C-O-C(=O)-[CH2;D2;+0:1]-[C:2](-[C;D1;H3:3])=[O;D1;H0:4].F-[c;H0;D3;+0:5](:[c:6](-[F;D1;H0:7]):[c:8]):[c:9](-[#7;+:10]):[c:11]>>[#7;+:10]-[c:9](:[c:11]):[c;H0;D3;+0:5](-[CH2;D2;+0:1]-[C:2](-[C;D1;H3:3])=[O;D1;H0:4]):[c:6](-[F;D1;H0:7]):[c:8]
72
[{"value": 72.0, "product": "C(C)(=O)CC=1C(=C(C=CC1[N+](=O)[O-])F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 72.0, "product": "C(C)(=O)CC=1C(=C(C=CC1[N+](=O)[O-])F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
5
CELSIUS
15
MINUTE
To a suspension of sodium hydride (5.42 g, 226 mmol) (prewashed with pentane) in THF (100 ml) cooled at 101C was added ethyl acetoacetate (29.4 g, 226 mmol) while keeping the temperature below 15C. After completion of addition, the mixture was further stirred for 15 minutes and cooled to 5° C. A solution of 1,2,3-trifl...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Ketone.Ester
Ketone
c1ccccc1
c1ccccc1
c1ccccc1
HF
C1CCOC1
5
0.25
CCOC(=O)CC(C)=O.O=[N+]([O-])c1ccc(F)c(F)c1F>C1CCOC1>CC(=O)Cc1c([N+](=O)[O-])ccc(F)c1F
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e34a6514760e4fefa10d12665cc4f0f4
CC(=O)Cc1c([N+](=O)[O-])ccc(F)c1F.COC(OC)OC>>COC(C)(Cc1c([N+](=O)[O-])ccc(F)c1F)OC
C(C)(=O)CC=1C(=C(C=CC1[N+](=O)[O-])F)F.O.[O-2].[O-2].[O-2].O=[Si]=O.O=[Si]=O.O=[Si]=O.O=[Si]=O.[Al+3].[Al+3].C(OC)(OC)OC.C(Cl)Cl>>FC1=C(C(=C(C=C1)[N+](=O)[O-])CC(C)(OC)OC)F
[O:2]=[C:3]([CH3:4])[CH2:5][c:6]1[c:7]([N+:8](=[O:9])[O-:10])[cH:11][cH:12][c:13]([F:14])[c:15]1[F:16].COC(O[CH3:1])[O:17][CH3:18]>>[CH3:1][O:2][C:3]([CH3:4])([CH2:5][c:6]1[c:7]([N+:8](=[O:9])[O-:10])[cH:11][cH:12][c:13]([F:14])[c:15]1[F:16])[O:17][CH3:18]
CC(=O)Cc1c([N+](=O)[O-])ccc(F)c1F.COC(OC)OC
COC(C)(Cc1c([N+](=O)[O-])ccc(F)c1F)OC
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
cb292cde20c26fa9cc02b1f65c0f8e86f6198a435483943764a6b55b68bc4551
b458ec6fb4dadeba418f2e59cf38c00d6ac6c678712484b539a4c34cee82ab7a
c1ccccc1
C-O-C(-O-[CH3;D1;+0:1])-[O;H0;D2;+0:2]-[C;D1;H3:3].[C;D1;H3:4]-[C;H0;D3;+0:5](=[O;H0;D1;+0:6])-[C:7]-[c:8]>>[C;D1;H3:3]-[O;H0;D2;+0:2]-[C;H0;D4;+0:5](-[C;D1;H3:4])(-[C:7]-[c:8])-[O;H0;D2;+0:6]-[CH3;D1;+0:1]
88
[{"value": 88.0, "product": "FC1=C(C(=C(C=C1)[N+](=O)[O-])CC(C)(OC)OC)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
24
HOUR
A solution of 3-acetylmethyl-1,2-difluoro-4-nitrobenzene (500 mg, 2.3 mmol) in methylene chloride (5 ml) containing montmorillonite K10 (1 g) and trimethyl orthoformate (5 ml) was stirred for 24 hours at ambient temperature. The solid was filtered, washed with methylene chloride and the filtrate was evaporated to give ...
10.6084/m9.figshare.5104873.v1
null
Ketone.Ether.Ether.Ether
Ether.Ether
null
null
c1ccccc1
HO-
null
null
24
CC(=O)Cc1c([N+](=O)[O-])ccc(F)c1F.COC(OC)OC>>COC(C)(Cc1c([N+](=O)[O-])ccc(F)c1F)OC
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-baab3ef98b5e4254843a1ed88ed2c7f3
COC(C)(Cc1c([N+](=O)[O-])ccc(F)c1F)OC.OCc1ccccc1>>CC(=O)Cc1c([N+](=O)[O-])ccc(OCc2ccccc2)c1F
FC1=C(C(=C(C=C1)[N+](=O)[O-])CC(C)(OC)OC)F.C(C1=CC=CC=C1)O.[H-].[Na+]>>C(C)(=O)CC=1C(=C(C=CC1[N+](=O)[O-])OCC1=CC=CC=C1)F
CO[C:2]([CH3:1])([O:3]C)[CH2:4][c:5]1[c:6]([N+:7](=[O:8])[O-:9])[cH:10][cH:11][c:12](F)[c:21]1[F:22].[OH:13][CH2:14][c:15]1[cH:16][cH:17][cH:18][cH:19][cH:20]1>>[CH3:1][C:2](=[O:3])[CH2:4][c:5]1[c:6]([N+:7](=[O:8])[O-:9])[cH:10][cH:11][c:12]([O:13][CH2:14][c:15]2[cH:16][cH:17][cH:18][cH:19][cH:20]2)[c:21]1[F:22]
COC(C)(Cc1c([N+](=O)[O-])ccc(F)c1F)OC.OCc1ccccc1
CC(=O)Cc1c([N+](=O)[O-])ccc(OCc2ccccc2)c1F
null
null
Cl.CC(=O)N(C)C
Acylation
OtherReaction
c72d3343a35fdee13c620ddc910bc8d1e5f12c9663ce0db0ad6ce5fecdd59870
12b430774bc978a28eb866af6898081d50867b776a28f71fa13b31048fc2d903
c1ccc(COc2ccccc2)cc1
C-O-[C;H0;D4;+0:1](-[C;D1;H3:2])(-[C:3]-[c:4]:[c:5](-[F;D1;H0:6]):[c;H0;D3;+0:7](-F):[c:8]:[c:9])-[O;H0;D2;+0:10]-C.[OH;D1;+0:11]-[C:12]-[c:13]>>[C;D1;H3:2]-[C;H0;D3;+0:1](=[O;H0;D1;+0:10])-[C:3]-[c:4]:[c:5](-[F;D1;H0:6]):[c;H0;D3;+0:7](-[O;H0;D2;+0:11]-[C:12]-[c:13]):[c:8]:[c:9]
56.3
[{"value": 56.0, "product": "C(C)(=O)CC=1C(=C(C=CC1[N+](=O)[O-])OCC1=CC=CC=C1)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 56.3, "product": "C(C)(=O)CC=1C(=C(C=CC1[N+](=O)[O-])OCC1=CC=CC=C1)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
To a solution of benzyl alcohol (221 mg, 2.05 mmol) in DMA (1.5 ml) was added 60% sodium hydride (82 mg, 2.05 mmol). The mixture was stirred for 1 hour at ambient temperature. A solution of 1,2-difluoro-3-(2,2-dimethoxypropyl)-4-nitrobenzene (534 mg, 2.05 mmol) in DMA (1.5 ml) was added and the mixture was stirred for ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Ether.Ether.Primary alcohol
Ketone.Ether
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HF
Cl.CC(=O)N(C)C
null
1
COC(C)(Cc1c([N+](=O)[O-])ccc(F)c1F)OC.OCc1ccccc1>Cl.CC(=O)N(C)C>CC(=O)Cc1c([N+](=O)[O-])ccc(OCc2ccccc2)c1F
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-034204feeb5942f8859af137df3fa766
CC(=O)Cc1c([N+](=O)[O-])ccc(OCc2ccccc2)c1F>>Cc1cc2c(F)c(O)ccc2[nH]1
C(C)(=O)CC=1C(=C(C=CC1[N+](=O)[O-])OCC1=CC=CC=C1)F>>FC1=C2C=C(NC2=CC=C1O)C
O=[C:2]([CH3:1])[CH2:3][c:4]1[c:5]([F:6])[c:7]([O:8]Cc2ccccc2)[cH:9][cH:10][c:11]1[N+:12](=O)[O-]>>[CH3:1][c:2]1[cH:3][c:4]2[c:5]([F:6])[c:7]([OH:8])[cH:9][cH:10][c:11]2[nH:12]1
CC(=O)Cc1c([N+](=O)[O-])ccc(OCc2ccccc2)c1F
Cc1cc2c(F)c(O)ccc2[nH]1
null
[Pd]
C(C)(=O)O.C(C)O
Functional Group Interconversion
OtherReaction
3cfd66aaccb0cd1068889acfd02b7b8ae9adf44c824547ae1bc175897a5df52d
6868311343724373887f566a45c0a5e9970d44496fd22223969e86834cb40b47
c1ccc2[nH]ccc2c1
O=[C;H0;D3;+0:1](-[C;D1;H3:2])-[CH2;D2;+0:3]-[c:4]1:[c:5]:[c:6](-[O;H0;D2;+0:7]-C-c2:c:c:c:c:c:2):[c:8]:[c:9]:[c:10]:1-[N+;H0;D3:11](=O)-[O-]>>[C;D1;H3:2]-[c;H0;D3;+0:1]1:[cH;D2;+0:3]:[c:4]2:[c:5]:[c:6](-[OH;D1;+0:7]):[c:8]:[c:9]:[c:10]:2:[nH;D2;+0:11]:1
null
[]
null
null
2
HOUR
A solution of 3-acetylmethyl-1-benzyloxy-2-fluoro-4-nitrobenzene (300 mg, 0.99 mmol) in ethanol (10 ml) and acetic acid (1 ml) containing 10% palladium on charcoal (30 mg) was hydrogenated at 2 atmospheres pressure for 2 hours. The mixture was filtered and the filtrate was evaporated. The residue was dissolved in ethyl...
10.6084/m9.figshare.5104873.v1
null
Ketone.Ether.Nitro group
Aromatic alcohol
c1ccccc1.c1ccccc1
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1
HO-
[Pd].C(C)(=O)O.C(C)O
null
2
CC(=O)Cc1c([N+](=O)[O-])ccc(OCc2ccccc2)c1F>[Pd].C(C)(=O)O.C(C)O>Cc1cc2c(F)c(O)ccc2[nH]1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-015cb96a7af248c4b21963a09711d662
COC(C)(Cc1c([N+](=O)[O-])ccc(F)c1F)OC.C[O-]>>COc1ccc([N+](=O)[O-])c(CC(C)=O)c1F
C[O-].[Na+].[Na].FC1=C(C(=C(C=C1)[N+](=O)[O-])CC(C)(OC)OC)F>>C(C)(=O)CC=1C(=C(C=CC1[N+](=O)[O-])OC)F
CO[C:12]([CH2:11][c:10]1[c:6]([N+:7](=[O:8])[O-:9])[cH:5][cH:4][c:3](F)[c:15]1[F:16])([CH3:13])[O:14]C.[CH3:1][O-:2]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([N+:7](=[O:8])[O-:9])[c:10]([CH2:11][C:12]([CH3:13])=[O:14])[c:15]1[F:16]
COC(C)(Cc1c([N+](=O)[O-])ccc(F)c1F)OC.C[O-]
COc1ccc([N+](=O)[O-])c(CC(C)=O)c1F
null
null
CO
Acylation
OtherReaction
62ce2b56333bfce32973170f27f1edca736847b0cf82171fd484e2a7bba55be5
5fc8711396a819699ce779336b7bfdeaaaa6fc024e8ddd484dcc51d216e6ca39
c1ccccc1
C-O-[C;H0;D4;+0:1](-[C;D1;H3:2])(-[C:3]-[c:4]:[c:5](-[F;D1;H0:6]):[c;H0;D3;+0:7](-F):[c:8]:[c:9])-[O;H0;D2;+0:10]-C.[C;D1;H3:11]-[O-;H0;D1:12]>>[C;D1;H3:2]-[C;H0;D3;+0:1](=[O;H0;D1;+0:10])-[C:3]-[c:4]:[c:5](-[F;D1;H0:6]):[c;H0;D3;+0:7](-[O;H0;D2;+0:12]-[C;D1;H3:11]):[c:8]:[c:9]
90
[{"value": 90.0, "product": "C(C)(=O)CC=1C(=C(C=CC1[N+](=O)[O-])OC)F", "details": "PERCENTYIELD", "is_desired": false}]
5
CELSIUS
3
DAY
A solution of sodium methoxide (freshly prepared from sodium (1.71 g) and methanol (35 ml)) was added to a solution of 1,2-difluoro-3-(2,2-dimethoxypropyl)-4-nitrobenzene (16.2 g, 62 mmol), (prepared as described above), in methanol (200 ml) cooled at 5° C. The mixture was left to warm to ambient temperature and was st...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Ether.Ether
Ketone.Ether
c1ccccc1
c1ccccc1
c1ccccc1
HF
CO
5
72
COC(C)(Cc1c([N+](=O)[O-])ccc(F)c1F)OC.C[O-]>CO>COc1ccc([N+](=O)[O-])c(CC(C)=O)c1F
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-f265e1a4fa134689937c53e857f7844e
COc1ccc([N+](=O)[O-])c(CC(C)=O)c1F>>COc1ccc2[nH]c(C)cc2c1F
C(C)(=O)CC=1C(=C(C=CC1[N+](=O)[O-])OC)F.C(C)(=O)[O-].[NH4+]>>FC1=C2C=C(NC2=CC=C1OC)C
O=[N+:7]([O-])[c:6]1[cH:5][cH:4][c:3]([O:2][CH3:1])[c:12]([F:13])[c:11]1[CH2:10][C:8](=O)[CH3:9]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[nH:7][c:8]([CH3:9])[cH:10][c:11]2[c:12]1[F:13]
COc1ccc([N+](=O)[O-])c(CC(C)=O)c1F
COc1ccc2[nH]c(C)cc2c1F
null
[Cl-].[Cl-].[Cl-].[Ti+3]
CC(=O)C
Aromatic Heterocycle Formation
OtherReaction
e65c65f0f810d0b59dc9184c320c42fa591a551e8b78a8aea60d36d065df7abe
1c2c81cd7b083137f7463d418ef3bc406dca4f6a8b870047ce0adc41849da5d0
c1ccc2[nH]ccc2c1
O=[C;H0;D3;+0:1](-[C;D1;H3:2])-[CH2;D2;+0:3]-[c:4](:[c:5]):[c:6](-[N+;H0;D3:7](=O)-[O-]):[c:8]>>[C;D1;H3:2]-[c;H0;D3;+0:1]1:[cH;D2;+0:3]:[c:4](:[c:5]):[c:6](:[c:8]):[nH;D2;+0:7]:1
91
[{"value": 90.0, "product": "FC1=C2C=C(NC2=CC=C1OC)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 91.0, "product": "FC1=C2C=C(NC2=CC=C1OC)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
10
MINUTE
To a solution of 3-acetylmethyl-2-fluoro-1-methoxy-4-nitrobenzene (11.36 g, 50 mmol) in acetone (200 ml) was added 4M aqueous ammonium acetate (700 ml) followed by a solution of titanium trichloride (15% in water, 340 ml) dropwise. The mixture was stirred for 10 minutes at ambient temperature and the mixture was extrac...
10.6084/m9.figshare.5104873.v1
null
Ketone.Nitro group
null
c1ccccc1
c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1
Other
[Cl-].[Cl-].[Cl-].[Ti+3].CC(=O)C
null
0.166667
COc1ccc([N+](=O)[O-])c(CC(C)=O)c1F>[Cl-].[Cl-].[Cl-].[Ti+3].CC(=O)C>COc1ccc2[nH]c(C)cc2c1F
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-21f746e8a64044cf85d466f803ad72f9
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Cc1cc2c(F)c(O)ccc2[nH]1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OCCCN1CCCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1.FC1=C2C=C(NC2=CC=C1O)C>>FC1=C2C=C(NC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1)C
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:24]([O:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:30][CH2:31][CH2:32][CH2:33][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][c...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Cc1cc2c(F)c(O)ccc2[nH]1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OCCCN1CCCCC1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCCCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
83.6
[{"value": 83.0, "product": "FC1=C2C=C(NC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 83.6, "product": "FC1=C2C=C(NC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 237, 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (1.65 g, 4.89 mmol), (prepared as described for the starting material in Example 67), was reacted with 4-fluoro-5-hydroxy-2-methylindole (970 mg, 5.88 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]CC1
HCl
null
null
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Cc1cc2c(F)c(O)ccc2[nH]1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OCCCN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a990c8a7c1a3441894bfa8a646697edd
COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1.Cc1cc2c(F)c(O)ccc2[nH]1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OCCCN1CCN(C)CC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C.FC1=C2C=C(NC2=CC=C1O)C>>FC1=C2C=C(NC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(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][CH2:28][N:29]3[CH2:30][CH2:31][N:32]([CH3:33])[CH2:34][CH2:35]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[...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1.Cc1cc2c(F)c(O)ccc2[nH]1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OCCCN1CCN(C)CC1
null
null
null
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]
70
[{"value": 70.0, "product": "FC1=C2C=C(NC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 69.5, "product": "FC1=C2C=C(NC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 237, 4-chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline (106 mg, 0.30 mmol), (prepared as described for the starting material in Example 176), was reacted with 4-fluoro-5-hydroxy-2methylindole (60 mg, 0.36 mmol), (prepared as described for the s...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1C[NH]CC[NH]1
HCl
null
null
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1.Cc1cc2c(F)c(O)ccc2[nH]1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OCCCN1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-8172a8567c7c4f47b569dad2c8d59417
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1cc2c(F)c(O)ccc2[nH]1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OCCCN1CCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1.FC1=C2C=C(NC2=CC=C1O)C>>FC1=C2C=C(NC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1)C
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:24]([O:25][CH2:26][CH2:27][CH2:28][N:29]3[CH2:30][CH2:31][CH2:32][CH2:33]3)[cH:23][c:22]2[n:21][cH:20][n:19]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[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][c:13]([CH...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1cc2c(F)c(O)ccc2[nH]1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OCCCN1CCCC1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
50.3
[{"value": 50.0, "product": "FC1=C2C=C(NC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 50.3, "product": "FC1=C2C=C(NC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using a procedure identical to that described in Example 237, 4-chloro-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline (2 g, 6.22 mmol), (prepared as described for the starting material in Example 9), was reacted with 4-fluoro-5-hydroxy-2-methylindole (1.23 g, 7.46 mmol), (prepared as described for the starting mat...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]C1
HCl
null
null
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1cc2c(F)c(O)ccc2[nH]1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3F)ncnc2cc1OCCCN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-09b16722bd8d42038922d9843d4354a8
COc1cc2c(Cl)ncnc2cc1OCCC1CCN(C)CC1.Oc1ccc2[nH]ccc2c1F>>COc1cc2c(Oc3ccc4[nH]ccc4c3F)ncnc2cc1OCCC1CCN(C)CC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCC1CCN(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)OCCC1CCN(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][CH:27]3[CH2:28][CH2:29][N:30]([CH3:31])[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[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:13][cH...
COc1cc2c(Cl)ncnc2cc1OCCC1CCN(C)CC1.Oc1ccc2[nH]ccc2c1F
COc1cc2c(Oc3ccc4[nH]ccc4c3F)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]
69.6
[{"value": 69.0, "product": "FC1=C2C=CNC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCC1CCN(CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 69.6, "product": "FC1=C2C=CNC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCC1CCN(CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
90
CELSIUS
1
HOUR
A solution of 4-chloro-6-methoxy-7-(2-(1-methylpiperidin-4-yl)ethoxy)quinazoline (300 mg, 0.9 mmol) and 4-fluoro-5-hydroxyindole (162 mg, 1 mmol), (prepared as described for the starting material in Example 242), in DMF (4.5 ml) containing potassium carbonate (185 mg, 1.3 mmol) was stirred at 90° C. for 1 hour. After c...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
CN(C)C=O
90
1
COc1cc2c(Cl)ncnc2cc1OCCC1CCN(C)CC1.Oc1ccc2[nH]ccc2c1F>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]ccc4c3F)ncnc2cc1OCCC1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-12857671bd7645b1b73a6f9d93710026
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O.Cc1ccc(S(=O)(=O)OCCC2CCN(C(=O)OC(C)(C)C)CC2)cc1>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCC1CCN(C(=O)OC(C)(C)C)CC1
OC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC.CC1=CC=C(C=C1)S(=O)(=O)OCCC1CCN(CC1)C(=O)OC(C)(C)C.C([O-])([O-])=O.[K+].[K+]>>C(C)(C)(C)OC(=O)N1CCC(CC1)CCOC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6](=[O:7])[n:8]([CH2:9][O:10][C:11](=[O:12])[C:13]([CH3:14])([CH3:15])[CH3:16])[cH:17][n:18][c:19]2[cH:20][c:21]1[OH:22].Cc1ccc(S(=O)(=O)O[CH2:23][CH2:24][CH:25]2[CH2:26][CH2:27][N:28]([C:29](=[O:30])[O:31][C:32]([CH3:33])([CH3:34])[CH3:35])[CH2:36][CH2:37]2)cc1>>[CH3:1][O:2][c:3]1[cH:4...
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O.Cc1ccc(S(=O)(=O)OCCC2CCN(C(=O)OC(C)(C)C)CC2)cc1
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCC1CCN(C(=O)OC(C)(C)C)CC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
OtherReaction
b5213736859cf91483a02f350869986d9b7674724716adef8a5d7a4bbdb79574
3d107e624e135e10014c7bf413dd0be27e1e4488f039e545b94cb1680b764158
O=c1[nH]cnc2cc(OCCC3CCNCC3)ccc12
C-c1:c:c:c(-S(=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]
88.2
[{"value": 88.0, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)CCOC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 88.2, "product": "C(C)(C)(C)OC(=O)N1CCC(CC1)CCOC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
3
HOUR
A suspension of 7-hydroxy-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (7 g, 23 mmol), (prepared as described for the starting material in Example 12), 4-(2-(4-methylphenylsulphonyloxy)ethyl)-1-tert-butoxycarbonylpiperidine (11.4 g, 30 mmol) in DMF (70 ml) containing potassium carbonate (6.32 g, 46 mmo...
10.6084/m9.figshare.5104873.v1
null
Tosylate.Aromatic alcohol
Ether
c1ccccc1
null
c1ccc2ncncc2c1.C1CC[NH]CC1
TsOH.HO-
CN(C)C=O
100
3
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O.Cc1ccc(S(=O)(=O)OCCC2CCN(C(=O)OC(C)(C)C)CC2)cc1>CN(C)C=O>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCC1CCN(C(=O)OC(C)(C)C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b62228dabf2c4e3f8837fd4882fb76a8
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCC1CCN(C(=O)OC(C)(C)C)CC1>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCC1CCNCC1
C(O)([O-])=O.[Na+].O.C(C)(C)(C)OC(=O)N1CCC(CC1)CCOC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC.C(=O)(C(F)(F)F)O>>N1CCC(CC1)CCOC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC
CC(C)(C)OC(=O)[N:28]1[CH2:27][CH2:26][CH:25]([CH2:24][CH2:23][O:22][c:21]2[c:3]([O:2][CH3:1])[cH:4][c:5]3[c:6](=[O:7])[n:8]([CH2:9][O:10][C:11](=[O:12])[C:13]([CH3:14])([CH3:15])[CH3:16])[cH:17][n:18][c:19]3[cH:20]2)[CH2:30][CH2:29]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6](=[O:7])[n:8]([CH2:9][O:10][C:11](=[O:12])[C:13]([...
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCC1CCN(C(=O)OC(C)(C)C)CC1
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCC1CCNCC1
null
null
C(Cl)Cl
Reduction
Boc amine deprotection
bf3cd5dc3e17e694d8665c89f5d7e08e8763b18436a633eb66e9bf530b8b0316
a94b29c7264c852156fc1cdd4a0951a4fc26c06d0edc9e50c743825dbf79e3fd
O=c1[nH]cnc2cc(OCCC3CCNCC3)ccc12
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]
100
[{"value": 100.0, "product": "N1CCC(CC1)CCOC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 99.4, "product": "N1CCC(CC1)CCOC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
A solution of 7-(2-(1-tert-butoxycarbonylpiperidin-4-yl)ethoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (10.5 g, 20 mmol) in methylene chloride (100 ml) containing TFA (25 ml) was stirred for 1 hour at ambient temperature. Water (50 ml) and methylene chloride (100 ml) were added and the pH of the ...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
C1CC[NH]CC1
C1CCNCC1
c1ccc2ncncc2c1.C1CCNCC1
HO-
C(Cl)Cl
null
1
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCC1CCN(C(=O)OC(C)(C)C)CC1>C(Cl)Cl>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCC1CCNCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-53b23347ca994bbbb2fb431adf14d47d
C=O.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCC1CCNCC1>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCC1CCN(C)CC1
C(C)(=O)O.C(C)(=O)O.C(C)(=O)O.[BH4-].[Na+].C(C)(=O)O.N1CCC(CC1)CCOC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC.C=O>>CN1CCC(CC1)CCOC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC
O=[CH2:29].[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6](=[O:7])[n:8]([CH2:9][O:10][C:11](=[O:12])[C:13]([CH3:14])([CH3:15])[CH3:16])[cH:17][n:18][c:19]2[cH:20][c:21]1[O:22][CH2:23][CH2:24][CH:25]1[CH2:26][CH2:27][NH:28][CH2:30][CH2:31]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6](=[O:7])[n:8]([CH2:9][O:10][C:11](=[O:12])[C:13]([CH3:14...
C=O.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCC1CCNCC1
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCC1CCN(C)CC1
null
null
C(Cl)Cl.CO
Heteroatom Alkylation and Arylation
Eschweiler-Clarke Secondary Amine Methylation
e23db47f33553519e7237e30c3b19a21fcbb90bde44fbb5566021920bc9b7164
e1fdef8fde1c506d7c9deb8fd5e6f322eceea2abce3167abcf412a1fa4fd5443
O=c1[nH]cnc2cc(OCCC3CCNCC3)ccc12
O=[CH2;D1;+0:1].[C:2]-[C:3]-[NH;D2;+0:4]-[C:5]-[C:6]>>[C:2]-[C:3]-[N;H0;D3;+0:4](-[CH3;D1;+0:1])-[C:5]-[C:6]
68
[{"value": 68.0, "product": "CN1CCC(CC1)CCOC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 67.6, "product": "CN1CCC(CC1)CCOC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
To a solution of 7-(2-(piperidin-4-yl)ethoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (6 g, 14.4 mmol) in methanol (30 ml) and methylene chloride (60 ml) was added 37% aqueous formaldehyde (2.2 ml; 28.9 mmol) followed by acetic acid (990 μl; 17.3 mmol). Sodium borohydride triacetate (4.6 g, 21.6 m...
10.6084/m9.figshare.5104873.v1
null
Formaldehyde.Secondary amine
Tertiary amine
C1CCNCC1
C1CC[NH]CC1
c1ccc2ncncc2c1.C1CC[NH]CC1
Other
C(Cl)Cl.CO
null
1
C=O.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCC1CCNCC1>C(Cl)Cl.CO>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCC1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-fdf85d2b5d344a6ab7a1ac655e9bb8a1
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCC1CCN(C)CC1>>COc1cc2c(=O)[nH]cnc2cc1OCCC1CCN(C)CC1
CN1CCC(CC1)CCOC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC.N>>CN1CCC(CC1)CCOC1=C(C=C2C(NC=NC2=C1)=O)OC
CC(C)(C)C(=O)OC[n:8]1[c:6](=[O:7])[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:13]([O:14][CH2:15][CH2:16][CH:17]3[CH2:18][CH2:19][N:20]([CH3:21])[CH2:22][CH2:23]3)[cH:12][c:11]2[n:10][cH:9]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6](=[O:7])[nH:8][cH:9][n:10][c:11]2[cH:12][c:13]1[O:14][CH2:15][CH2:16][CH:17]1[CH2:18][CH2:19][N:20]([CH3...
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCC1CCN(C)CC1
COc1cc2c(=O)[nH]cnc2cc1OCCC1CCN(C)CC1
null
null
CO
Reduction
OtherReaction
9f6991089c15fc054898797f1d3a42b158e517f125611bc103acfc00878b3b20
b8e5da8ea19c403a2e974791a9cf591400749acb6b71151717aaece4f3b22bef
O=c1[nH]cnc2cc(OCCC3CCNCC3)ccc12
C-C(-C)(-C)-C(=O)-O-C-[n;H0;D3;+0:1]1:[c:2]:[#7;a:3]:[c:4]:[c:5]:[c:6]:1=[O;D1;H0:7]>>[O;D1;H0:7]=[c:6]1:[c:5]:[c:4]:[#7;a:3]:[c:2]:[nH;D2;+0:1]:1
101.3
[{"value": 100.0, "product": "CN1CCC(CC1)CCOC1=C(C=C2C(NC=NC2=C1)=O)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 101.3, "product": "CN1CCC(CC1)CCOC1=C(C=C2C(NC=NC2=C1)=O)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 7-(2-(1-methylpiperidin-4-yl)ethoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (4.2 g, 9.7 mmol) in methanol saturated with ammonia (150 ml) was stirred overnight at ambient temperature. The volatiles were removed under vacuum and the residue was triturated with ether. The solid was fi...
10.6084/m9.figshare.5104873.v1
null
Ester
null
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1CC[NH]CC1
HO-
CO
null
null
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCC1CCN(C)CC1>CO>COc1cc2c(=O)[nH]cnc2cc1OCCC1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-1821216e182c4f2085528200cb39298b
COc1cc2c(=O)[nH]cnc2cc1OCCC1CCN(C)CC1.O=S(Cl)Cl>>COc1cc2c(Cl)ncnc2cc1OCCC1CCN(C)CC1
CN1CCC(CC1)CCOC1=C(C=C2C(NC=NC2=C1)=O)OC.CN(C)C=O.S(=O)(Cl)Cl>>ClC1=NC=NC2=CC(=C(C=C12)OC)OCCC1CCN(CC1)C
O=[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:13]([O:14][CH2:15][CH2:16][CH:17]3[CH2:18][CH2:19][N:20]([CH3:21])[CH2:22][CH2:23]3)[cH:12][c:11]2[n:10][cH:9][nH:8]1.O=S(Cl)[Cl:7]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([Cl:7])[n:8][cH:9][n:10][c:11]2[cH:12][c:13]1[O:14][CH2:15][CH2:16][CH:17]1[CH2:18][CH2:19][N:20]([CH3:21])[C...
COc1cc2c(=O)[nH]cnc2cc1OCCC1CCN(C)CC1.O=S(Cl)Cl
COc1cc2c(Cl)ncnc2cc1OCCC1CCN(C)CC1
null
null
null
Functional Group Interconversion
OtherReaction
3788560e87eee8765e749543914a91a512631307b97fad163ebef894d2a0ea68
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ncc2ccc(OCCC3CCNCC3)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]
54
[{"value": 54.0, "product": "ClC1=NC=NC2=CC(=C(C=C12)OC)OCCC1CCN(CC1)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 7-(2-(1-methylpiperidin-4-yl)ethoxy)-6-methoxy-3,4-dihydroquinazolin-4-one (3.1 g, 9.8 mmol) in thionyl chloride (40 ml) containing DMF (400 μl) was refluxed for 4 hours. After cooling, the volatiles were removed under vacuum. The residue was partitioned between methylene chloride and water and the pH of ...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
null
null
null
COc1cc2c(=O)[nH]cnc2cc1OCCC1CCN(C)CC1.O=S(Cl)Cl>>COc1cc2c(Cl)ncnc2cc1OCCC1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-eb76b60177fc472895a455c1d233b63a
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Oc1cc2cc[nH]c2cc1F>>COc1cc2c(Oc3cc4cc[nH]c4cc3F)ncnc2cc1OCC1CCN(C)CC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C.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)OCC1CCN(CC1)C
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:23]([O:24][CH2:25][CH:26]3[CH2:27][CH2:28][N:29]([CH3:30])[CH2:31][CH2:32]3)[cH:22][c:21]2[n:20][cH:19][n:18]1.[OH:7][c:8]1[cH:9][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]4[cH:...
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Oc1cc2cc[nH]c2cc1F
COc1cc2c(Oc3cc4cc[nH]c4cc3F)ncnc2cc1OCC1CCN(C)CC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCC3CCNCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
46.7
[{"value": 46.0, "product": "FC1=C(C=C2C=CNC2=C1)OC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 46.7, "product": "FC1=C(C=C2C=CNC2=C1)OC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
95
CELSIUS
3.5
HOUR
A solution of 4-chloro-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazoline (213 mg, 0.662 mmol), (prepared as described for the starting material in Example 10), and 6-fluoro-5-hydroxyindole (120 mg, 0.794 mmol) in DMF (3 ml) containing potassium carbonate (137 mg, 0.994 mmol) was stirred at 95° C. for 3.5 hours. ...
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
3.5
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Oc1cc2cc[nH]c2cc1F>CN(C)C=O>COc1cc2c(Oc3cc4cc[nH]c4cc3F)ncnc2cc1OCC1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-564d401599b3426780f7b4dd1bfcdf47
BrCc1ccccc1.O=[N+]([O-])c1ccc(O)c(F)c1>>O=[N+]([O-])c1ccc(OCc2ccccc2)c(F)c1
FC1=C(C=CC(=C1)[N+](=O)[O-])O.C(C1=CC=CC=C1)Br.C([O-])([O-])=O.[K+].[K+]>>FC1=C(C=CC(=C1)[N+](=O)[O-])OCC1=CC=CC=C1
Br[CH2:9][c:10]1[cH:11][cH:12][cH:13][cH:14][cH:15]1.[O:1]=[N+:2]([O-:3])[c:4]1[cH:5][cH:6][c:7]([OH:8])[c:16]([F:17])[cH:18]1>>[O:1]=[N+:2]([O-:3])[c:4]1[cH:5][cH:6][c:7]([O:8][CH2:9][c:10]2[cH:11][cH:12][cH:13][cH:14][cH:15]2)[c:16]([F:17])[cH:18]1
BrCc1ccccc1.O=[N+]([O-])c1ccc(O)c(F)c1
O=[N+]([O-])c1ccc(OCc2ccccc2)c(F)c1
null
null
CC(=O)C
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
7e1040116e3a4cf0e8ec5cc7865388d9cd0efabce6d320a1c25a36e411018d8b
d5f4610d46ccc0478471c5bc0fb862644eaf764bbc5d93badb39d54f6ec8e0a5
c1ccc(COc2ccccc2)cc1
Br-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[OH;D1;+0:5]-[c:6](:[c:7]):[c:8]>>[c:3]:[c:2](-[CH2;D2;+0:1]-[O;H0;D2;+0:5]-[c:6](:[c:7]):[c:8]):[c:4]
97.4
[{"value": 97.0, "product": "FC1=C(C=CC(=C1)[N+](=O)[O-])OCC1=CC=CC=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 97.4, "product": "FC1=C(C=CC(=C1)[N+](=O)[O-])OCC1=CC=CC=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A mixture of 2-fluoro-4-nitrophenol (15 gr, 95.5 mmol) and benzyl bromide (18 g, 105 mmol) in acetone (125 ml) containing potassium carbonate (26.5 gr, 190 mmol) was refluxed for 2 hours. The volatiles were removed and the residue was partitioned between 2N hydrochloric acid and ethyl acetate. The organic layer was sep...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Aromatic alcohol
Ether
null
null
c1ccccc1.c1ccccc1
HBr
CC(=O)C
null
null
BrCc1ccccc1.O=[N+]([O-])c1ccc(O)c(F)c1>CC(=O)C>O=[N+]([O-])c1ccc(OCc2ccccc2)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-9ba4c4b48e2c4954a923bfc60600b34d
N#CCc1c([N+](=O)[O-])ccc(OCc2ccccc2)c1F.N#CCc1cc(OCc2ccccc2)c(F)cc1[N+](=O)[O-]>>Oc1cc2cc[nH]c2cc1F.Oc1ccc2[nH]ccc2c1F
[H][H].C(#N)CC=1C(=C(C=CC1[N+](=O)[O-])OCC1=CC=CC=C1)F.C(#N)CC=1C(=CC(=C(C1)OCC1=CC=CC=C1)F)[N+](=O)[O-]>>FC1=C2C=CNC2=CC=C1O.FC1=C(C=C2C=CNC2=C1)O
N#[C:18][CH2:19][c:20]1[c:16]([N+:17](=O)[O-])[cH:15][cH:14][c:13]([O:12]Cc2ccccc2)[c:21]1[F:22].N#[C:6][CH2:5][c:4]1[cH:3][c:2]([O:1]Cc2ccccc2)[c:10]([F:11])[cH:9][c:8]1[N+:7](=O)[O-]>>[OH:1][c:2]1[cH:3][c:4]2[cH:5][cH:6][nH:7][c:8]2[cH:9][c:10]1[F:11].[OH:12][c:13]1[cH:14][cH:15][c:16]2[nH:17][cH:18][cH:19][c:20]2[c:...
N#CCc1c([N+](=O)[O-])ccc(OCc2ccccc2)c1F.N#CCc1cc(OCc2ccccc2)c(F)cc1[N+](=O)[O-]
Oc1cc2cc[nH]c2cc1F.Oc1ccc2[nH]ccc2c1F
null
[Pd]
C(C)(=O)O.C(C)O
Functional Group Interconversion
OtherReaction
05691dbe7c2ab021a56e9125081203d6f1c1149136906e9fc07f5042afff0423
4410a65284fe09beb1aa79170ec5752790a66b9caf187a4e992073c911378273
c1ccc2[nH]ccc2c1.c1ccc2[nH]ccc2c1
N#[C;H0;D2;+0:1]-[CH2;D2;+0:2]-[c:3]1:[c:4]:[c:5](-[O;H0;D2;+0:6]-C-c2:c:c:c:c:c:2):[c:7]:[c:8]:[c:9]:1-[N+;H0;D3:10](=O)-[O-].N#[C;H0;D2;+0:11]-[CH2;D2;+0:12]-[c:13]1:[c:14]:[c:15](-[O;H0;D2;+0:16]-C-c2:c:c:c:c:c:2):[c:17]:[c:18]:[c:19]:1-[N+;H0;D3:20](=O)-[O-]>>[OH;D1;+0:16]-[c:15]1:[c:17]:[c:18]:[c:19]2:[nH;D2;+0:20...
null
[]
null
null
null
null
A solution of a mixture of 3-cyanomethyl-2-fluoro-4-nitrobenzyloxybenzene and 5-cyanomethyl-2-fluoro-4-nitrobenzyloxybenzene (23 g, 80.4 mmol) in ethanol (220 ml) and acetic acid (30 ml) containing 10% palladium on charcoal (600 mg) was hydrogenated under 3 atmospheres pressure until hydrogen uptake ceased. The mixture...
10.6084/m9.figshare.5104873.v1
null
Ether.Ether.Nitrile.Nitrile.Nitro group.Nitro group
Aromatic alcohol.Aromatic alcohol
c1ccccc1.c1ccccc1.c1ccccc1.c1ccccc1
c1ccc2[nH]ccc2c1.c1ccc2[nH]ccc2c1
c1ccc2[nH]ccc2c1.c1ccc2[nH]ccc2c1
HO-
[Pd].C(C)(=O)O.C(C)O
null
null
N#CCc1c([N+](=O)[O-])ccc(OCc2ccccc2)c1F.N#CCc1cc(OCc2ccccc2)c(F)cc1[N+](=O)[O-]>[Pd].C(C)(=O)O.C(C)O>Oc1cc2cc[nH]c2cc1F.Oc1ccc2[nH]ccc2c1F
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-07a0940d50ee47c797df5fb99135b619
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Oc1ccc2[nH]ccc2c1F>>COc1cc2c(Oc3ccc4[nH]ccc4c3F)ncnc2cc1OCC1CCN(C)CC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(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)OCC1CCN(CC1)C
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:23]([O:24][CH2:25][CH:26]3[CH2:27][CH2:28][N:29]([CH3:30])[CH2:31][CH2:32]3)[cH:22][c:21]2[n:20][cH:19][n:18]1.[OH:7][c:8]1[cH:9][cH:10][c:11]2[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:13][cH:14][c:1...
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Oc1ccc2[nH]ccc2c1F
COc1cc2c(Oc3ccc4[nH]ccc4c3F)ncnc2cc1OCC1CCN(C)CC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCC3CCNCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
26.6
[{"value": 26.0, "product": "FC1=C2C=CNC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 26.6, "product": "FC1=C2C=CNC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCC1CCN(CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
95
CELSIUS
3
HOUR
A solution of 4-chloro-6-methoxy-7-((1-methylpiperidin-4-yl)methoxy)quinazoline (213 mg, 0.662 mmol), (prepared as described for the starting material in Example 10), 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 potassium c...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1
HCl
CN(C)C=O
95
3
COc1cc2c(Cl)ncnc2cc1OCC1CCN(C)CC1.Oc1ccc2[nH]ccc2c1F>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]ccc4c3F)ncnc2cc1OCC1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e608bf7365d449748c1e5ee65ea4dba7
COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1.Oc1cc2cc[nH]c2cc1F>>COc1cc2c(Oc3cc4cc[nH]c4cc3F)ncnc2cc1OCCCN1CCN(C)CC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C.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)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][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...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1.Oc1cc2cc[nH]c2cc1F
COc1cc2c(Oc3cc4cc[nH]c4cc3F)ncnc2cc1OCCCN1CCN(C)CC1
null
null
O.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]
48
[{"value": 48.0, "product": "FC1=C(C=C2C=CNC2=C1)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 47.7, "product": "FC1=C(C=C2C=CNC2=C1)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
95
CELSIUS
null
null
A mixture of 4-chloro-6-methoxy-7-(3-(4-methylpiperazin-1-yl)propoxy)quinazoline (282 mg, 0.662 mmol), 6-fluoro-5-hydroxyindole (120 mg, 0.794 mmol), (prepared as described for the starting material in Example 242), in DMF (3 ml) containing potassium carbonate (137 mg, 0.994 mmol) was heated at 95° C. for 3 hours. Afte...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1C[NH]CC[NH]1
HCl
O.CN(C)C=O
95
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1.Oc1cc2cc[nH]c2cc1F>O.CN(C)C=O>COc1cc2c(Oc3cc4cc[nH]c4cc3F)ncnc2cc1OCCCN1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b36d13133fb74c5992bcae9767b50b0e
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O.OCCCBr>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr
N(=NC(=O)OCC)C(=O)OCC.OC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.BrCCCO>>BrCCCOC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6](=[O:7])[n:8]([CH2:9][O:10][C:11](=[O:12])[C:13]([CH3:14])([CH3:15])[CH3:16])[cH:17][n:18][c:19]2[cH:20][c:21]1[OH:22].O[CH2:23][CH2:24][CH2:25][Br:26]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6](=[O:7])[n:8]([CH2:9][O:10][C:11](=[O:12])[C:13]([CH3:14])([CH3:15])[CH3:16])[cH:17][n:18][c:19]2...
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O.OCCCBr
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr
null
null
C(Cl)Cl
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
O=c1[nH]cnc2ccccc12
O-[CH2;D2;+0:1]-[C:2]-[C:3].[#7;a:4]:[c:5]:[c:6]:[c:7](-[OH;D1;+0:8]):[c:9]>>[#7;a:4]:[c:5]:[c:6]:[c:7](-[O;H0;D2;+0:8]-[CH2;D2;+0:1]-[C:2]-[C:3]):[c:9]
92
[{"value": 92.0, "product": "BrCCCOC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 92.0, "product": "BrCCCOC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
To a suspension of 7-hydroxy-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (29 g, 94.7 mmol), (prepared as described for the starting material in Example 12), in methylene chloride (280 ml) colled at 5° C. was added triphenylphosphine (37.1 g, 141.6 mmol) followed by 3-bromo-1-propanol (12.8 ml, 141.6 m...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccc2ncncc2c1
HO-
C(Cl)Cl
null
2
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1O.OCCCBr>C(Cl)Cl>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-39acf0447c3f4b10847017e43e410dc4
CN1CCNCC1.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCN(C)CC1
BrCCCOC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC.CN1CCNCC1>>CN1CCN(CC1)CCCOC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC
[NH:26]1[CH2:27][CH2:28][N:29]([CH3:30])[CH2:31][CH2:32]1.Br[CH2:25][CH2:24][CH2:23][O:22][c:21]1[c:3]([O:2][CH3:1])[cH:4][c:5]2[c:6](=[O:7])[n:8]([CH2:9][O:10][C:11](=[O:12])[C:13]([CH3:14])([CH3:15])[CH3:16])[cH:17][n:18][c:19]2[cH:20]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6](=[O:7])[n:8]([CH2:9][O:10][C:11](=[O:12])[C:...
CN1CCNCC1.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCN(C)CC1
null
null
null
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
bad6b7d8e43c3debef0c262d60564e43415b41bcee72e526419c8c16be18fec1
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
O=c1[nH]cnc2cc(OCCCN3CCNCC3)ccc12
Br-[CH2;D2;+0:1]-[C:2]-[C:3].[#7:4]1-[C:5]-[C:6]-[NH;D2;+0:7]-[C:8]-[C:9]-1>>[C:3]-[C:2]-[CH2;D2;+0:1]-[N;H0;D3;+0:7]1-[C:6]-[C:5]-[#7:4]-[C:9]-[C:8]-1
83
[{"value": 83.0, "product": "CN1CCN(CC1)CCCOC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC", "details": "PERCENTYIELD", "is_desired": false}]
100
CELSIUS
90
MINUTE
A suspension of 7-(3-bromopropoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (36.7 g, 86 mmol) in 1-methylpiperazine (370 ml) was stirred at 100° C. for 90 minutes. After removal of the volatiles under vacuum, the residue was partitioned between methylene chloride and aqueous ammonium chloride. The ...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1CNCC[NH]1
C1C[NH]CC[NH]1
c1ccc2ncncc2c1.C1C[NH]CC[NH]1
HBr
null
100
1.5
CN1CCNCC1.COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCBr>>COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-93c9f371cee641829e25238921c4f162
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCN(C)CC1>>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCN(C)CC1
CN1CCN(CC1)CCCOC1=C(C=C2C(N(C=NC2=C1)COC(C(C)(C)C)=O)=O)OC.N>>CN1CCN(CC1)CCCOC1=C(C=C2C(NC=NC2=C1)=O)OC
CC(C)(C)C(=O)OC[n:8]1[c:6](=[O:7])[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:13]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:19][CH2:20][N:21]([CH3:22])[CH2:23][CH2:24]3)[cH:12][c:11]2[n:10][cH:9]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6](=[O:7])[nH:8][cH:9][n:10][c:11]2[cH:12][c:13]1[O:14][CH2:15][CH2:16][CH2:17][N:18]1[CH2:19][CH2:...
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCN(C)CC1
COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCN(C)CC1
null
null
CO
Reduction
OtherReaction
9f6991089c15fc054898797f1d3a42b158e517f125611bc103acfc00878b3b20
b8e5da8ea19c403a2e974791a9cf591400749acb6b71151717aaece4f3b22bef
O=c1[nH]cnc2cc(OCCCN3CCNCC3)ccc12
C-C(-C)(-C)-C(=O)-O-C-[n;H0;D3;+0:1]1:[c:2]:[#7;a:3]:[c:4]:[c:5]:[c:6]:1=[O;D1;H0:7]>>[O;D1;H0:7]=[c:6]1:[c:5]:[c:4]:[#7;a:3]:[c:2]:[nH;D2;+0:1]:1
95.5
[{"value": 95.0, "product": "CN1CCN(CC1)CCCOC1=C(C=C2C(NC=NC2=C1)=O)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 95.5, "product": "CN1CCN(CC1)CCCOC1=C(C=C2C(NC=NC2=C1)=O)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
A suspension of 7-(3-(4-methylpiperazin-1-yl)propoxy)-6-methoxy-3-((pivaloyloxy)methyl)-3,4-dihydroquinazolin-4-one (31.8 g, 71.3 mmol) in methanol saturated with ammonia was stirred at ambient temperature overnight. The volatiles were removed under vacuum. The solid was triturated with ether containing about 10% of me...
10.6084/m9.figshare.5104873.v1
null
Ester
null
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1C[NH]CC[NH]1
HO-
CO
null
8
COc1cc2c(=O)n(COC(=O)C(C)(C)C)cnc2cc1OCCCN1CCN(C)CC1>CO>COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-dab3f9c43bc744b18a88b00b23977c4f
COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCN(C)CC1.O=S(Cl)Cl>>COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1
CN1CCN(CC1)CCCOC1=C(C=C2C(NC=NC2=C1)=O)OC.CN(C)C=O.S(=O)(Cl)Cl>>ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C
O=[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:13]([O:14][CH2:15][CH2:16][CH2:17][N:18]3[CH2:19][CH2:20][N:21]([CH3:22])[CH2:23][CH2:24]3)[cH:12][c:11]2[n:10][cH:9][nH:8]1.O=S(Cl)[Cl:7]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([Cl:7])[n:8][cH:9][n:10][c:11]2[cH:12][c:13]1[O:14][CH2:15][CH2:16][CH2:17][N:18]1[CH2:19][CH2:20][N:2...
COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCN(C)CC1.O=S(Cl)Cl
COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1
null
null
null
Functional Group Interconversion
OtherReaction
3788560e87eee8765e749543914a91a512631307b97fad163ebef894d2a0ea68
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ncc2ccc(OCCCN3CCNCC3)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]
68
[{"value": 68.0, "product": "ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C", "details": "PERCENTYIELD", "is_desired": false}]
0
CELSIUS
null
null
A solution of 7-(3-(4-methylpiperazin-1-yl)propoxy)-6-methoxy-3,4-dihydroquinazolin-4-one (22.6 g, 68 mmol) in thionyl chloride (300 ml) cotaining DMF (5 ml) was refluxed for 2 hours. After cooling, the volatiles were removed under vacuum and the residue was azeotroped with toluene twice. The solid was dissolved in met...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccc2ncncc2c1
c1ccc2ncncc2c1
c1ccc2ncncc2c1.C1C[NH]CC[NH]1
HCl
null
0
null
COc1cc2c(=O)[nH]cnc2cc1OCCCN1CCN(C)CC1.O=S(Cl)Cl>>COc1cc2c(Cl)ncnc2cc1OCCCN1CCN(C)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-699d2ab9eff9457f9c94274b630c1632
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1cc2cc[nH]c2cc1F>>COc1cc2c(Oc3cc4cc[nH]c4cc3F)ncnc2cc1OCCCN1CCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1.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)OCCCN1CCCC1
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][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]4[cH:1...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1cc2cc[nH]c2cc1F
COc1cc2c(Oc3cc4cc[nH]c4cc3F)ncnc2cc1OCCCN1CCCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
53.3
[{"value": 53.0, "product": "FC1=C(C=C2C=CNC2=C1)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 53.3, "product": "FC1=C(C=C2C=CNC2=C1)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 243, 4-chloro-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline (213 mg, 0.662 mmol), (prepared as described for the starting material in Example 9), was reacted with 6-fluoro-5-hydroxyindole (120 mg, 0.794 mmol), (prepared as described for the starting materi...
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
null
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1cc2cc[nH]c2cc1F>CN(C)C=O>COc1cc2c(Oc3cc4cc[nH]c4cc3F)ncnc2cc1OCCCN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-76a63d54b92942e7afe44c57073be5fc
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCNCC1.ClCCN1CCOCC1>>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCN(CCN2CCOCC2)CC1
C(O)([O-])=O.[Na+].Cl.ClCCN1CCOCC1.C(O)([O-])=O.[Na+].COC=1C=C2C(=NC=NC2=CC1OCC1CCNCC1)OC=1C=C2C=C(NC2=CC1)C.[I-].[K+].Cl.ClCCN1CCOCC1>>COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)CCN1CCOCC1)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][CH2:38][CH2:39]1.Cl[CH2:30][CH2:31][N:32]1[CH2:33][CH2:34][O:35][CH2:36][CH2:37]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O...
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCNCC1.ClCCN1CCOCC1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCN(CCN2CCOCC2)CC1
null
null
CO
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
0240b8450ff2c489d02f5f0d90bc953079d7a3ab239d35a03f26392fc248b4ef
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCC3CCN(CCN4CCOCC4)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]
122.8
[{"value": 73.0, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)CCN1CCOCC1)OC=1C=C2C=C(NC2=CC1)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 122.8, "product": "COC=1C=C2C(=NC=NC2=CC1OCC1CCN(CC1)CCN1CCOCC1)OC=1C=C2C=C(NC2=CC1)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
To a solution of 6-methoxy-4-(2-methylindol-5-yloxy)-7-(piperidin-4-ylmethoxy)quinazoline (500 mg, 1.2 mmol), (prepared as described in example 70), in methanol (11.5 ml) containing potassium iodide (99 mg, 0.6 mmol) was added 4-(2chloroethyl)morpholine hydrochloride (134 mg, 0.72 mmol) followed by sodium hydrogen carb...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1CCNCC1
C1CC[NH]CC1
c1ccc2[nH]ccc2c1.c1ccc2ncncc2c1.C1CC[NH]CC1.C1COCC[NH]1
HCl
CO
null
1
COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCNCC1.ClCCN1CCOCC1>CO>COc1cc2c(Oc3ccc4[nH]c(C)cc4c3)ncnc2cc1OCC1CCN(CCN2CCOCC2)CC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e31e0ac7b30d415bba4c77699e97c50c
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1ccc2[nH]ccc2c1F>>COc1cc2c(Oc3ccc4[nH]ccc4c3F)ncnc2cc1OCCCN1CCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1.FC1=C2C=CNC2=CC=C1O.C([O-])([O-])=O.[K+].[K+]>>FC1=C2C=CNC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1
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[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:13][cH:14][c:15...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1ccc2[nH]ccc2c1F
COc1cc2c(Oc3ccc4[nH]ccc4c3F)ncnc2cc1OCCCN1CCCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
52
[{"value": 52.0, "product": "FC1=C2C=CNC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 51.9, "product": "FC1=C2C=CNC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
95
CELSIUS
null
null
A solution of 4-chloro-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline (1.76 g, 5.47 mmol), (prepared as described for the starting material in Example 9), 4-fluoro-5-hydroxyindole (0.992 g, 6.57 mmol), (prepared as described for the starting material in Example 242), in DMF (25 ml) containing potassium carbonate (...
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
95
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Oc1ccc2[nH]ccc2c1F>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]ccc4c3F)ncnc2cc1OCCCN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-04597e881e554ce1a6de9893aef3d4a7
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1cc2cc[nH]c2cc1F>>COc1cc2c(Oc3cc4cc[nH]c4cc3F)ncnc2cc1OCCCN1CCCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1.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)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][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:1...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1cc2cc[nH]c2cc1F
COc1cc2c(Oc3cc4cc[nH]c4cc3F)ncnc2cc1OCCCN1CCCCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCCCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
46.6
[{"value": 46.0, "product": "FC1=C(C=C2C=CNC2=C1)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 46.6, "product": "FC1=C(C=C2C=CNC2=C1)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
95
CELSIUS
null
null
A mixture of 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (222 mg, 0.662 mmol), (prepared as described for the starting material in Example 67), and 6-fluoro-5-hydroxyindole (120 mg, 0.794 mmol), (prepared as described for the starting material in Example 242), in DMF (3 ml) containing potassium carbonate (137...
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
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1cc2cc[nH]c2cc1F>CN(C)C=O>COc1cc2c(Oc3cc4cc[nH]c4cc3F)ncnc2cc1OCCCN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-574866890c9e4bcfb26604f6e4afbdca
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1ccc2[nH]ccc2c1F>>COc1cc2c(Oc3ccc4[nH]ccc4c3F)ncnc2cc1OCCCN1CCCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1.FC1=C2C=CNC2=CC=C1O.C([O-])([O-])=O.[K+].[K+]>>FC1=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[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:13][cH:...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1ccc2[nH]ccc2c1F
COc1cc2c(Oc3ccc4[nH]ccc4c3F)ncnc2cc1OCCCN1CCCCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCCCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
67.3
[{"value": 67.0, "product": "FC1=C2C=CNC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 67.3, "product": "FC1=C2C=CNC2=CC=C1OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
95
CELSIUS
null
null
Using an analogous procedure to that described in Example 244, 4-chloro-6-methoxy-7-(3-piperidinopropoxy)quinazoline (407 mg, 1.21 mmol), (prepared as described for the starting material in Example 67), 4-fluoro-5-hydroxyindole (220 mg, 1.45 mmol) (prepared as described for the starting material in Example 242), and po...
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
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCCC1.Oc1ccc2[nH]ccc2c1F>CN(C)C=O>COc1cc2c(Oc3ccc4[nH]ccc4c3F)ncnc2cc1OCCCN1CCCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-45da1a56bd79459ba378767567fa2054
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1cc2cc(O)c(F)cc2[nH]1>>COc1cc2c(Oc3cc4cc(C)[nH]c4cc3F)ncnc2cc1OCCCN1CCCC1
ClC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1.FC1=C(C=C2C=C(NC2=C1)C)O.C([O-])([O-])=O.[K+].[K+]>>FC1=C(C=C2C=C(NC2=C1)C)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c: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][c:10]2[cH:11][c:12]([CH3:13])[nH:14][c:15]2[cH:16][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][c:10]4[cH:11][c:12]([CH3:13])[...
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1cc2cc(O)c(F)cc2[nH]1
COc1cc2c(Oc3cc4cc(C)[nH]c4cc3F)ncnc2cc1OCCCN1CCCC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2d25b59c80a437134e7830160726da4e12ee4089c37759035843c1cccd8cd262
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1nc(Oc2ccc3[nH]ccc3c2)c2ccc(OCCCN3CCCC3)cc2n1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8].[OH;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[c:11]:[c:10](-[O;H0;D2;+0:9]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](:[c:6]):[c:7]:1:[c:8]):[c:12]
57.3
[{"value": 57.0, "product": "FC1=C(C=C2C=C(NC2=C1)C)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 57.3, "product": "FC1=C(C=C2C=C(NC2=C1)C)OC1=NC=NC2=CC(=C(C=C12)OC)OCCCN1CCCC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 248, 4-chloro-6-methoxy-7-(3-(pyrrolidin-1-yl)propoxy)quinazoline (268 mg, 0.833 mmol), (prepared as described for the starting material in Example 9), was reacted with 6-fluoro-5-hydroxy-2-methylindole (165 mg, 1 mmol) in DMF (3.5 ml) containing potassium carbo...
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
null
null
COc1cc2c(Cl)ncnc2cc1OCCCN1CCCC1.Cc1cc2cc(O)c(F)cc2[nH]1>CN(C)C=O>COc1cc2c(Oc3cc4cc(C)[nH]c4cc3F)ncnc2cc1OCCCN1CCCC1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a44682b619e34067b2df51e2ad64decc
COc1cc2cc(C)[nH]c2cc1F>>Cc1cc2cc(O)c(F)cc2[nH]1
FC1=C(C=C2C=C(NC2=C1)C)OC.B(Br)(Br)Br>>FC1=C(C=C2C=C(NC2=C1)C)O
C[O:7][c:6]1[cH:5][c:4]2[cH:3][c:2]([CH3:1])[nH:12][c:11]2[cH:10][c:8]1[F:9]>>[CH3:1][c:2]1[cH:3][c:4]2[cH:5][c:6]([OH:7])[c:8]([F:9])[cH:10][c:11]2[nH:12]1
COc1cc2cc(C)[nH]c2cc1F
Cc1cc2cc(O)c(F)cc2[nH]1
null
null
C(Cl)Cl
Deprotection
Cleavage of methoxy ethers to alcohols
c5320c7dfa4f544d4900efcae9b3262bf0d5286bcf39c86109232351f35b23d5
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
c1ccc2[nH]ccc2c1
C-[O;H0;D2;+0:1]-[c:2](:[c:3]):[c:4]>>[OH;D1;+0:1]-[c:2](:[c:3]):[c:4]
80
[{"value": 80.0, "product": "FC1=C(C=C2C=C(NC2=C1)C)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 79.9, "product": "FC1=C(C=C2C=C(NC2=C1)C)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
-30
CELSIUS
90
MINUTE
To a solution of 6-fluoro-5-methoxy-2-methylindole (1.23 g, 6.86 mmol), (prepared as described for the starting material in Example 237), in methylene chloride (15 ml) cooled at −30° C. was added a solution of boron tribromide (3.78 g, 15.1 mmol) in methylene chloride (2 ml). After stirring for 90 minutes at ambient te...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
null
null
c1ccc2[nH]ccc2c1
Other
C(Cl)Cl
-30
1.5
COc1cc2cc(C)[nH]c2cc1F>C(Cl)Cl>Cc1cc2cc(O)c(F)cc2[nH]1