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-c31cb9b44c404c10ba3aa533aa079e2b
ord-907218e6526b4b39bc1c602a8542be49
O=C(O)[C@@H](O)[C@H](O)C(=O)O>>O=C([O-])[C@@H](O)[C@H](O)C(=O)[O-]
C([C@@H](O)[C@H](O)C(=O)O)(=O)O.C1[C@@H]([C@H]([C@@H](CN1)O)O)CO>>C1[C@@H]([C@H]([C@@H](CN1)O)O)CO.C(=O)([O-])[C@@H](O)[C@H](O)C(=O)[O-]
[O:1]=[C:2]([OH:3])[C@@H:4]([OH:5])[C@H:6]([OH:7])[C:8](=[O:9])[OH:10]>>[O:1]=[C:2]([O-:3])[C@@H:4]([OH:5])[C@H:6]([OH:7])[C:8](=[O:9])[O-:10]
O=C(O)[C@@H](O)[C@H](O)C(=O)O
O=C([O-])[C@@H](O)[C@H](O)C(=O)[O-]
null
null
O
Oxidation
OtherReaction
4af04878ecd22d61c6d7d46db52e672904d5e72408231940a5cea872324a16a2
4e878a1fdc9370141a3ed00507bdfaa037f36d163bb15c5076375a9835c80b8f
null
[O;D1;H0:1]=[C:2](-[OH;D1;+0:3])-[C:4]-[C:5]-[C:6](=[O;D1;H0:7])-[OH;D1;+0:8]>>[O-;H0;D1:8]-[C:6](=[O;D1;H0:7])-[C:5]-[C:4]-[C:2](-[O-;H0;D1:3])=[O;D1;H0:1]
98.9
[{"value": 98.0, "product": "C1[C@@H]([C@H]([C@@H](CN1)O)O)CO.C(=O)([O-])[C@@H](O)[C@H](O)C(=O)[O-]", "details": "PERCENTYIELD", "is_desired": false}, {"value": 98.9, "product": "C1[C@@H]([C@H]([C@@H](CN1)O)O)CO.C(=O)([O-])[C@@H](O)[C@H](O)C(=O)[O-]", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
10
MINUTE
A solution of D-(−)-tartaric acid (204 mg, 1.359 mmol) in deionized water (2.0 mL) was added into the solution of isofagomine (200 mg, 2.0 equivalents) dissolved in deionized water (2.0 mL) at room temperature. The solution was stirred for 10 min and lyophilized overnight. The residue was further dried under vacuum at ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Carboxylic acid
null
null
null
null
null
O
null
0.166667
O=C(O)[C@@H](O)[C@H](O)C(=O)O>O>O=C([O-])[C@@H](O)[C@H](O)C(=O)[O-]
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-bbb351fe6fd04e98bd244d8546e5d60e
C=C1C[C@@H](C(=O)OCC)[C@H](C(=O)OCC)C1>>C=C1C[C@@H](C(=O)O)[C@H](C(=O)OCC)C1
C(C)OC(=O)[C@H]1[C@@H](CC(C1)=C)C(=O)OCC.C([O-])([O-])=O.[K+].[K+].Cl>>C(C)OC(=O)[C@H]1[C@@H](CC(C1)=C)C(=O)O
CC[O:7][C:5]([C@@H:4]1[CH2:3][C:2](=[CH2:1])[CH2:14][C@H:8]1[C:9](=[O:10])[O:11][CH2:12][CH3:13])=[O:6]>>[CH2:1]=[C:2]1[CH2:3][C@@H:4]([C:5](=[O:6])[OH:7])[C@H:8]([C:9](=[O:10])[O:11][CH2:12][CH3:13])[CH2:14]1
C=C1C[C@@H](C(=O)OCC)[C@H](C(=O)OCC)C1
C=C1C[C@@H](C(=O)O)[C@H](C(=O)OCC)C1
null
null
O.CO
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
C=C1CCCC1
C-C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
49.1
[{"value": 49.1, "product": "C(C)OC(=O)[C@H]1[C@@H](CC(C1)=C)C(=O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A suspension of 20.0 g of trans-(1SR,2SR)-4-methylene-cyclopentane-1,2-dicarboxylic acid diethyl ester and 36.6 g of potassium carbonate in 200 ml of MeOH was heated at reflux temperature for 2 h. The mixture was cooled to 22°, diluted with 200 ml of water, the pH was adjusted to 2 using 80 ml of 25% HCl and the mixtur...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1CCCC1
Other
O.CO
null
null
C=C1C[C@@H](C(=O)OCC)[C@H](C(=O)OCC)C1>O.CO>C=C1C[C@@H](C(=O)O)[C@H](C(=O)OCC)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-874f0f7e20284885950217314592bb1d
C=C1C[C@@H](C(=O)O)[C@H](C(=O)OCC)C1.Nc1ccc(Cl)cc1>>C=C1C[C@@H](C(=O)Nc2ccc(Cl)cc2)[C@H](C(=O)OC)C1
OC1=CC=CC=2NN=NC21.Cl.CN(CCCN=C=NCC)C.C(C)OC(=O)[C@H]1[C@@H](CC(C1)=C)C(=O)O.ClC1=CC=C(N)C=C1>>COC(=O)[C@H]1[C@@H](CC(C1)=C)C(NC1=CC=C(C=C1)Cl)=O
C[CH2:19][O:18][C:16]([C@H:15]1[C@H:4]([C:5](O)=[O:6])[CH2:3][C:2](=[CH2:1])[CH2:20]1)=[O:17].[NH2:7][c:8]1[cH:9][cH:10][c:11]([Cl:12])[cH:13][cH:14]1>>[CH2:1]=[C:2]1[CH2:3][C@@H:4]([C:5](=[O:6])[NH:7][c:8]2[cH:9][cH:10][c:11]([Cl:12])[cH:13][cH:14]2)[C@H:15]([C:16](=[O:17])[O:18][CH3:19])[CH2:20]1
C=C1C[C@@H](C(=O)O)[C@H](C(=O)OCC)C1.Nc1ccc(Cl)cc1
C=C1C[C@@H](C(=O)Nc2ccc(Cl)cc2)[C@H](C(=O)OC)C1
null
null
CCN(CC)CC.CC#N
Acylation
OtherReaction
3bf28875ce940bec3ebc23b5f3bab0901f018435242045ff199b1dd7ca0bb2b3
bd93f76b28c347d49e1724c56040974bf1d3dcbde28ba19b6aa7c944fc5dd484
C=C1CC[C@H](C(=O)Nc2ccccc2)C1
C-[CH2;D2;+0:1]-[#8:2]-[C:3](=[O;D1;H0:4])-[C:5]-[C:6](-[C;H0;D3;+0:7](-O)=[O;D1;H0:8])-[C:9]-[C:10]=[C;D1;H2:11].[NH2;D1;+0:12]-[c:13](:[c:14]):[c:15]>>[C;D1;H2:11]=[C:10]-[C:9]-[C:6](-[C;H0;D3;+0:7](=[O;D1;H0:8])-[NH;D2;+0:12]-[c:13](:[c:14]):[c:15])-[C:5]-[C:3](=[O;D1;H0:4])-[#8:2]-[CH3;D1;+0:1]
55.4
[{"value": 55.4, "product": "COC(=O)[C@H]1[C@@H](CC(C1)=C)C(NC1=CC=C(C=C1)Cl)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
The crude mixture containing 1a (16.7 g) was dissolved in 500 ml of CH3CN and treated subsequently with 51 ml of NEt3, 25.0 g hydroxybenzotriazole and 31.3 g of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride and stirring was continued at 22° C. for 30 min. The mixture was treated with 23.1 g of 4-chloroan...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Ester.Primary amine
Ester.Secondary amide
null
null
C1CCCC1.c1ccccc1
HO-
CCN(CC)CC.CC#N
null
0.5
C=C1C[C@@H](C(=O)O)[C@H](C(=O)OCC)C1.Nc1ccc(Cl)cc1>CCN(CC)CC.CC#N>C=C1C[C@@H](C(=O)Nc2ccc(Cl)cc2)[C@H](C(=O)OC)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a779344bc4d8422e9828f1a68c0addd9
C=C1C[C@@H](C(=O)Nc2ccc(Cl)cc2)[C@H](C(=O)OC)C1>>C=C1C[C@@H](C(=O)O)[C@H](C(=O)Nc2ccc(Cl)cc2)C1
COC(=O)[C@H]1[C@@H](CC(C1)=C)C(NC1=CC=C(C=C1)Cl)=O>>ClC1=CC=C(C=C1)NC(=O)[C@H]1[C@@H](CC(C1)=C)C(=O)O
C[O:7][C:5](=[O:6])[C@H:8]1[C@H:4]([C:9](=[O:10])[NH:11][c:12]2[cH:13][cH:14][c:15]([Cl:16])[cH:17][cH:18]2)[CH2:3][C:2](=[CH2:1])[CH2:19]1>>[CH2:1]=[C:2]1[CH2:3][C@@H:4]([C:5](=[O:6])[OH:7])[C@H:8]([C:9](=[O:10])[NH:11][c:12]2[cH:13][cH:14][c:15]([Cl:16])[cH:17][cH:18]2)[CH2:19]1
C=C1C[C@@H](C(=O)Nc2ccc(Cl)cc2)[C@H](C(=O)OC)C1
C=C1C[C@@H](C(=O)O)[C@H](C(=O)Nc2ccc(Cl)cc2)C1
null
null
CO.[OH-].[Na+]
Miscellaneous
Ester saponification (methyl deprotection)
72bfc188ff30c9f80694ad619286ad6015a27c0992692c95fc6f33843ff64595
efff1c8096c49f5ffa3170381757d0670eba1ebba95c4daf05c233e5c1bbdf96
C=C1CC[C@H](C(=O)Nc2ccccc2)C1
C-[O;H0;D2;+0:1]-[C;H0;D3;+0:2](=[O;D1;H0:3])-[C@@H;D3;+0:4]1-[C:5]-[C:6](=[C;D1;H2:7])-[C:8]-[C@H;D3;+0:9]-1-[C;H0;D3;+0:10](=[O;D1;H0:11])-[#7:12]-[c:13]>>[C;D1;H2:7]=[C:6]1-[C:5]-[C@@H;D3;+0:4](-[C;H0;D3;+0:10](=[O;D1;H0:11])-[#7:12]-[c:13])-[C@H;D3;+0:9](-[C;H0;D3;+0:2](=[O;D1;H0:3])-[OH;D1;+0:1])-[C:8]-1
null
[]
null
null
null
null
The crude material 1b (13.7 g) was dissolved in 200 ml of MeOH and 20 ml of 7 N NaOH, the solution was stirred at 22° C. for 2 h and evaporated. The residue was partitioned between 0.1 N NaOH and CH2Cl2, the aqueous layer was washed with CH2Cl2 and the aqueous layer was acidified with 25% HCl, the suspension was filter...
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary amide
Carboxylic acid.Secondary amide
C1CCCC1
C1CCCC1
C1CCCC1.c1ccccc1
Other
CO.[OH-].[Na+]
null
null
C=C1C[C@@H](C(=O)Nc2ccc(Cl)cc2)[C@H](C(=O)OC)C1>CO.[OH-].[Na+]>C=C1C[C@@H](C(=O)O)[C@H](C(=O)Nc2ccc(Cl)cc2)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-948f02989d8747778707dea01672f602
C=C1C[C@@H](C(=O)O)[C@H](C(=O)OCC)C1.CC(C)(C)O.[N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1>>C=C1CC(NC(=O)OC(C)(C)C)C(C(=O)OC)C1
CC(C)(C)O.C(C)OC(=O)[C@H]1[C@@H](CC(C1)=C)C(=O)O.CCN(CC)CC.C1(=CC=CC=C1)P(=O)(C1=CC=CC=C1)N=[N+]=[N-]>>COC(=O)C1C(CC(C1)=C)NC(=O)OC(C)(C)C
C[CH2:17][O:16][C:14]([C@H:13]1[C@H:4]([C:6](O)=[O:7])[CH2:3][C:2](=[CH2:1])[CH2:18]1)=[O:15].[OH:8][C:9]([CH3:10])([CH3:11])[CH3:12].[N-]=[N+]=[N:5]P(=O)(c1ccccc1)c1ccccc1>>[CH2:1]=[C:2]1[CH2:3][CH:4]([NH:5][C:6](=[O:7])[O:8][C:9]([CH3:10])([CH3:11])[CH3:12])[CH:13]([C:14](=[O:15])[O:16][CH3:17])[CH2:18]1
C=C1C[C@@H](C(=O)O)[C@H](C(=O)OCC)C1.CC(C)(C)O.[N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
C=C1CC(NC(=O)OC(C)(C)C)C(C(=O)OC)C1
null
null
C1(=CC=CC=C1)C
Protection
OtherReaction
136944a1a3303309ac55275fa1a14b60cc0f29f5b963bb97b5c11e96d1e8c5b9
f2e92b5e20ec18885db87a01f7679b5ebb1cd68f65a21ea18ef3566f94514ce6
C=C1CCCC1
C-[CH2;D2;+0:1]-[#8:2]-[C:3](=[O;D1;H0:4])-[C@@H;D3;+0:5]1-[C:6]-[C:7](=[C;D1;H2:8])-[C:9]-[C@H;D3;+0:10]-1-[C;H0;D3;+0:11](-O)=[O;D1;H0:12].O=P(-[N;H0;D2;+0:13]=[N+]=[N-])(-c1:c:c:c:c:c:1)-c1:c:c:c:c:c:1.[C;D1;H3:14]-[C:15](-[C;D1;H3:16])(-[C;D1;H3:17])-[OH;D1;+0:18]>>[C;D1;H2:8]=[C:7]1-[C:6]-[CH;D3;+0:5](-[C:3](=[O;D...
59.3
[{"value": 55.0, "product": "COC(=O)C1C(CC(C1)=C)NC(=O)OC(C)(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 59.3, "product": "COC(=O)C1C(CC(C1)=C)NC(=O)OC(C)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
16
HOUR
To a solution of 2.03 g trans-(1SR,2SR)-4-methylene-cyclopentane-1,2-dicarboxylic acid ethyl ester (prepared and purified according to example 1 and 2, step 1) and 1.13 g of NEt3 in 25 ml of toluene was added drop wise at 22° C. 3.03 g of diphenylphosphoryl azide and the mixture was heated at 80° C. for 30 min. The mix...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Ester.Azide.Tertiary alcohol
Carbamic ester.Ester.Ether.Boc
C1CCCC1.c1ccccc1.c1ccccc1
C1CCCC1
C1CCCC1
HO-
C1(=CC=CC=C1)C
null
16
C=C1C[C@@H](C(=O)O)[C@H](C(=O)OCC)C1.CC(C)(C)O.[N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1>C1(=CC=CC=C1)C>C=C1CC(NC(=O)OC(C)(C)C)C(C(=O)OC)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-dd47680ab9c74cf5a2274334146045a8
C=C1CC(NC(=O)OC(C)(C)C)C(C(=O)OC)C1>>C=C1CC(NC(=O)OC(C)(C)C)C(C(=O)O)C1
COC(=O)C1C(CC(C1)=C)NC(=O)OC(C)(C)C.O[Li].O>>C(C)(C)(C)OC(=O)NC1C(CC(C1)=C)C(=O)O
C[O:16][C:14]([CH:13]1[CH:4]([NH:5][C:6](=[O:7])[O:8][C:9]([CH3:10])([CH3:11])[CH3:12])[CH2:3][C:2](=[CH2:1])[CH2:17]1)=[O:15]>>[CH2:1]=[C:2]1[CH2:3][CH:4]([NH:5][C:6](=[O:7])[O:8][C:9]([CH3:10])([CH3:11])[CH3:12])[CH:13]([C:14](=[O:15])[OH:16])[CH2:17]1
C=C1CC(NC(=O)OC(C)(C)C)C(C(=O)OC)C1
C=C1CC(NC(=O)OC(C)(C)C)C(C(=O)O)C1
null
null
O.CO
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
C=C1CCCC1
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
93.4
[{"value": 93.0, "product": "C(C)(C)(C)OC(=O)NC1C(CC(C1)=C)C(=O)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 93.4, "product": "C(C)(C)(C)OC(=O)NC1C(CC(C1)=C)C(=O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
To a solution of 1.28 g of 35a in 30 ml of MeOH was added a solution of 0.42 g of LiOH.H2O in 10 ml of H2O and stirring was continued at 50° C. for 1 h. The solution was evaporated to approximately half of the volume, the aqueous layer was washed with Et2O, acidified with HCl, the suspension was filtered and the residu...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1CCCC1
Other
O.CO
null
1
C=C1CC(NC(=O)OC(C)(C)C)C(C(=O)OC)C1>O.CO>C=C1CC(NC(=O)OC(C)(C)C)C(C(=O)O)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-42fa57afbabc4cbc93c9f7ca931f91b1
C=C1CC(NC(=O)OC(C)(C)C)C(C(=O)O)C1.Nc1ccc(Cl)cc1>>C=C1CC(NC(=O)OC(C)(C)C)C(C(=O)Nc2ccc(Cl)cc2)C1
C(C)(C)(C)OC(=O)NC1C(CC(C1)=C)C(=O)O.OC1=CC=CC=2NN=NC21.Cl.CN(CCCN=C=NCC)C.ClC1=CC=C(N)C=C1>>C(C)(C)(C)OC(NC1C(CC(C1)=C)C(NC1=CC=C(C=C1)Cl)=O)=O
O[C:14]([CH:13]1[CH:4]([NH:5][C:6](=[O:7])[O:8][C:9]([CH3:10])([CH3:11])[CH3:12])[CH2:3][C:2](=[CH2:1])[CH2:24]1)=[O:15].[NH2:16][c:17]1[cH:18][cH:19][c:20]([Cl:21])[cH:22][cH:23]1>>[CH2:1]=[C:2]1[CH2:3][CH:4]([NH:5][C:6](=[O:7])[O:8][C:9]([CH3:10])([CH3:11])[CH3:12])[CH:13]([C:14](=[O:15])[NH:16][c:17]2[cH:18][cH:19][...
C=C1CC(NC(=O)OC(C)(C)C)C(C(=O)O)C1.Nc1ccc(Cl)cc1
C=C1CC(NC(=O)OC(C)(C)C)C(C(=O)Nc2ccc(Cl)cc2)C1
null
null
CCN(CC)CC.C1CCOC1
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
C=C1CCC(C(=O)Nc2ccccc2)C1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4])-[C:5]-[C:6]=[C;D1;H2:7].[NH2;D1;+0:8]-[c:9](:[c:10]):[c:11]>>[C:4]-[C:3](-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:8]-[c:9](:[c:10]):[c:11])-[C:5]-[C:6]=[C;D1;H2:7]
64
[{"value": 64.0, "product": "C(C)(C)(C)OC(NC1C(CC(C1)=C)C(NC1=CC=C(C=C1)Cl)=O)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 64.0, "product": "C(C)(C)(C)OC(NC1C(CC(C1)=C)C(NC1=CC=C(C=C1)Cl)=O)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
16
HOUR
A stirred solution of 1.085 g of 35b in 10 ml of THF was treated subsequently with 1.25 ml of NEt3, 0.69 g hydroxybenzotriazole, 1.21 g of N-(3-dimethylaminopropyl)-N′-ethylcarbodiimide hydrochloride and 0.63 g of 4-chloroaniline and stirring was continued at 22° C. for 16 h. The mixture was evaporated and the residue ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
C1CCCC1.c1ccccc1
HO-
CCN(CC)CC.C1CCOC1
null
16
C=C1CC(NC(=O)OC(C)(C)C)C(C(=O)O)C1.Nc1ccc(Cl)cc1>CCN(CC)CC.C1CCOC1>C=C1CC(NC(=O)OC(C)(C)C)C(C(=O)Nc2ccc(Cl)cc2)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-16ea1b0ba91649e1816daa82899cc1c5
C=C1CC(NC(=O)OC(C)(C)C)C(C(=O)Nc2ccc(Cl)cc2)C1>>C=C1CC(N)C(C(=O)Nc2ccc(Cl)cc2)C1
C(C)(C)(C)OC(NC1C(CC(C1)=C)C(NC1=CC=C(C=C1)Cl)=O)=O>>ClC1=CC=C(C=C1)NC(=O)C1C(CC(C1)=C)N
CC(C)(C)OC(=O)[NH:5][CH:4]1[CH2:3][C:2](=[CH2:1])[CH2:17][CH:6]1[C:7](=[O:8])[NH:9][c:10]1[cH:11][cH:12][c:13]([Cl:14])[cH:15][cH:16]1>>[CH2:1]=[C:2]1[CH2:3][CH:4]([NH2:5])[CH:6]([C:7](=[O:8])[NH:9][c:10]2[cH:11][cH:12][c:13]([Cl:14])[cH:15][cH:16]2)[CH2:17]1
C=C1CC(NC(=O)OC(C)(C)C)C(C(=O)Nc2ccc(Cl)cc2)C1
C=C1CC(N)C(C(=O)Nc2ccc(Cl)cc2)C1
null
null
FC(C(=O)O)(F)F.C(Cl)Cl
Reduction
Hydrogenolysis of amides/imides/carbamates
3c33dd2a2d355ee5ba0287367e209aa147a39aa00607f0c95fb2bf1ade45d014
c5b5dffe7dd8beebdc1baa8b5b05300a9f7079e65dcfd42ade6f8a77ff09537d
C=C1CCC(C(=O)Nc2ccccc2)C1
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C:2](-[C:3]-[C:4]=[C;D1;H2:5])-[C:6]-[C:7](-[#7:8])=[O;D1;H0:9]>>[#7:8]-[C:7](=[O;D1;H0:9])-[C:6]-[C:2](-[NH2;D1;+0:1])-[C:3]-[C:4]=[C;D1;H2:5]
69
[{"value": 69.0, "product": "ClC1=CC=C(C=C1)NC(=O)C1C(CC(C1)=C)N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 68.5, "product": "ClC1=CC=C(C=C1)NC(=O)C1C(CC(C1)=C)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 0.98 g of 35c in 10 ml of CH2Cl2 and 1.07 ml of trifluoroacetic acid was stirred at 22° C. for 2 h. The solution was evaporated and the residue partitioned between H2O and CH2Cl2. The aqueous layer was treated slowly with NaHCO3 until pH═8, the suspension was filtered, the residue washed with H2O and drie...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Primary amine
null
null
C1CCCC1.c1ccccc1
HO-
FC(C(=O)O)(F)F.C(Cl)Cl
null
null
C=C1CC(NC(=O)OC(C)(C)C)C(C(=O)Nc2ccc(Cl)cc2)C1>FC(C(=O)O)(F)F.C(Cl)Cl>C=C1CC(N)C(C(=O)Nc2ccc(Cl)cc2)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3687e99f63a84a9f816ec4bb068d0c28
O=C(O)c1ccc(Br)cc1F.Oc1ccccn1>>O=C(O)c1ccc(-n2ccccc2=O)cc1F
BrC1=CC(=C(C(=O)O)C=C1)F.OC1=NC=CC=C1.OC=1C=CC=C2C=CC=NC12.C(=O)([O-])[O-].[K+].[K+]>>FC1=C(C(=O)O)C=CC(=C1)N1C(C=CC=C1)=O
Br[c:7]1[cH:6][cH:5][c:4]([C:2](=[O:1])[OH:3])[c:16]([F:17])[cH:15]1.[n:8]1[cH:9][cH:10][cH:11][cH:12][c:13]1[OH:14]>>[O:1]=[C:2]([OH:3])[c:4]1[cH:5][cH:6][c:7](-[n:8]2[cH:9][cH:10][cH:11][cH:12][c:13]2=[O:14])[cH:15][c:16]1[F:17]
O=C(O)c1ccc(Br)cc1F.Oc1ccccn1
O=C(O)c1ccc(-n2ccccc2=O)cc1F
null
null
O.CS(=O)C
Acylation
OtherReaction
4308b383a3710ca54de2d883c53ac81bae07d58b1e4603761dc4ccecde83005c
9fb0a4734c628f8028aa0d8a5f3520861ccd6e9f72791fbc28874467838ebc37
O=c1ccccn1-c1ccccc1
Br-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[OH;D1;+0:6]-[c;H0;D3;+0:7]1:[c:8]:[c:9]:[c:10]:[c:11]:[n;H0;D2;+0:12]:1>>[O;H0;D1;+0:6]=[c;H0;D3;+0:7]1:[c:8]:[c:9]:[c:10]:[c:11]:[n;H0;D3;+0:12]:1-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5]
49.4
[{"value": 49.4, "product": "FC1=C(C(=O)O)C=CC(=C1)N1C(C=CC=C1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
150
CELSIUS
null
null
To a solution of 10.96 g of 4-bromo-2-fluoro-benzoic acid in 40 ml of DMSO was added subsequently 6.67 g of 2-hydroxypyridine, 1.10 g of 8-hydroxyquinoline, 1.43 g of Cu(I)I and 7.61 g of K2CO3 and the mixture was heated to 150° C. for 18 h. The suspension was diluted with water, filtered, the residue was washed with A...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
null
c1ccccc1.c1ccncc1
c1ccccc1.c1ccncc1
c1ccccc1.c1ccncc1
HBr
O.CS(=O)C
150
null
O=C(O)c1ccc(Br)cc1F.Oc1ccccn1>O.CS(=O)C>O=C(O)c1ccc(-n2ccccc2=O)cc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a1cc029d64cf4cc0906cc80cbeb6081b
C=C1CC(N)C(C(=O)Nc2ccc(Cl)cc2)C1.O=C(O)c1ccc(-n2ccccc2=O)cc1F>>C=C1CC(NC(=O)c2ccc(-n3ccccc3=O)cc2F)C(C(=O)Nc2ccc(Cl)cc2)C1
ClC1=CC=C(C=C1)NC(=O)C1C(CC(C1)=C)N.FC1=C(C(=O)O)C=CC(=C1)N1C(C=CC=C1)=O>>ClC1=CC=C(C=C1)NC(=O)C1C(CC(C1)=C)NC(C1=C(C=C(C=C1)N1C(C=CC=C1)=O)F)=O
[CH2:1]=[C:2]1[CH2:3][CH:4]([NH2:5])[CH:22]([C:23](=[O:24])[NH:25][c:26]2[cH:27][cH:28][c:29]([Cl:30])[cH:31][cH:32]2)[CH2:33]1.O[C:6](=[O:7])[c:8]1[cH:9][cH:10][c:11](-[n:12]2[cH:13][cH:14][cH:15][cH:16][c:17]2=[O:18])[cH:19][c:20]1[F:21]>>[CH2:1]=[C:2]1[CH2:3][CH:4]([NH:5][C:6](=[O:7])[c:8]2[cH:9][cH:10][c:11](-[n:12...
C=C1CC(N)C(C(=O)Nc2ccc(Cl)cc2)C1.O=C(O)c1ccc(-n2ccccc2=O)cc1F
C=C1CC(NC(=O)c2ccc(-n3ccccc3=O)cc2F)C(C(=O)Nc2ccc(Cl)cc2)C1
null
null
null
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
C=C1CC(NC(=O)c2ccc(-n3ccccc3=O)cc2)C(C(=O)Nc2ccccc2)C1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[#7:6]-[C:7](=[O;D1;H0:8])-[C:9]-[C:10](-[NH2;D1;+0:11])-[C:12]-[C:13]=[C;D1;H2:14]>>[#7:6]-[C:7](=[O;D1;H0:8])-[C:9]-[C:10](-[NH;D2;+0:11]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5])-[C:12]-[C:13]=[C;D1;H2:14]
69
[{"value": 69.0, "product": "ClC1=CC=C(C=C1)NC(=O)C1C(CC(C1)=C)NC(C1=C(C=C(C=C1)N1C(C=CC=C1)=O)F)=O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Starting from 35d and 35e, the title compound was prepared in 69% yield according to the procedure for example 1 and 2, step 2. MS: 466.3 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
C1CCCC1.c1ccccc1.c1ccncc1.c1ccccc1
HO-
null
null
null
C=C1CC(N)C(C(=O)Nc2ccc(Cl)cc2)C1.O=C(O)c1ccc(-n2ccccc2=O)cc1F>>C=C1CC(NC(=O)c2ccc(-n3ccccc3=O)cc2F)C(C(=O)Nc2ccc(Cl)cc2)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9171da76c4674278a26445b9f01b58ab
C=C1C[C@@H](C(=O)OCC)[C@H](C(=O)OCC)C1>>C=C1C[C@H](C(=O)OCC)[C@@H](C(=O)OCC)C1
[OH-].[Na+].C(C)OC(=O)[C@H]1[C@@H](CC(C1)=C)C(=O)OCC.P(=O)([O-])([O-])[O-].[K+].[K+].[K+].[Na+].[Cl-]>>C(C)OC(=O)[C@@H]1[C@H](CC(C1)=C)C(=O)OCC
[CH2:1]=[C:2]1[CH2:3][C@@H:4]([C:5](=[O:6])[O:7][CH2:8][CH3:9])[C@H:10]([C:11](=[O:12])[O:13][CH2:14][CH3:15])[CH2:16]1>>[CH2:1]=[C:2]1[CH2:3][C@H:4]([C:5](=[O:6])[O:7][CH2:8][CH3:9])[C@@H:10]([C:11](=[O:12])[O:13][CH2:14][CH3:15])[CH2:16]1
C=C1C[C@@H](C(=O)OCC)[C@H](C(=O)OCC)C1
C=C1C[C@H](C(=O)OCC)[C@@H](C(=O)OCC)C1
null
null
null
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
C=C1CCCC1
null
44.5
[{"value": 44.5, "product": "C(C)OC(=O)[C@@H]1[C@H](CC(C1)=C)C(=O)OCC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
7
CELSIUS
null
null
An emulsion of 1.1 g racemic trans-4-Methylene-cyclopentane-1,2-dicarboxylic acid diethyl ester (Merck 8.14188.0010) in an aqueous buffer (potassium phosphate 5 mM, NaCl 0.1 M) was adjusted to pH 7.0. Under stirring at 7° C. the hydrolysis was performed with 14 mg lipase PN from Phycomyces nitens [Wako Chemicals GmbH N...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
C1CCCC1
null
null
7
null
C=C1C[C@@H](C(=O)OCC)[C@H](C(=O)OCC)C1>>C=C1C[C@H](C(=O)OCC)[C@@H](C(=O)OCC)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-34aaaf9b7bff4c39818c9297ecafd186
C=C1C[C@H](C(=O)OCC)[C@@H](C(=O)OCC)C1>>C=C1C[C@H](C(=O)O)[C@@H](C(=O)OCC)C1
[OH-].[Na+].C(C)OC(=O)[C@@H]1[C@H](CC(C1)=C)C(=O)OCC.P(=O)([O-])([O-])[O-].[K+].[K+].[K+].[Na+].[Cl-]>>C(C)OC(=O)[C@@H]1[C@H](CC(C1)=C)C(=O)O
CC[O:7][C:5]([C@H:4]1[CH2:3][C:2](=[CH2:1])[CH2:14][C@@H:8]1[C:9](=[O:10])[O:11][CH2:12][CH3:13])=[O:6]>>[CH2:1]=[C:2]1[CH2:3][C@H:4]([C:5](=[O:6])[OH:7])[C@@H:8]([C:9](=[O:10])[O:11][CH2:12][CH3:13])[CH2:14]1
C=C1C[C@H](C(=O)OCC)[C@@H](C(=O)OCC)C1
C=C1C[C@H](C(=O)O)[C@@H](C(=O)OCC)C1
null
null
null
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
C=C1CCCC1
C-C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
86
[{"value": 86.0, "product": "C(C)OC(=O)[C@@H]1[C@H](CC(C1)=C)C(=O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
An emulsion of 1.7 g 41a in an aqueous buffer (potassium phosphate 3 mM, NaCl 0.1 M) was adjusted to pH 7.5. Under stirring at room temperature the hydrolysis was performed with 15 mg lipase OF from Candida rugosa under pH control (pH-static, 1M NaOH). After consumption of 6.5 ml 1M NaOH solution and 7 h the reaction m...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1CCCC1
Other
null
null
null
C=C1C[C@H](C(=O)OCC)[C@@H](C(=O)OCC)C1>>C=C1C[C@H](C(=O)O)[C@@H](C(=O)OCC)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f785e51d06b84c14b68035a34ef9de19
C=C1C[C@H](C(=O)O)[C@@H](C(=O)OCC)C1.Nc1ccc(-n2ccccc2=O)cc1F>>C=C1C[C@H](C(=O)Nc2ccc(-n3ccccc3=O)cc2F)[C@@H](C(=O)OCC)C1
C(C)OC(=O)[C@@H]1[C@H](CC(C1)=C)C(=O)O.ClC(=O)OCC(C)C.NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F>>C(C)OC(=O)[C@@H]1[C@H](CC(C1)=C)C(NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F)=O
O[C:5]([C@H:4]1[CH2:3][C:2](=[CH2:1])[CH2:28][C@@H:22]1[C:23](=[O:24])[O:25][CH2:26][CH3:27])=[O:6].[NH2:7][c:8]1[cH:9][cH:10][c:11](-[n:12]2[cH:13][cH:14][cH:15][cH:16][c:17]2=[O:18])[cH:19][c:20]1[F:21]>>[CH2:1]=[C:2]1[CH2:3][C@H:4]([C:5](=[O:6])[NH:7][c:8]2[cH:9][cH:10][c:11](-[n:12]3[cH:13][cH:14][cH:15][cH:16][c:1...
C=C1C[C@H](C(=O)O)[C@@H](C(=O)OCC)C1.Nc1ccc(-n2ccccc2=O)cc1F
C=C1C[C@H](C(=O)Nc2ccc(-n3ccccc3=O)cc2F)[C@@H](C(=O)OCC)C1
null
null
CN(C)C=O.CN1CCOCC1.C1CCOC1
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
C=C1CC[C@@H](C(=O)Nc2ccc(-n3ccccc3=O)cc2)C1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4]-[C:5](-[#8:6])=[O;D1;H0:7])-[C:8]-[C:9]=[C;D1;H2:10].[NH2;D1;+0:11]-[c:12](:[c:13]):[c:14]>>[#8:6]-[C:5](=[O;D1;H0:7])-[C:4]-[C:3](-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:11]-[c:12](:[c:13]):[c:14])-[C:8]-[C:9]=[C;D1;H2:10]
66
[{"value": 66.0, "product": "C(C)OC(=O)[C@@H]1[C@H](CC(C1)=C)C(NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
To a solution of 1.0 g of 41b in 10 ml of THF and 0.61 ml of N-methylmorpholine was added at −12° C. 0.72 ml of isobutyl chloroformate and stirring was continued at −15° C. for 30 min and at 20° C. for 1 h. The suspension obtained was added to a hot (60° C.) solution of 1.13 g of 1-(4-amino-3-fluoro-phenyl)-1H-pyridin-...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
C1CCCC1.c1ccccc1.c1ccncc1
HO-
CN(C)C=O.CN1CCOCC1.C1CCOC1
null
1
C=C1C[C@H](C(=O)O)[C@@H](C(=O)OCC)C1.Nc1ccc(-n2ccccc2=O)cc1F>CN(C)C=O.CN1CCOCC1.C1CCOC1>C=C1C[C@H](C(=O)Nc2ccc(-n3ccccc3=O)cc2F)[C@@H](C(=O)OCC)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ebd3d6c044f84cc9a66afcd766b68400
Nc1ccc(Cl)cc1.O=C1C=CC(=O)O1>>O=C(O)/C=C\C(=O)Nc1ccc(Cl)cc1
C1(\C=C/C(=O)O1)=O.ClC1=CC=C(N)C=C1>>ClC1=CC=C(C=C1)NC(=O)\C=C/C(=O)O
[NH2:8][c:9]1[cH:10][cH:11][c:12]([Cl:13])[cH:14][cH:15]1.[O:1]=[C:2]1[O:3][C:6](=[O:7])[CH:5]=[CH:4]1>>[O:1]=[C:2]([OH:3])/[CH:4]=[CH:5]\[C:6](=[O:7])[NH:8][c:9]1[cH:10][cH:11][c:12]([Cl:13])[cH:14][cH:15]1
Nc1ccc(Cl)cc1.O=C1C=CC(=O)O1
O=C(O)/C=C\C(=O)Nc1ccc(Cl)cc1
null
null
C(C)#N
Acylation
OtherReaction
167c64d23e09803118fc6a0c2e419ae61f1d34b060caa5549f619df29edcd65f
babc03c287bd8cfa2865fae168af372e93ed67f910f700d8b87af94362c61841
c1ccccc1
[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4].[O;D1;H0:5]=[C:6]1-[C:7]=[C:8]-[C;H0;D3;+0:9](=[O;D1;H0:10])-[O;H0;D2;+0:11]-1>>[O;D1;H0:5]=[C:6](-[OH;D1;+0:11])/[C:7]=[C:8]\[C;H0;D3;+0:9](=[O;D1;H0:10])-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4]
97.1
[{"value": 97.0, "product": "ClC1=CC=C(C=C1)NC(=O)\\C=C/C(=O)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 97.1, "product": "ClC1=CC=C(C=C1)NC(=O)\\C=C/C(=O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
24
HOUR
A solution of 29.3 g (300 mmol) of maleic anhydride in 500 ml of acetonitrile was treated portionwise with 40 g (310 mmol) of 4-chloroaniline and stirred at room temperature during 24 hrs. The thick precipitate that had formed was filtered off, washed with cold acetonitrile and dried i.v. to yield 65.7 g (97%)of the ti...
10.6084/m9.figshare.5104873.v1
null
Anhydride.Primary amine
Carboxylic acid.Secondary amide
C1=CCOC1
null
c1ccccc1
null
C(C)#N
null
24
Nc1ccc(Cl)cc1.O=C1C=CC(=O)O1>C(C)#N>O=C(O)/C=C\C(=O)Nc1ccc(Cl)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-befc109c4e5b4818a83415c21aacd7d1
O=C(O)/C=C\C(=O)Nc1ccc(Cl)cc1>>O=C1C=CC(=O)N1c1ccc(Cl)cc1
ClC1=CC=C(C=C1)NC(=O)\C=C/C(=O)O.C[Si](C)(C)N[Si](C)(C)C.Cl>>ClC1=CC=C(C=C1)N1C(C=CC1=O)=O
O[C:2](=[O:1])/[CH:3]=[CH:4]\[C:5](=[O:6])[NH:7][c:8]1[cH:9][cH:10][c:11]([Cl:12])[cH:13][cH:14]1>>[O:1]=[C:2]1[CH:3]=[CH:4][C:5](=[O:6])[N:7]1[c:8]1[cH:9][cH:10][c:11]([Cl:12])[cH:13][cH:14]1
O=C(O)/C=C\C(=O)Nc1ccc(Cl)cc1
O=C1C=CC(=O)N1c1ccc(Cl)cc1
null
[Cl-].[Cl-].[Zn+2]
C1=CC=CC=C1
Miscellaneous
OtherReaction
fecf48c59be3cbdc0ce087b20e9fa269ee3fcac32445ce272bbdc89102043fe7
48e6b2b999f3f15ec39998545386900040317bcbdbb4347c7e2886995a8c9772
O=C1C=CC(=O)N1c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])/[C:3]=[C:4]\[C:5](=[O;D1;H0:6])-[NH;D2;+0:7]-[c:8](:[c:9]):[c:10]>>[O;D1;H0:2]=[C;H0;D3;+0:1]1-[C:3]=[C:4]-[C:5](=[O;D1;H0:6])-[N;H0;D3;+0:7]-1-[c:8](:[c:9]):[c:10]
97
[{"value": 97.0, "product": "ClC1=CC=C(C=C1)N1C(C=CC1=O)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 97.0, "product": "ClC1=CC=C(C=C1)N1C(C=CC1=O)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
In Analogy to the procedure given in Mhaske et al., Synthesis, 2003, p863-870: A solution of 65 g (288 mmol) of (Z)-3-(4-chloro-phenylcarbamoyl)-acrylic acid in 300 ml of benzene was treated with 41.2 g (302 mmol) of zinc dichloride, dropwise with 90.1 ml (432 mmol) of bis(trimethylsilyl)amine and refluxed during 5 hrs...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amide
Substituted dicarboximide
null
C1=CC[NH]C1
C1=CC[NH]C1.c1ccccc1
HO-
[Cl-].[Cl-].[Zn+2].C1=CC=CC=C1
null
null
O=C(O)/C=C\C(=O)Nc1ccc(Cl)cc1>[Cl-].[Cl-].[Zn+2].C1=CC=CC=C1>O=C1C=CC(=O)N1c1ccc(Cl)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-01f24a38bb21480da8e3ab11a692e97a
CCOC(=O)C=[N+]=[N-].O=C1C=CC(=O)N1c1ccc(Cl)cc1>>CCOC(=O)C1C2C(=O)N(c3ccc(Cl)cc3)C(=O)C12
ClC1=CC=C(C=C1)N1C(C=CC1=O)=O.C(C)OC(C=[N+]=[N-])=O>>C(C)OC(=O)C1C2C(N(C(C12)=O)C1=CC=C(C=C1)Cl)=O
[N-]=[N+]=[CH:6][C:4]([O:3][CH2:2][CH3:1])=[O:5].[CH:7]1=[CH:20][C:18](=[O:19])[N:10]([c:11]2[cH:12][cH:13][c:14]([Cl:15])[cH:16][cH:17]2)[C:8]1=[O:9]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]1[CH:7]2[C:8](=[O:9])[N:10]([c:11]3[cH:12][cH:13][c:14]([Cl:15])[cH:16][cH:17]3)[C:18](=[O:19])[CH:20]12
CCOC(=O)C=[N+]=[N-].O=C1C=CC(=O)N1c1ccc(Cl)cc1
CCOC(=O)C1C2C(=O)N(c3ccc(Cl)cc3)C(=O)C12
null
null
C=1(C(=CC=CC1)C)C
C-C Coupling
OtherReaction
b3907611f56aaaea5fdd12ab720953c488457938f885c7a1795c4bfd7a1a2e67
2bf044f9aa3102f7e58ada063c1d8beb18b3b23505b944ca768ff7e6f4f49661
O=C1C2CC2C(=O)N1c1ccccc1
[C:1]-[#8:2]-[C:3](=[O;D1;H0:4])-[CH;D2;+0:5]=[N+]=[N-].[O;D1;H0:6]=[C:7]1-[CH;D2;+0:8]=[CH;D2;+0:9]-[C:10](=[O;D1;H0:11])-[#7:12]-1-[c:13]>>[C:1]-[#8:2]-[C:3](=[O;D1;H0:4])-[CH;D3;+0:5]1-[CH;D3;+0:8]2-[C:7](=[O;D1;H0:6])-[#7:12](-[c:13])-[C:10](=[O;D1;H0:11])-[CH;D3;+0:9]-2-1
35
[{"value": 35.0, "product": "C(C)OC(=O)C1C2C(N(C(C12)=O)C1=CC=C(C=C1)Cl)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 34.8, "product": "C(C)OC(=O)C1C2C(N(C(C12)=O)C1=CC=C(C=C1)Cl)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 19.4 g (93 mmol) of 1-(4-chloro-phenyl)-pyrrole-2,5-dione in 120 ml of xylene was treated with 19.4 ml (187 mmol) of ethyldiazoacetate and refluxed during 12 hrs. Evaporation of the solvent and chromatography on silica gel with toluene and then a gradient of toluene/AcOEt from 95:5 to 90:10 gave 9.5 g(35%...
10.6084/m9.figshare.5104873.v1
null
Ester.Diazo
Ester
C1=CC[NH]C1
C1[NH]CC2CC12
C1[NH]CC2CC12.c1ccccc1
Other
C=1(C(=CC=CC1)C)C
null
null
CCOC(=O)C=[N+]=[N-].O=C1C=CC(=O)N1c1ccc(Cl)cc1>C=1(C(=CC=CC1)C)C>CCOC(=O)C1C2C(=O)N(c3ccc(Cl)cc3)C(=O)C12
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f0500249342f437da4972a50b3c26b60
CCOC(=O)C1C2C(=O)N(c3ccc(Cl)cc3)C(=O)C12.Nc1ccc(-n2ccccc2=O)cc1F>>CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
Cl.C(C)OC(=O)C1C2C(N(C(C12)=O)C1=CC=C(C=C1)Cl)=O.C[Si](C)(C)[N-][Si](C)(C)C.[Li+].NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F>>C(C)OC(=O)C1C(C1C(NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F)=O)C(NC1=CC=C(C=C1)Cl)=O
[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]1[CH:7]2[C:8](=[O:9])[N:10]([c:11]3[cH:12][cH:13][c:14]([Cl:15])[cH:16][cH:17]3)[C:19](=[O:20])[CH:18]12.[NH2:21][c:22]1[cH:23][cH:24][c:25](-[n:26]2[cH:27][cH:28][cH:29][cH:30][c:31]2=[O:32])[cH:33][c:34]1[F:35]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]1[CH:7]([C:8](=[O:9])[NH:10][c...
CCOC(=O)C1C2C(=O)N(c3ccc(Cl)cc3)C(=O)C12.Nc1ccc(-n2ccccc2=O)cc1F
CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
null
null
C1CCOC1
Acylation
OtherReaction
54a0d6b7a6245a7cbbf3baeb2a511e2b626ea0970d3987a3f1bccd4c1e2a148f
c5dbbff33268430c8bfa22331d710773ca50cd979a5fb6dcb4356e0495eb059b
O=C(Nc1ccccc1)C1CC1C(=O)Nc1ccc(-n2ccccc2=O)cc1
[#8:1]-[C:2](=[O;D1;H0:3])-[C:4]1-[C:5]2-[C:6]-1-[C:7](=[O;D1;H0:8])-[N;H0;D3;+0:9](-[c:10](:[c:11]):[c:12])-[C;H0;D3;+0:13]-2=[O;D1;H0:14].[NH2;D1;+0:15]-[c:16](:[c:17]):[c:18]>>[#8:1]-[C:2](=[O;D1;H0:3])-[C:4]1-[C:5](-[C;H0;D3;+0:13](=[O;D1;H0:14])-[NH;D2;+0:15]-[c:16](:[c:17]):[c:18])-[C:6]-1-[C:7](=[O;D1;H0:8])-[NH...
24
[{"value": 24.0, "product": "C(C)OC(=O)C1C(C1C(NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F)=O)C(NC1=CC=C(C=C1)Cl)=O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
A solution of 7 g (34 mmol) of 1-(4-amino-3-fluoro-phenyl)-1H-pyridin-2-one (prepared according to C. F. Bigge et al., patent application WO 2003045912) in 25 ml of THF was cooled to −78° C. and treated dropwise with 41 ml of a 1M lithium bis(trimethylsilyl)amide-solution in THF and stirred for 30 min. To this solution...
10.6084/m9.figshare.5104873.v1
null
Substituted dicarboximide.Primary amine
Secondary amide.Secondary amide
C1[NH]CC2CC12
null
C1CC1.c1ccccc1.c1ccccc1.c1ccncc1
null
C1CCOC1
null
0.5
CCOC(=O)C1C2C(=O)N(c3ccc(Cl)cc3)C(=O)C12.Nc1ccc(-n2ccccc2=O)cc1F>C1CCOC1>CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-576a1ea47e45462dad2e5c13b42a3598
CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccccc2=O)cc1F>>O=C(O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
Cl.C(C)OC(=O)C1C(C1C(NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F)=O)C(NC1=CC=C(C=C1)Cl)=O.[Li+].[OH-]>>ClC1=CC=C(C=C1)NC(=O)C1C(C1C(NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F)=O)C(=O)O
CC[O:3][C:2](=[O:1])[CH:4]1[CH:5]([C:6](=[O:7])[NH:8][c:9]2[cH:10][cH:11][c:12]([Cl:13])[cH:14][cH:15]2)[CH:16]1[C:17](=[O:18])[NH:19][c:20]1[cH:21][cH:22][c:23](-[n:24]2[cH:25][cH:26][cH:27][cH:28][c:29]2=[O:30])[cH:31][c:32]1[F:33]>>[O:1]=[C:2]([OH:3])[CH:4]1[CH:5]([C:6](=[O:7])[NH:8][c:9]2[cH:10][cH:11][c:12]([Cl:13...
CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
O=C(O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
null
null
C1CCOC1
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(Nc1ccccc1)C1CC1C(=O)Nc1ccc(-n2ccccc2=O)cc1
C-C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
86.5
[{"value": 86.0, "product": "ClC1=CC=C(C=C1)NC(=O)C1C(C1C(NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F)=O)C(=O)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 86.5, "product": "ClC1=CC=C(C=C1)NC(=O)C1C(C1C(NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F)=O)C(=O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
A solution of 80 mg (0.16 mmol) of (1RS,2RS,3SR)-2-(4-chloro-phenylcarbamoyl)-3-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenylcarbamoyl]-cyclopropanecarboxylic acid ethyl ester (example 68) in a mixture of 10 ml of THF and 10 ml of a 1M aqueous LiOH-solution was stirred during 2 hrs at room temperature. The mixture was pou...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1CC1.c1ccccc1.c1ccccc1.c1ccncc1
Other
C1CCOC1
null
2
CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccccc2=O)cc1F>C1CCOC1>O=C(O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-443283d1e67e46c58576fc7b5ca5ccaa
C=C1C[C@H](C(=O)O)[C@@H](C(=O)OCC)C1.Nc1ccc(Cl)cn1>>C=C1C[C@H](C(=O)Nc2ccc(Cl)cn2)[C@@H](C(=O)OCC)C1
C(C)OC(=O)[C@@H]1[C@H](CC(C1)=C)C(=O)O.NC1=NC=C(C=C1)Cl>>C(C)OC(=O)[C@@H]1[C@H](CC(C1)=C)C(NC1=NC=C(C=C1)Cl)=O
O[C:5]([C@H:4]1[CH2:3][C:2](=[CH2:1])[CH2:21][C@@H:15]1[C:16](=[O:17])[O:18][CH2:19][CH3:20])=[O:6].[NH2:7][c:8]1[cH:9][cH:10][c:11]([Cl:12])[cH:13][n:14]1>>[CH2:1]=[C:2]1[CH2:3][C@H:4]([C:5](=[O:6])[NH:7][c:8]2[cH:9][cH:10][c:11]([Cl:12])[cH:13][n:14]2)[C@@H:15]([C:16](=[O:17])[O:18][CH2:19][CH3:20])[CH2:21]1
C=C1C[C@H](C(=O)O)[C@@H](C(=O)OCC)C1.Nc1ccc(Cl)cn1
C=C1C[C@H](C(=O)Nc2ccc(Cl)cn2)[C@@H](C(=O)OCC)C1
null
null
null
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
C=C1CC[C@@H](C(=O)Nc2ccccn2)C1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4]-[C:5](-[#8:6])=[O;D1;H0:7])-[C:8]-[C:9]=[C;D1;H2:10].[NH2;D1;+0:11]-[c:12](:[c:13]):[#7;a:14]:[c:15]>>[#8:6]-[C:5](=[O;D1;H0:7])-[C:4]-[C:3](-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:11]-[c:12](:[c:13]):[#7;a:14]:[c:15])-[C:8]-[C:9]=[C;D1;H2:10]
48
[{"value": 48.0, "product": "C(C)OC(=O)[C@@H]1[C@H](CC(C1)=C)C(NC1=NC=C(C=C1)Cl)=O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Starting from 41b, the title compound was prepared in 48% yield according to the procedure for example 1 and 2, step 2 using 2-amino-5-chloropyridine. MS: 309.1 (M+H)+. Conditions: See reaction.notes.procedure_details.
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
C1CCCC1.c1ccncc1
HO-
null
null
null
C=C1C[C@H](C(=O)O)[C@@H](C(=O)OCC)C1.Nc1ccc(Cl)cn1>>C=C1C[C@H](C(=O)Nc2ccc(Cl)cn2)[C@@H](C(=O)OCC)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d81b8457cb9e443291174a14e7f153ee
CO.O=C(O)C1C(C(=O)Nc2ccc(-n3ccccc3=O)cc2F)C1c1ccccc1>>COC(=O)C1C(C(=O)Nc2ccc(-n3ccccc3=O)cc2F)C1c1ccccc1
FC1=C(C=CC(=C1)N1C(C=CC=C1)=O)NC(=O)C1C(C1C1=CC=CC=C1)C(=O)O.S(=O)(Cl)Cl.CO>>COC(=O)C1C(C1C1=CC=CC=C1)C(NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F)=O
[CH3:1][OH:2].O[C:3](=[O:4])[CH:5]1[CH:6]([C:7](=[O:8])[NH:9][c:10]2[cH:11][cH:12][c:13](-[n:14]3[cH:15][cH:16][cH:17][cH:18][c:19]3=[O:20])[cH:21][c:22]2[F:23])[CH:24]1[c:25]1[cH:26][cH:27][cH:28][cH:29][cH:30]1>>[CH3:1][O:2][C:3](=[O:4])[CH:5]1[CH:6]([C:7](=[O:8])[NH:9][c:10]2[cH:11][cH:12][c:13](-[n:14]3[cH:15][cH:1...
CO.O=C(O)C1C(C(=O)Nc2ccc(-n3ccccc3=O)cc2F)C1c1ccccc1
COC(=O)C1C(C(=O)Nc2ccc(-n3ccccc3=O)cc2F)C1c1ccccc1
null
null
null
Protection
Esterification of Carboxylic Acids
9cecdbd189c6f9c3648521d17154d013842a5498de4e76e65efb1d842973340b
af0b8064f2e82ebe66c4c29d2391785ac1b993104265ccdc4d67ca79e36fa3c8
O=C(Nc1ccc(-n2ccccc2=O)cc1)C1CC1c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]1-[C:4]-[C:5]-1-[C:6](-[#7:7])=[O;D1;H0:8].[C;D1;H3:9]-[OH;D1;+0:10]>>[#7:7]-[C:6](=[O;D1;H0:8])-[C:5]1-[C:4]-[C:3]-1-[C;H0;D3;+0:1](=[O;D1;H0:2])-[O;H0;D2;+0:10]-[C;D1;H3:9]
null
[]
null
null
8
HOUR
A solution of 140 mg (0.36 mmol) of (1RS,2SR,3SR)-2-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenylcarbamoyl]-3-phenyl-cyclopropanecarboxylic acid in 5 ml of methanol was treated at 0° C. with ca. 0.1 ml of thionylchloride and left to stirr overnight at RT. Evaporation of the solvent gave 160 mg of (1RS,2SR,3SR)-2-[2-fluoro...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Methanol
Ester
null
null
C1CC1.c1ccccc1.c1ccncc1.c1ccccc1
HO-
null
null
8
CO.O=C(O)C1C(C(=O)Nc2ccc(-n3ccccc3=O)cc2F)C1c1ccccc1>>COC(=O)C1C(C(=O)Nc2ccc(-n3ccccc3=O)cc2F)C1c1ccccc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-94141face69b4a28a8869761c8e6b73a
CCOC(=O)C1C2COC(=O)C21.Nc1ccc(-n2ccccc2=O)cc1F>>CCOC(=O)C1C(CO)C1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
Cl.C(C)OC(=O)C1C2COC(C12)=O.NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F.C[Si](C)(C)[N-][Si](C)(C)C.[Li+]>>C(C)OC(=O)C1C(C1CO)C(NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F)=O
[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]1[CH:7]2[CH2:8][O:9][C:11](=[O:12])[CH:10]12.[NH2:13][c:14]1[cH:15][cH:16][c:17](-[n:18]2[cH:19][cH:20][cH:21][cH:22][c:23]2=[O:24])[cH:25][c:26]1[F:27]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]1[CH:7]([CH2:8][OH:9])[CH:10]1[C:11](=[O:12])[NH:13][c:14]1[cH:15][cH:16][c:17](-[n:18]2[c...
CCOC(=O)C1C2COC(=O)C21.Nc1ccc(-n2ccccc2=O)cc1F
CCOC(=O)C1C(CO)C1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
null
null
C1CCOC1
Acylation
OtherReaction
69a7881b740d2f5f830cdb942d0f936308bff4c2ddda3b485ae5d1afa3371fb1
93d3d2d91fa5d15fd0f361e38c72a0c2e4bde37efa822e4566162d5af70167b6
O=C(Nc1ccc(-n2ccccc2=O)cc1)C1CC1
[#8:1]-[C:2](=[O;D1;H0:3])-[C:4]1-[C:5]2-[C:6]-1-[C:7]-[O;H0;D2;+0:8]-[C;H0;D3;+0:9]-2=[O;D1;H0:10].[NH2;D1;+0:11]-[c:12](:[c:13]):[c:14]>>[#8:1]-[C:2](=[O;D1;H0:3])-[C:4]1-[C:5](-[C;H0;D3;+0:9](=[O;D1;H0:10])-[NH;D2;+0:11]-[c:12](:[c:13]):[c:14])-[C:6]-1-[C:7]-[OH;D1;+0:8]
58
[{"value": 57.0, "product": "C(C)OC(=O)C1C(C1CO)C(NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 58.0, "product": "C(C)OC(=O)C1C(C1CO)C(NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
30
MINUTE
A solution of 600 mg (2.9 mmol) of 1-(4-amino-3-fluoro-phenyl)-1H-pyridin-2-one (prepared according to C. F. Bigge et al., patent application WO 2003045912) in 10 ml of THF was cooled to −78° C. and treated dropwise with 3.2 ml of a 1M lithium bis(trimethylsilyl)amide-solution in THF and stirred for 30 min. To this sol...
10.6084/m9.figshare.5104873.v1
null
Ester.Primary amine
Secondary amide.Primary alcohol
C1OCC2CC12
null
C1CC1.c1ccccc1.c1ccncc1
null
C1CCOC1
null
0.5
CCOC(=O)C1C2COC(=O)C21.Nc1ccc(-n2ccccc2=O)cc1F>C1CCOC1>CCOC(=O)C1C(CO)C1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7dc9203d9e5b41e8b98b1e3760198f6b
COC(=O)C1C(C(=O)Nc2ccc(Cl)cn2)C1C(=O)Nc1ccc(-n2ccccc2=O)cc1F>>O=C(O)C1C(C(=O)Nc2ccc(Cl)cn2)C1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
Cl.COC(=O)C1C(C1C(NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F)=O)C(NC1=NC=C(C=C1)Cl)=O.[Li+].[OH-]>>ClC=1C=CC(=NC1)NC(=O)C1C(C1C(NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F)=O)C(=O)O
C[O:3][C:2](=[O:1])[CH:4]1[CH:5]([C:6](=[O:7])[NH:8][c:9]2[cH:10][cH:11][c:12]([Cl:13])[cH:14][n:15]2)[CH:16]1[C:17](=[O:18])[NH:19][c:20]1[cH:21][cH:22][c:23](-[n:24]2[cH:25][cH:26][cH:27][cH:28][c:29]2=[O:30])[cH:31][c:32]1[F:33]>>[O:1]=[C:2]([OH:3])[CH:4]1[CH:5]([C:6](=[O:7])[NH:8][c:9]2[cH:10][cH:11][c:12]([Cl:13])...
COC(=O)C1C(C(=O)Nc2ccc(Cl)cn2)C1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
O=C(O)C1C(C(=O)Nc2ccc(Cl)cn2)C1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
null
null
C1CCOC1
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
O=C(Nc1ccc(-n2ccccc2=O)cc1)C1CC1C(=O)Nc1ccccn1
C-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
68.3
[{"value": 68.0, "product": "ClC=1C=CC(=NC1)NC(=O)C1C(C1C(NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F)=O)C(=O)O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 68.3, "product": "ClC=1C=CC(=NC1)NC(=O)C1C(C1C(NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F)=O)C(=O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
A solution of 68 mg (0.14 mmol) of (1RS,2SR,3RS)-2-(5-chloro-pyridin-2-ylcarbamoyl)-3-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenylcarbamoyl]-cyclopropanecarboxylic acid methyl ester (example 114, step 5) in 1.5 ml of THF was treated with 0.2 ml of a 1M aqueous LiOH solution, stirred at RT during 2 hrs and acidified to pH...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
C1CC1.c1ccncc1.c1ccccc1.c1ccncc1
Other
C1CCOC1
null
2
COC(=O)C1C(C(=O)Nc2ccc(Cl)cn2)C1C(=O)Nc1ccc(-n2ccccc2=O)cc1F>C1CCOC1>O=C(O)C1C(C(=O)Nc2ccc(Cl)cn2)C1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-581c221020e9422f95f707d475439026
Nc1ccc(-n2ccc(OCc3ccccc3)cc2=O)cc1F>>Nc1ccc(-n2ccc(O)cc2=O)cc1F
NC1=C(C=C(C=C1)N1C(C=C(C=C1)OCC1=CC=CC=C1)=O)F>>NC1=C(C=C(C=C1)N1C(C=C(C=C1)O)=O)F
c1ccc(C[O:10][c:9]2[cH:8][cH:7][n:6](-[c:5]3[cH:4][cH:3][c:2]([NH2:1])[c:15]([F:16])[cH:14]3)[c:12](=[O:13])[cH:11]2)cc1>>[NH2:1][c:2]1[cH:3][cH:4][c:5](-[n:6]2[cH:7][cH:8][c:9]([OH:10])[cH:11][c:12]2=[O:13])[cH:14][c:15]1[F:16]
Nc1ccc(-n2ccc(OCc3ccccc3)cc2=O)cc1F
Nc1ccc(-n2ccc(O)cc2=O)cc1F
null
[Pd]
CO
Deprotection
Hydroxyl benzyl deprotection
36869d1fe85185a14d9eb30bf05178c600a9b6eca277ffaf3803578c30e0bf5d
26a36596df80ec137b0e8087297418351c93c32819177f680675220622f215d4
O=c1ccccn1-c1ccccc1
C(-[O;H0;D2;+0:1]-[c:2]1:[c:3]:[c:4]:[#7;a:5]:[c:6]:[c:7]:1)-c1:c:c:c:c:c:1>>[OH;D1;+0:1]-[c:2]1:[c:3]:[c:4]:[#7;a:5]:[c:6]:[c:7]:1
97
[{"value": 97.0, "product": "NC1=C(C=C(C=C1)N1C(C=C(C=C1)O)=O)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 96.7, "product": "NC1=C(C=C(C=C1)N1C(C=C(C=C1)O)=O)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
A solution of 580 mg (1.87 mmol) 1-(4-amino-3-fluoro-phenyl)-4-benzyloxy-1H-pyridin-2-one (example 144, step 1) in 20 ml of MeOH was treated with 140 mg of Pd/C (10%) and hydrogenated at atmospheric pressure under vigorous stirring for 3 hrs. Filtration and evaporation of the solvent gave 398 mg (97%) of 1-(4-Amino-3-f...
10.6084/m9.figshare.5104873.v1
null
Ether
Aromatic alcohol
c1ccccc1
null
c1ccccc1.c1ccncc1
Other
[Pd].CO
null
3
Nc1ccc(-n2ccc(OCc3ccccc3)cc2=O)cc1F>[Pd].CO>Nc1ccc(-n2ccc(O)cc2=O)cc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-71f674dad4e143ab951272dcf324cfbc
CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccc(O)cc2=O)cc1F.COS(=O)(=O)OC>>CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccc(OC)cc2=O)cc1F
C(C)OC(=O)C1C(C1C(NC1=C(C=C(C=C1)N1C(C=C(C=C1)O)=O)F)=O)C(NC1=CC=C(C=C1)Cl)=O.C([O-])([O-])=O.[K+].[K+].COS(=O)(=O)OC>>C(C)OC(=O)C1C(C1C(NC1=C(C=C(C=C1)N1C(C=C(C=C1)OC)=O)F)=O)C(NC1=CC=C(C=C1)Cl)=O
[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]1[CH:7]([C:8](=[O:9])[NH:10][c:11]2[cH:12][cH:13][c:14]([Cl:15])[cH:16][cH:17]2)[CH:18]1[C:19](=[O:20])[NH:21][c:22]1[cH:23][cH:24][c:25](-[n:26]2[cH:27][cH:28][c:29]([OH:30])[cH:32][c:33]2=[O:34])[cH:35][c:36]1[F:37].COS(=O)(=O)O[CH3:31]>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[CH:6]1[CH...
CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccc(O)cc2=O)cc1F.COS(=O)(=O)OC
CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccc(OC)cc2=O)cc1F
null
null
CC(=O)C
Heteroatom Alkylation and Arylation
Methylation of OH with DMS
b8b041187bac58376aae824630608e7deb49a01db3d652291f8b379c10d4e434
0f0966e3597a58033417ecee71659f4d0c082f95d46b1e52c95541e6e4a59086
O=C(Nc1ccccc1)C1CC1C(=O)Nc1ccc(-n2ccccc2=O)cc1
C-O-S(=O)(=O)-O-[CH3;D1;+0:1].[OH;D1;+0:2]-[c:3]1:[c:4]:[c:5]:[#7;a:6]:[c:7]:[c:8]:1>>[CH3;D1;+0:1]-[O;H0;D2;+0:2]-[c:3]1:[c:4]:[c:5]:[#7;a:6]:[c:7]:[c:8]:1
13.5
[{"value": 13.0, "product": "C(C)OC(=O)C1C(C1C(NC1=C(C=C(C=C1)N1C(C=C(C=C1)OC)=O)F)=O)C(NC1=CC=C(C=C1)Cl)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 13.5, "product": "C(C)OC(=O)C1C(C1C(NC1=C(C=C(C=C1)N1C(C=C(C=C1)OC)=O)F)=O)C(NC1=CC=C(C=C1)Cl)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": f...
null
null
2
HOUR
A solution of 35 mg (0.07 mmol) of (1SR,2RS,3SR)-2-(4-chloro-phenylcarbamoyl)-3-[2-fluoro-4-(4-hydroxy-2-oxo-2H-pyridin-1-yl)-phenylcarbamoyl]-cyclopropanecarboxylic acid ethyl ester (example 142, step 2) in 5 ml of acetone was treated with 94 mg (0.6 mmol) of potassium carbonate and 8 ul (0.08 mmol) of dimethylsulfate...
10.6084/m9.figshare.5104873.v1
null
Aromatic alcohol
Ether
null
null
C1CC1.c1ccccc1.c1ccccc1.c1ccncc1
HO-
CC(=O)C
null
2
CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccc(O)cc2=O)cc1F.COS(=O)(=O)OC>CC(=O)C>CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccc(OC)cc2=O)cc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-34c53b7818264de3813ba31788b88df6
Nc1ccc(Br)cc1F.O=c1cc(OCc2ccccc2)cc[nH]1>>Nc1ccc(-n2ccc(OCc3ccccc3)cc2=O)cc1F
C(C1=CC=CC=C1)OC1=CC(NC=C1)=O.BrC1=CC(=C(N)C=C1)F.NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F>>NC1=C(C=C(C=C1)N1C(C=C(C=C1)OCC1=CC=CC=C1)=O)F
Br[c:5]1[cH:4][cH:3][c:2]([NH2:1])[c:22]([F:23])[cH:21]1.[nH:6]1[cH:7][cH:8][c:9]([O:10][CH2:11][c:12]2[cH:13][cH:14][cH:15][cH:16][cH:17]2)[cH:18][c:19]1=[O:20]>>[NH2:1][c:2]1[cH:3][cH:4][c:5](-[n:6]2[cH:7][cH:8][c:9]([O:10][CH2:11][c:12]3[cH:13][cH:14][cH:15][cH:16][cH:17]3)[cH:18][c:19]2=[O:20])[cH:21][c:22]1[F:23]
Nc1ccc(Br)cc1F.O=c1cc(OCc2ccccc2)cc[nH]1
Nc1ccc(-n2ccc(OCc3ccccc3)cc2=O)cc1F
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
c4bca3c6c7e7a85c1215b056751d6c9e665b6c9ad3e374f5595f04141f3d67ff
e3660767655c50df0f92afc78c794dd2af7cf646bf1430960eafd30c23bf3fa7
O=c1cc(OCc2ccccc2)ccn1-c1ccccc1
Br-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[O;D1;H0:6]=[c:7](:[c:8]):[nH;D2;+0:9]:[c:10]:[c:11]>>[O;D1;H0:6]=[c:7](:[c:8]):[n;H0;D3;+0:9](-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5]):[c:10]:[c:11]
null
[]
null
null
null
null
1-(4-Amino-3-fluoro-phenyl)-4-benzyloxy-1H-pyridin-2-one was prepared from 4-benzyloxy-1H-pyridin-2-one and 4-bromo-2-fluoroaniline in analogy to the procedure described for the preparation of 1-(4-amino-3-fluoro-phenyl)-1H-pyridin-2-one described in C. F. Bigge et al., patent application WO 2003045912. MS: 311 (M+H)+....
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
null
c1ccccc1.c1ccncc1
c1ccccc1.c1ccncc1
c1ccccc1.c1ccncc1.c1ccccc1
HBr
null
null
null
Nc1ccc(Br)cc1F.O=c1cc(OCc2ccccc2)cc[nH]1>>Nc1ccc(-n2ccc(OCc3ccccc3)cc2=O)cc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4b6f7ef19e5547d19076744adbf0728d
CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccc(OCC(=O)O)cc2=O)cc1F.CNC>>CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccc(OCC(=O)N(C)C)cc2=O)cc1F
Cl.C(C)OC(=O)C1C(C1C(NC1=CC=C(C=C1)Cl)=O)C(NC1=C(C=C(C=C1)N1C(C=C(C=C1)OCC(=O)O)=O)F)=O.Cl.CNC.ON1N=NC2=C1C=CC=C2.CN1CCOCC1.Cl.CN(CCCN=C=NCC)C>>C(C)OC(=O)C1C(C1C(NC1=C(C=C(C=C1)N1C(C=C(C=C1)OCC(N(C)C)=O)=O)F)=O)C(NC1=CC=C(C=C1)Cl)=O
O[C:32]([CH2:31][O:30][c:29]1[cH:28][cH:27][n:26](-[c:25]2[cH:24][cH:23][c:22]([NH:21][C:19]([CH:18]3[CH:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[CH:7]3[C:8](=[O:9])[NH:10][c:11]3[cH:12][cH:13][c:14]([Cl:15])[cH:16][cH:17]3)=[O:20])[c:41]([F:42])[cH:40]2)[c:38](=[O:39])[cH:37]1)=[O:33].[NH:34]([CH3:35])[CH3:36]>>[CH3:1][CH...
CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccc(OCC(=O)O)cc2=O)cc1F.CNC
CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccc(OCC(=O)N(C)C)cc2=O)cc1F
null
null
CN(C)C=O
Acylation
Acylation of Nitrogen Nucleophiles by Carboxylic Acids
ac72df6259d5d7baee7abdbd4706ef4b4627f86ead9dc94f0cefcfcb37c21def
c5e4172490b2731ba9322b68af56376edadc31ce0bb9a3dfdea23a1817a852fd
O=C(Nc1ccccc1)C1CC1C(=O)Nc1ccc(-n2ccccc2=O)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[#8:4].[C;D1;H3:5]-[NH;D2;+0:6]-[C;D1;H3:7]>>[#8:4]-[C:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[N;H0;D3;+0:6](-[C;D1;H3:5])-[C;D1;H3:7]
95
[{"value": 95.0, "product": "C(C)OC(=O)C1C(C1C(NC1=C(C=C(C=C1)N1C(C=C(C=C1)OCC(N(C)C)=O)=O)F)=O)C(NC1=CC=C(C=C1)Cl)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 91.8, "product": "C(C)OC(=O)C1C(C1C(NC1=C(C=C(C=C1)N1C(C=C(C=C1)OCC(N(C)C)=O)=O)F)=O)C(NC1=CC=C(C=C1)Cl)=O", "details": "CALCULATEDPERCENTYIE...
null
null
10
HOUR
A mixture of 23 mg (0.04 mmol) of (1SR,2RS,3SR) 2-[4-(4-carboxymethoxy-2-oxo-2H-pyridin-1-yl)-2-fluoro-phenylcarbamoyl]-3-(4-chloro-phenylcarbamoyl) cyclopropanecarboxylic acid ethyl ester (example 155), 5 mg (0.06 mmol) of dimethylamine hydrochloride, 1 mg of 1-hydroxybenzotriazole, and 25 ul (0.23 mmol) of N-methylmo...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Tertiary amide
null
null
C1CC1.c1ccccc1.c1ccccc1.c1ccncc1
HO-
CN(C)C=O
null
10
CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccc(OCC(=O)O)cc2=O)cc1F.CNC>CN(C)C=O>CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccc(OCC(=O)N(C)C)cc2=O)cc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f88b300ee6cc4b8eab49e12e227ee7d7
CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccc(OCC(=O)OC(C)(C)C)cc2=O)cc1F>>CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccc(OCC(=O)O)cc2=O)cc1F
C(C)OC(=O)C1C(C1C(NC1=CC=C(C=C1)Cl)=O)C(NC1=C(C=C(C=C1)N1C(C=C(C=C1)OCC(=O)OC(C)(C)C)=O)F)=O.FC(C(=O)O)(F)F>>C(C)OC(=O)C1C(C1C(NC1=CC=C(C=C1)Cl)=O)C(NC1=C(C=C(C=C1)N1C(C=C(C=C1)OCC(=O)O)=O)F)=O
CC(C)(C)[O:34][C:32]([CH2:31][O:30][c:29]1[cH:28][cH:27][n:26](-[c:25]2[cH:24][cH:23][c:22]([NH:21][C:19]([CH:18]3[CH:6]([C:4]([O:3][CH2:2][CH3:1])=[O:5])[CH:7]3[C:8](=[O:9])[NH:10][c:11]3[cH:12][cH:13][c:14]([Cl:15])[cH:16][cH:17]3)=[O:20])[c:39]([F:40])[cH:38]2)[c:36](=[O:37])[cH:35]1)=[O:33]>>[CH3:1][CH2:2][O:3][C:4...
CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccc(OCC(=O)OC(C)(C)C)cc2=O)cc1F
CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccc(OCC(=O)O)cc2=O)cc1F
null
null
null
Deprotection
Deprotection of carboxylic acid
152e5537e48c95b4a3e767536b0f9f68d1308e5f484070828ab5ed951805157a
7f019d4cfe9b3036d0a2d3a3209aa0e1fcb05418ebee15a4be5e125d315d5f01
O=C(Nc1ccccc1)C1CC1C(=O)Nc1ccc(-n2ccccc2=O)cc1
C-C(-C)(-C)-[O;H0;D2;+0:1]-[C:2](-[C:3])=[O;D1;H0:4]>>[C:3]-[C:2](=[O;D1;H0:4])-[OH;D1;+0:1]
69
[{"value": 69.0, "product": "C(C)OC(=O)C1C(C1C(NC1=CC=C(C=C1)Cl)=O)C(NC1=C(C=C(C=C1)N1C(C=C(C=C1)OCC(=O)O)=O)F)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 67.8, "product": "C(C)OC(=O)C1C(C1C(NC1=CC=C(C=C1)Cl)=O)C(NC1=C(C=C(C=C1)N1C(C=C(C=C1)OCC(=O)O)=O)F)=O", "details": "CALCULATEDPERCENTYIELD", "is...
75
CELSIUS
40
MINUTE
A solution of 49 mg (0.08 mmol) of (1SR,2SR,3RS)-2-[4-(4-tert-butoxycarbonylmethoxy-2-oxo-2H-pyridin-1-yl)-2-fluoro-phenylcarbamoyl]-3-(4-chloro-phenylcarbamoyl)-cyclopropanecarboxylic acid ethyl ester in 3 ml of 1,2-dichloromethane was treated with 28 ul of trifluoroacetic acid and stirred at 75° C. during 40 min. Eva...
10.6084/m9.figshare.5104873.v1
null
Ester.Boc
Carboxylic acid
null
null
C1CC1.c1ccccc1.c1ccccc1.c1ccncc1
Other
null
75
0.666667
CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccc(OCC(=O)OC(C)(C)C)cc2=O)cc1F>>CCOC(=O)C1C(C(=O)Nc2ccc(Cl)cc2)C1C(=O)Nc1ccc(-n2ccc(OCC(=O)O)cc2=O)cc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-228c5fc2707a43a489978db56dbc3af7
COc1ccc(CCl)cc1.OC/C=C/CO>>COc1ccc(COC/C=C/CO)cc1
[Na+].[Cl-].COC1=CC=C(CCl)C=C1.C(\C=C\CO)O.[H-].[Na+]>>COC1=CC=C(COC/C=C/CO)C=C1
Cl[CH2:7][c:6]1[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:15][cH:14]1.[OH:8][CH2:9]/[CH:10]=[CH:11]/[CH2:12][OH:13]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][O:8][CH2:9]/[CH:10]=[CH:11]/[CH2:12][OH:13])[cH:14][cH:15]1
COc1ccc(CCl)cc1.OC/C=C/CO
COc1ccc(COC/C=C/CO)cc1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
dd3f9c60e1f90d961a7c01d970ae213561355ee1451f276a3b04696e4b6fae5c
46a6e883cf919b4006e69abfdfd883f458f55c08b3200960c6a5b57c4139fbca
c1ccccc1
Cl-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4].[C:5]/[C:6]=[C:7]/[C:8]-[OH;D1;+0:9]>>[C:5]/[C:6]=[C:7]/[C:8]-[O;H0;D2;+0:9]-[CH2;D2;+0:1]-[c:2](:[c:3]):[c:4]
21
[{"value": 21.0, "product": "COC1=CC=C(COC/C=C/CO)C=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 20.5, "product": "COC1=CC=C(COC/C=C/CO)C=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
45
MINUTE
A solution of 11.8 g (133.4 mmol) of trans 2-butene-1,4-diol in 100 ml of DMF was treated with 6.4 g (147 mmol) of sodium hydride dispersion on oil (55%), stirred at 0° C. for 45 min., and treated dropwise with 25.1 g (160 mmol) of 4-methoxybenzylchloride. The mixture was stirred during 5 hrs at RT and then poured into...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Primary alcohol
Ether
null
null
c1ccccc1
HCl
CN(C)C=O
0
0.75
COc1ccc(CCl)cc1.OC/C=C/CO>CN(C)C=O>COc1ccc(COC/C=C/CO)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-15f35c06e96d498e9afbd4d1d1db75ea
COc1ccc(COCC=CCOC(=O)C=[N+]=[N-])cc1>>COc1ccc(COC[C@H]2[C@@H]3COC(=O)[C@H]23)cc1
COC1=CC=C(COCC=CCOC(C=[N+]=[N-])=O)C=C1>>COC1=CC=C(COC[C@H]2[C@@H]3COC([C@H]23)=O)C=C1
[N-]=[N+]=[CH:16][C:14]([O:13][CH2:12][CH:11]=[CH:10][CH2:9][O:8][CH2:7][c:6]1[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:18][cH:17]1)=[O:15]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][O:8][CH2:9][C@H:10]2[C@@H:11]3[CH2:12][O:13][C:14](=[O:15])[C@H:16]23)[cH:17][cH:18]1
COc1ccc(COCC=CCOC(=O)C=[N+]=[N-])cc1
COc1ccc(COC[C@H]2[C@@H]3COC(=O)[C@H]23)cc1
null
null
ClCCl
C-C Coupling
OtherReaction
48aae0167faec840c55360f4c42a9634a99b490782f71ffc3d251e8d2acde28f
2bf044f9aa3102f7e58ada063c1d8beb18b3b23505b944ca768ff7e6f4f49661
O=C1OC[C@H]2[C@H](COCc3ccccc3)[C@@H]12
[#8:1]-[C:2]-[CH;D2;+0:3]=[CH;D2;+0:4]-[C:5]-[#8:6]-[C:7](=[O;D1;H0:8])-[CH;D2;+0:9]=[N+]=[N-]>>[#8:1]-[C:2]-[C@H;D3;+0:3]1-[C@@H;D3;+0:4]2-[C:5]-[#8:6]-[C:7](=[O;D1;H0:8])-[C@@H;D3;+0:9]-2-1
96
[{"value": 96.0, "product": "COC1=CC=C(COC[C@H]2[C@@H]3COC([C@H]23)=O)C=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 95.1, "product": "COC1=CC=C(COC[C@H]2[C@@H]3COC([C@H]23)=O)C=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a solution of 1 g (3.6 mmol) of diazo-acetic acid 4-(4-methoxy-benzyloxy)-but-2-enyl ester in 50 ml dichloromethane under reflux were added within 8 hrs of 25 mg (0.03 mmol) of Rh2 (5S-MEPY)4 (Doyle dirhodium catalyst from Acros, CAS: 132435-65-5) dissolved in 100 ml of dichloromethane. Refluxing for another 20 hrs,...
10.6084/m9.figshare.5104873.v1
null
Ester.Diazo
Ester
null
C1OC[C@H]2C[C@@H]12
c1ccccc1.C1OC[C@H]2C[C@@H]12
Other
ClCCl
null
null
COc1ccc(COCC=CCOC(=O)C=[N+]=[N-])cc1>ClCCl>COc1ccc(COC[C@H]2[C@@H]3COC(=O)[C@H]23)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-82455f92875a431cb285d19e454c5c5e
COc1ccc(COC[C@H]2[C@@H]3COC(=O)[C@H]23)cc1.Nc1ccc(-n2ccccc2=O)cc1F>>COc1ccc(COC[C@H]2[C@H](CO)[C@@H]2C(=O)Nc2ccc(-n3ccccc3=O)cc2F)cc1
C[Si](C)(C)[N-][Si](C)(C)C.[Li+].Cl.NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F.COC1=CC=C(COC[C@H]2[C@@H]3COC([C@H]23)=O)C=C1>>FC1=C(C=CC(=C1)N1C(C=CC=C1)=O)NC(=O)[C@H]1[C@H]([C@@H]1COCC1=CC=C(C=C1)OC)CO
[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][O:8][CH2:9][C@H:10]2[C@@H:11]3[CH2:12][O:13][C:15](=[O:16])[C@H:14]23)[cH:32][cH:33]1.[NH2:17][c:18]1[cH:19][cH:20][c:21](-[n:22]2[cH:23][cH:24][cH:25][cH:26][c:27]2=[O:28])[cH:29][c:30]1[F:31]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][O:8][CH2:9][C@H:10]2[C@H:11]([CH2:12]...
COc1ccc(COC[C@H]2[C@@H]3COC(=O)[C@H]23)cc1.Nc1ccc(-n2ccccc2=O)cc1F
COc1ccc(COC[C@H]2[C@H](CO)[C@@H]2C(=O)Nc2ccc(-n3ccccc3=O)cc2F)cc1
null
null
CCOC(=O)C.C1CCOC1
Acylation
OtherReaction
d131db01cc7882f6b2dc1d75ead3a8190f440b4eb2c2ab2d5243808c1dcc3dd5
93d3d2d91fa5d15fd0f361e38c72a0c2e4bde37efa822e4566162d5af70167b6
O=C(Nc1ccc(-n2ccccc2=O)cc1)[C@H]1C[C@@H]1COCc1ccccc1
[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4].[O;D1;H0:5]=[C;H0;D3;+0:6]1-[O;H0;D2;+0:7]-[C:8]-[C:9]2-[C:10]-[C:11]-2-1>>[O;D1;H0:5]=[C;H0;D3;+0:6](-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4])-[C:11]1-[C:10]-[C:9]-1-[C:8]-[OH;D1;+0:7]
78
[{"value": 77.0, "product": "FC1=C(C=CC(=C1)N1C(C=CC=C1)=O)NC(=O)[C@H]1[C@H]([C@@H]1COCC1=CC=C(C=C1)OC)CO", "details": "PERCENTYIELD", "is_desired": false}, {"value": 78.0, "product": "FC1=C(C=CC(=C1)N1C(C=CC=C1)=O)NC(=O)[C@H]1[C@H]([C@@H]1COCC1=CC=C(C=C1)OC)CO", "details": "CALCULATEDPERCENTYIELD", "is_desired": false...
78
CELSIUS
30
MINUTE
A solution of 850 mg (3.4 mmol) of 1-(4-amino-3-fluoro-phenyl)-1H-pyridin-2-one (prepared according to C. F. Bigge et al., patent application WO 2003045912) in 80 ml of THF was cooled to −78° C., treated dropwise with 4.8 ml of a 1M lithium bis(trimethylsilyl)amide-solution in THF and stirred for 30 min at 78° C. To th...
10.6084/m9.figshare.5104873.v1
null
Ester.Primary amine
Secondary amide.Primary alcohol
C1OC[C@H]2C[C@@H]12
null
c1ccccc1.C1CC1.c1ccccc1.c1ccncc1
null
CCOC(=O)C.C1CCOC1
78
0.5
COc1ccc(COC[C@H]2[C@@H]3COC(=O)[C@H]23)cc1.Nc1ccc(-n2ccccc2=O)cc1F>CCOC(=O)C.C1CCOC1>COc1ccc(COC[C@H]2[C@H](CO)[C@@H]2C(=O)Nc2ccc(-n3ccccc3=O)cc2F)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b684634275db4f42b800778664501e6f
CI.COc1ccc(OC[C@@H]2[C@@H](C(=O)Nc3ccc(-n4ccccc4=O)cc3F)[C@H]2C(=O)O)cc1>>COC(=O)[C@H]1[C@H](COc2ccc(OC)cc2)[C@H]1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
[OH-].[Na+].FC1=C(C=CC(=C1)N1C(C=CC=C1)=O)NC(=O)[C@H]1[C@H]([C@@H]1COC1=CC=C(C=C1)OC)C(=O)O.C(=O)([O-])[O-].[K+].[K+].IC>>COC(=O)[C@@H]1[C@@H]([C@H]1COC1=CC=C(C=C1)OC)C(NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F)=O
I[CH3:1].[OH:2][C:3](=[O:4])[C@H:5]1[C@H:6]([CH2:7][O:8][c:9]2[cH:10][cH:11][c:12]([O:13][CH3:14])[cH:15][cH:16]2)[C@H:17]1[C:18](=[O:19])[NH:20][c:21]1[cH:22][cH:23][c:24](-[n:25]2[cH:26][cH:27][cH:28][cH:29][c:30]2=[O:31])[cH:32][c:33]1[F:34]>>[CH3:1][O:2][C:3](=[O:4])[C@H:5]1[C@H:6]([CH2:7][O:8][c:9]2[cH:10][cH:11][...
CI.COc1ccc(OC[C@@H]2[C@@H](C(=O)Nc3ccc(-n4ccccc4=O)cc3F)[C@H]2C(=O)O)cc1
COC(=O)[C@H]1[C@H](COc2ccc(OC)cc2)[C@H]1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
9474aa79a2adc7353c0c02444ca598a6f486ecdd7ed5edb9ae0645721ee50389
badd4f82161bb0ee7acffd023ea4caae5d036bce7065c10ab0a06e83a6a6f119
O=C(Nc1ccc(-n2ccccc2=O)cc1)[C@H]1C[C@@H]1COc1ccccc1
I-[CH3;D1;+0:1].[C:2]-[C:3](=[O;D1;H0:4])-[OH;D1;+0:5]>>[C:2]-[C:3](=[O;D1;H0:4])-[O;H0;D2;+0:5]-[CH3;D1;+0:1]
101.5
[{"value": 97.0, "product": "COC(=O)[C@@H]1[C@@H]([C@H]1COC1=CC=C(C=C1)OC)C(NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 101.5, "product": "COC(=O)[C@@H]1[C@@H]([C@H]1COC1=CC=C(C=C1)OC)C(NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F)=O", "details": "CALCULATEDPERCENTYIELD", "is_desi...
null
null
3
HOUR
A solution of 90 mg (0.19 mmol) of (1S,2R,3R) 2-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenylcarbamoyl]-3-(4-methoxy-phenoxymethyl)-cyclopropanecarboxylic acid in 3 ml of DMF was treated with 100 mg of K2CO3 and 0.5 ml ml of iodomethane. The mixture was stirred for 3 hrs and poured into a diluted aqueous solution of NaOH....
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid
Ester
null
null
C1CC1.c1ccccc1.c1ccccc1.c1ccncc1
HI
CN(C)C=O
null
3
CI.COc1ccc(OC[C@@H]2[C@@H](C(=O)Nc3ccc(-n4ccccc4=O)cc3F)[C@H]2C(=O)O)cc1>CN(C)C=O>COC(=O)[C@H]1[C@H](COc2ccc(OC)cc2)[C@H]1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-23b3204104d74d3296d53d262f0c8187
CC1(C(=O)O)CC1C(=O)Nc1ccc(Cl)cn1.CO>>COC(=O)C1(C)CC1C(=O)Nc1ccc(Cl)cn1
ClC=1C=CC(=NC1)NC(=O)C1C(C1)(C(=O)O)C.CO>>COC(=O)C1(C(C1)C(NC1=NC=C(C=C1)Cl)=O)C
O[C:3](=[O:4])[C:5]1([CH3:6])[CH2:7][CH:8]1[C:9](=[O:10])[NH:11][c:12]1[cH:13][cH:14][c:15]([Cl:16])[cH:17][n:18]1.[CH3:1][OH:2]>>[CH3:1][O:2][C:3](=[O:4])[C:5]1([CH3:6])[CH2:7][CH:8]1[C:9](=[O:10])[NH:11][c:12]1[cH:13][cH:14][c:15]([Cl:16])[cH:17][n:18]1
CC1(C(=O)O)CC1C(=O)Nc1ccc(Cl)cn1.CO
COC(=O)C1(C)CC1C(=O)Nc1ccc(Cl)cn1
null
S(=O)(Cl)Cl.S(=O)(Cl)Cl
null
Protection
Esterification of Carboxylic Acids
9cecdbd189c6f9c3648521d17154d013842a5498de4e76e65efb1d842973340b
af0b8064f2e82ebe66c4c29d2391785ac1b993104265ccdc4d67ca79e36fa3c8
O=C(Nc1ccccn1)C1CC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]1(-[C;D1;H3:4])-[C:5]-[C:6]-1-[C:7](-[#7:8])=[O;D1;H0:9].[C;D1;H3:10]-[OH;D1;+0:11]>>[#7:8]-[C:7](=[O;D1;H0:9])-[C:6]1-[C:5]-[C:3]-1(-[C;D1;H3:4])-[C;H0;D3;+0:1](=[O;D1;H0:2])-[O;H0;D2;+0:11]-[C;D1;H3:10]
null
[]
0
CELSIUS
null
null
A suspension of (1SR,2RS)-2-(5-chloro-pyridin-2-ylcarbamoyl)-1-methyl-cyclopropane-carboxylic acid (176 mg) in MeOH (5 ml) was cooled to 0° C. and treated with thionyl chloride (15 drops). After stirring for 2 hrs at 0° C. additional thionyl chloride (10 drops) was added. The clear solution was concentrated. The crude ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Methanol
Ester
null
null
C1CC1.c1ccncc1
HO-
S(=O)(Cl)Cl.S(=O)(Cl)Cl
0
null
CC1(C(=O)O)CC1C(=O)Nc1ccc(Cl)cn1.CO>S(=O)(Cl)Cl.S(=O)(Cl)Cl>COC(=O)C1(C)CC1C(=O)Nc1ccc(Cl)cn1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4503bf05abfa4d1e8d80f322c67cb6b6
Nc1ccc(-n2ccccc2=O)cc1F.O=C1OC(=O)C2CC12>>O=C(O)C1CC1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
C12C(OC(C2C1)=O)=O.NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F>>FC1=C(C=CC(=C1)N1C(C=CC=C1)=O)NC(=O)C1C(C1)C(=O)O
[NH2:9][c:10]1[cH:11][cH:12][c:13](-[n:14]2[cH:15][cH:16][cH:17][cH:18][c:19]2=[O:20])[cH:21][c:22]1[F:23].[O:1]=[C:2]1[O:3][C:7](=[O:8])[CH:6]2[CH:4]1[CH2:5]2>>[O:1]=[C:2]([OH:3])[CH:4]1[CH2:5][CH:6]1[C:7](=[O:8])[NH:9][c:10]1[cH:11][cH:12][c:13](-[n:14]2[cH:15][cH:16][cH:17][cH:18][c:19]2=[O:20])[cH:21][c:22]1[F:23]
Nc1ccc(-n2ccccc2=O)cc1F.O=C1OC(=O)C2CC12
O=C(O)C1CC1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
null
null
C1CCOC1
Acylation
OtherReaction
e703520c7562ce45f4229de31c7594eb37a30a19130a8d74d6df634b89de6365
babc03c287bd8cfa2865fae168af372e93ed67f910f700d8b87af94362c61841
O=C(Nc1ccc(-n2ccccc2=O)cc1)C1CC1
[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4].[O;D1;H0:5]=[C:6]1-[O;H0;D2;+0:7]-[C;H0;D3;+0:8](=[O;D1;H0:9])-[C:10]2-[C:11]-[C:12]-1-2>>[O;D1;H0:5]=[C:6](-[OH;D1;+0:7])-[C:12]1-[C:11]-[C:10]-1-[C;H0;D3;+0:8](=[O;D1;H0:9])-[NH;D2;+0:1]-[c:2](:[c:3]):[c:4]
31.9
[{"value": 31.9, "product": "FC1=C(C=CC(=C1)N1C(C=CC=C1)=O)NC(=O)C1C(C1)C(=O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A solution of 3-oxabicyclo[3.1.0]hexane-2,4-dione (160 mg) in THF (5 ml) was treated with 1-(4-amino-3-fluoro-phenyl)-1H-pyridin-2-one (321 mg; CAS 536747-52-1, prepared according to C. F. Bigge et al., patent application WO 2003045912). The suspension was stirred over night at r.t. The solid was collected by filtratio...
10.6084/m9.figshare.5104873.v1
null
Anhydride.Primary amine
Carboxylic acid.Secondary amide
C1OCC2CC12
null
C1CC1.c1ccccc1.c1ccncc1
null
C1CCOC1
null
null
Nc1ccc(-n2ccccc2=O)cc1F.O=C1OC(=O)C2CC12>C1CCOC1>O=C(O)C1CC1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d491ba9104c64357b1bf083aa7de18f9
CO.O=C(O)C1CC1C(=O)Nc1ccc(-n2ccccc2=O)cc1F>>COC(=O)C1CC1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
FC1=C(C=CC(=C1)N1C(C=CC=C1)=O)NC(=O)C1C(C1)C(=O)O.CO>>COC(=O)C1C(C1)C(NC1=C(C=C(C=C1)N1C(C=CC=C1)=O)F)=O
[CH3:1][OH:2].O[C:3](=[O:4])[CH:5]1[CH2:6][CH:7]1[C:8](=[O:9])[NH:10][c:11]1[cH:12][cH:13][c:14](-[n:15]2[cH:16][cH:17][cH:18][cH:19][c:20]2=[O:21])[cH:22][c:23]1[F:24]>>[CH3:1][O:2][C:3](=[O:4])[CH:5]1[CH2:6][CH:7]1[C:8](=[O:9])[NH:10][c:11]1[cH:12][cH:13][c:14](-[n:15]2[cH:16][cH:17][cH:18][cH:19][c:20]2=[O:21])[cH:2...
CO.O=C(O)C1CC1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
COC(=O)C1CC1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
null
S(=O)(Cl)Cl
null
Protection
Esterification of Carboxylic Acids
9cecdbd189c6f9c3648521d17154d013842a5498de4e76e65efb1d842973340b
af0b8064f2e82ebe66c4c29d2391785ac1b993104265ccdc4d67ca79e36fa3c8
O=C(Nc1ccc(-n2ccccc2=O)cc1)C1CC1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]1-[C:4]-[C:5]-1-[C:6](-[#7:7])=[O;D1;H0:8].[C;D1;H3:9]-[OH;D1;+0:10]>>[#7:7]-[C:6](=[O;D1;H0:8])-[C:5]1-[C:4]-[C:3]-1-[C;H0;D3;+0:1](=[O;D1;H0:2])-[O;H0;D2;+0:10]-[C;D1;H3:9]
null
[]
0
CELSIUS
3
HOUR
A stirred suspension of (1RS,2SR)-2-[2-fluoro-4-(2-oxo-2H-pyridin-1-yl)-phenylcarbamoyl]-cyclopropanecarboxylic acid (140 mg) in MeOH (5 ml) was cooled to 0° C. and treated with thionyl chloride (10 drops). The mixture turned immediately into a clear solution. Stirring was continued for 3 hrs at 0° C. Then the reaction...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Methanol
Ester
null
null
C1CC1.c1ccccc1.c1ccncc1
HO-
S(=O)(Cl)Cl
0
3
CO.O=C(O)C1CC1C(=O)Nc1ccc(-n2ccccc2=O)cc1F>S(=O)(Cl)Cl>COC(=O)C1CC1C(=O)Nc1ccc(-n2ccccc2=O)cc1F
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9d805015ed7f431bbc8d0c72fbb7b28f
COc1cccc(CCN)c1.N#C[O-]>>COc1cccc(CCNC(N)=O)c1
COC=1C=C(C=CC1)CCN.Cl.[O-]C#N.[K+]>>COC=1C=C(C=CC1)CCNC(=O)N
[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][c:7]([CH2:8][CH2:9][NH2:10])[cH:14]1.[C:11](#[N:12])[O-:13]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][c:7]([CH2:8][CH2:9][NH:10][C:11]([NH2:12])=[O:13])[cH:14]1
COc1cccc(CCN)c1.N#C[O-]
COc1cccc(CCNC(N)=O)c1
null
null
O
Acylation
OtherReaction
f8798d1193af6f9b314ac8855e814716b90ff3758bcfa29778cc632fcaa83b7a
5efe06db19c806d9e9798893351dc14c0cc48f1e8f8c857f54c6171e86c96a1b
c1ccccc1
[C:1]-[C:2]-[NH2;D1;+0:3].[N;H0;D1;+0:4]#[C;H0;D2;+0:5]-[O-;H0;D1:6]>>[C:1]-[C:2]-[NH;D2;+0:3]-[C;H0;D3;+0:5](-[NH2;D1;+0:4])=[O;H0;D1;+0:6]
83.1
[{"value": 83.0, "product": "COC=1C=C(C=CC1)CCNC(=O)N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 83.1, "product": "COC=1C=C(C=CC1)CCNC(=O)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
50
CELSIUS
2
HOUR
To a solution of 2-(3-methoxy-phenyl)-ethylamine (1) (50.0 g, 331 mmol) and concentrated HCl (27.6 mL) in water (350 mL), potassium cyanate (28.2 g, 348 mmol) was added and stirred at 50° C. for 2 hours, then at room temperature for 2 days. Formed precipitate was collected by filtration. The solid was washed with water...
10.6084/m9.figshare.5104873.v1
null
Nitrile.Primary amine
Urea
null
null
c1ccccc1
null
O
50
2
COc1cccc(CCN)c1.N#C[O-]>O>COc1cccc(CCNC(N)=O)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9f43836919cc44168d960ef77667b36f
CCO.COc1cccc(CCNC(N)=O)c1.COc1cccc(CCNC(N)=O)c1>>COc1cccc(CCN2C(=O)CC(=O)NC2=O)c1
O.COC=1C=C(C=CC1)CCNC(=O)N.CCO.CC[O-].[Na+].CCO.COC=1C=C(C=CC1)CCNC(=O)N.CCO.Cl>>COC=1C=C(C=CC1)CCN1C(NC(CC1=O)=O)=O
[CH3:13][CH2:14][OH:15].COc1cccc(CCN[C:17]([NH2:16])=[O:18])c1.N[C:11]([NH:10][CH2:9][CH2:8][c:7]1[cH:6][cH:5][cH:4][c:3]([O:2][CH3:1])[cH:19]1)=[O:12]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][c:7]([CH2:8][CH2:9][N:10]2[C:11](=[O:12])[CH2:13][C:14](=[O:15])[NH:16][C:17]2=[O:18])[cH:19]1
CCO.COc1cccc(CCNC(N)=O)c1.COc1cccc(CCNC(N)=O)c1
COc1cccc(CCN2C(=O)CC(=O)NC2=O)c1
null
null
null
C-C Coupling
OtherReaction
b7ca0daf00e44af477d8b8b8c083fc5050fa3b397a12547a6331f3ff762b2a22
e7ff2d155be7a3b7decc6e2151672c81c36269e075e29092e633dcf1e6958c07
O=C1CC(=O)N(CCc2ccccc2)C(=O)N1
C-O-c1:c:c:c:c(-C-C-N-[C;H0;D3;+0:1](-[NH2;D1;+0:2])=[O;D1;H0:3]):c:1.N-[C;H0;D3;+0:4](=[O;D1;H0:5])-[NH;D2;+0:6]-[C:7]-[C:8].[CH3;D1;+0:9]-[CH2;D2;+0:10]-[OH;D1;+0:11]>>[C:8]-[C:7]-[N;H0;D3;+0:6]1-[C;H0;D3;+0:4](=[O;D1;H0:5])-[CH2;D2;+0:9]-[C;H0;D3;+0:10](=[O;H0;D1;+0:11])-[NH;D2;+0:2]-[C;H0;D3;+0:1]-1=[O;D1;H0:3]
74
[{"value": 74.0, "product": "COC=1C=C(C=CC1)CCN1C(NC(CC1=O)=O)=O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
To a solution of NaOEt (144 mmol, fleshly prepared from 3.3 g of Na) in EtOH (80 mL), a solution of ethyl malonate (2) (22 mL, 144 mmol) in EtOH (250 mL) was added. The mixture was refluxed then added a solution of [2-(3-methoxy-phenyl)-ethyl]-urea (2) (23.3 g, 120 mmol) in EtOH (300 mL). The reaction mixture was reflu...
10.6084/m9.figshare.5104873.v1
null
Ether.Urea.Urea.Primary alcohol
Urea.Unsubstituted dicarboximide.Substituted dicarboximide
c1ccccc1
C1C[NH]CNC1
c1ccccc1.C1C[NH]CNC1
HO-
null
null
null
CCO.COc1cccc(CCNC(N)=O)c1.COc1cccc(CCNC(N)=O)c1>>COc1cccc(CCN2C(=O)CC(=O)NC2=O)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-28670c17abff4d0d958f5c309490c30d
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1ccc2[nH]ncc2c1>>COc1ccc2c(c1)CCn1c-2cc(Nc2ccc3[nH]ncc3c2)nc1=O
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.N1N=CC2=CC(=CC=C12)N>>N1N=CC2=CC(=CC=C12)NC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O
Cl[c:14]1[cH:13][c:12]2[n:11]([c:26](=[O:27])[n:25]1)[CH2:10][CH2:9][c:7]1[c:6]-2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:8]1.[NH2:15][c:16]1[cH:17][cH:18][c:19]2[nH:20][n:21][cH:22][c:23]2[cH:24]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][c:16]2[cH:17][cH:18][c:19...
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1ccc2[nH]ncc2c1
COc1ccc2c(c1)CCn1c-2cc(Nc2ccc3[nH]ncc3c2)nc1=O
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
c8475104970a63fce3d52b085fd15febf776cee9f570c7a80516c8bef4cb52de
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=c1nc(Nc2ccc3[nH]ncc3c2)cc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[C:9]-[#7;a:5]1:[c:6](:[c:7]:[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[#7;a:2]:[c:3]:1=[O;D1;H0:4])-[c:8]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and 1H-indazol-5-ylamine as in Example 1 d. 1H-NMR (400 MHz, d6-DMSO) δ 13.00 (br, 1H), 9.60 (s, 1H), 8.36 (br, 1H), 8.06 (s, 1H), 7.69 (d, 1H), 7.51 (m, 2H), 7.10-6.95 (2H), 6.35 (s, 1H), 3.99 (t, 2H), 3.84 (s, 3H)...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21.c1ccc2[nH]ncc2c1
HCl
null
null
null
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1ccc2[nH]ncc2c1>>COc1ccc2c(c1)CCn1c-2cc(Nc2ccc3[nH]ncc3c2)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f48d66c02cb24b2da3b05215ca1ea5b0
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.COc1cccc(C)c1N>>COc1ccc2c(c1)CCn1c-2cc(Nc2c(C)cccc2OC)nc1=O
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.COC1=C(N)C(=CC=C1)C>>COC=1C=C2CCN3C(C2=CC1)=CC(=NC3=O)NC3=C(C=CC=C3C)OC
Cl[c:14]1[cH:13][c:12]2[n:11]([c:26](=[O:27])[n:25]1)[CH2:10][CH2:9][c:7]1[c:6]-2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:8]1.[NH2:15][c:16]1[c:17]([CH3:18])[cH:19][cH:20][cH:21][c:22]1[O:23][CH3:24]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][c:16]2[c:17]([CH3:18])[...
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.COc1cccc(C)c1N
COc1ccc2c(c1)CCn1c-2cc(Nc2c(C)cccc2OC)nc1=O
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
c8475104970a63fce3d52b085fd15febf776cee9f570c7a80516c8bef4cb52de
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=c1nc(Nc2ccccc2)cc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[C:9]-[#7;a:5]1:[c:6](:[c:7]:[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[#7;a:2]:[c:3]:1=[O;D1;H0:4])-[c:8]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and 2-methoxy-6-methyl-aniline as in Example 1 d. 1H-NMR (400 MHz, d6-DMSO) δ 8.71 (br, 1H), 7.71 (br, 1H), 7.35-6.80 (5H), 6.39 (br, 1H), 3.92 (br, 2H), 3.83 (br, 3H), 3.74 (br, 3H), 2.94 (t, 2H) and 2.14 (br, 3H);...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21.c1ccccc1
HCl
null
null
null
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.COc1cccc(C)c1N>>COc1ccc2c(c1)CCn1c-2cc(Nc2c(C)cccc2OC)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2634d225563c4a6a92ea2b62881e43a7
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1ccc2cn[nH]c2c1>>COc1ccc2c(c1)CCn1c-2cc(Nc2ccc3cn[nH]c3c2)nc1=O
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.N1N=CC2=CC=C(C=C12)N>>N1N=CC2=CC=C(C=C12)NC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O
Cl[c:14]1[cH:13][c:12]2[n:11]([c:26](=[O:27])[n:25]1)[CH2:10][CH2:9][c:7]1[c:6]-2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:8]1.[NH2:15][c:16]1[cH:17][cH:18][c:19]2[cH:20][n:21][nH:22][c:23]2[cH:24]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][c:16]2[cH:17][cH:18][c:19...
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1ccc2cn[nH]c2c1
COc1ccc2c(c1)CCn1c-2cc(Nc2ccc3cn[nH]c3c2)nc1=O
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
c8475104970a63fce3d52b085fd15febf776cee9f570c7a80516c8bef4cb52de
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=c1nc(Nc2ccc3cn[nH]c3c2)cc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[#7;a:10]:[c:11]:[c:12]:[c:13](-[NH2;D1;+0:14]):[c:15]>>[#7;a:10]:[c:11]:[c:12]:[c:13](-[NH;D2;+0:14]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9]):[c:15]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and 1H-indazol-6-ylamine as in Example 1 d. 1H-NMR (400 MHz, d6-DMSO) δ 12.95 (br, 1H), 9.76 (s, 1H), 8.60 (s, 1H), 7.96 (s, 1H), 7.72-7.60 (2H), 7.15-6.95 (3H), 6.42 (s, 1H), 4.01 (t, 2H), 3.85 (s, 3H) and 2.98 (t,...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21.c1ccc2n[nH]cc2c1
HCl
null
null
null
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1ccc2cn[nH]c2c1>>COc1ccc2c(c1)CCn1c-2cc(Nc2ccc3cn[nH]c3c2)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-692a05dc5eb14e8ca643b1e2a0b9b9dc
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1ccccc1Br>>COc1ccc2c(c1)CCn1c-2cc(Nc2ccccc2Br)nc1=O
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.BrC1=C(N)C=CC=C1>>BrC1=C(C=CC=C1)NC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O
Cl[c:14]1[cH:13][c:12]2[n:11]([c:24](=[O:25])[n:23]1)[CH2:10][CH2:9][c:7]1[c:6]-2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:8]1.[NH2:15][c:16]1[cH:17][cH:18][cH:19][cH:20][c:21]1[Br:22]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][c:16]2[cH:17][cH:18][cH:19][cH:20][c:21...
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1ccccc1Br
COc1ccc2c(c1)CCn1c-2cc(Nc2ccccc2Br)nc1=O
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
c8475104970a63fce3d52b085fd15febf776cee9f570c7a80516c8bef4cb52de
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=c1nc(Nc2ccccc2)cc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[C:9]-[#7;a:5]1:[c:6](:[c:7]:[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[#7;a:2]:[c:3]:1=[O;D1;H0:4])-[c:8]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and 2-bromo-aniline as in Example 1 d. 1H-NMR (400 MHz, d6-DMSO) δ 9.06 (br, 1H), 7.76 (br, 1H), 7.69 (2H), 7.41 (t, 1H), 7.16 (t, 1H), 7.05-6.95 (2H), 6.47 (br, 1H), 3.96 (t, 2H), 3.84 (s, 3H) and 2.96 (t, 2H); MS ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21.c1ccccc1
HCl
null
null
null
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1ccccc1Br>>COc1ccc2c(c1)CCn1c-2cc(Nc2ccccc2Br)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3476ab91ea64458395b40ed72ba1626d
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1cccc(S(N)(=O)=O)c1>>COc1ccc2c(c1)CCn1c-2cc(Nc2cccc(S(N)(=O)=O)c2)nc1=O
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.NC=1C=C(C=CC1)S(=O)(=O)N>>COC=1C=C2CCN3C(C2=CC1)=CC(=NC3=O)NC=3C=C(C=CC3)S(=O)(=O)N
Cl[c:14]1[cH:13][c:12]2[n:11]([c:27](=[O:28])[n:26]1)[CH2:10][CH2:9][c:7]1[c:6]-2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:8]1.[NH2:15][c:16]1[cH:17][cH:18][cH:19][c:20]([S:21]([NH2:22])(=[O:23])=[O:24])[cH:25]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][c:16]2[cH:17...
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1cccc(S(N)(=O)=O)c1
COc1ccc2c(c1)CCn1c-2cc(Nc2cccc(S(N)(=O)=O)c2)nc1=O
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
c8475104970a63fce3d52b085fd15febf776cee9f570c7a80516c8bef4cb52de
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=c1nc(Nc2ccccc2)cc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[C:9]-[#7;a:5]1:[c:6](:[c:7]:[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[#7;a:2]:[c:3]:1=[O;D1;H0:4])-[c:8]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and 3-amino-benzenesulfonamide as in Example 1 d. 1H-NMR (400 MHz, d6-DMSO) δ 9.91 (s, 1H), 8.17 (d, 1H), 8.11 (s, 1H), 7.70 (d, 1H), 7.54 (t, 1H), 7.48 (d, 1H), 7.39 (br, 2H), 7.05-6.98 (2H), 6.37 (s, 1H), 4.00 (t,...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21.c1ccccc1
HCl
null
null
null
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1cccc(S(N)(=O)=O)c1>>COc1ccc2c(c1)CCn1c-2cc(Nc2cccc(S(N)(=O)=O)c2)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ae42f06ab2d6487b929a0031b4ccdb27
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1ccccc1Cl>>COc1ccc2c(c1)CCn1c-2cc(Nc2ccccc2Cl)nc1=O
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.ClC1=C(N)C=CC=C1>>ClC1=C(C=CC=C1)NC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O
Cl[c:14]1[cH:13][c:12]2[n:11]([c:24](=[O:25])[n:23]1)[CH2:10][CH2:9][c:7]1[c:6]-2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:8]1.[NH2:15][c:16]1[cH:17][cH:18][cH:19][cH:20][c:21]1[Cl:22]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][c:16]2[cH:17][cH:18][cH:19][cH:20][c:21...
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1ccccc1Cl
COc1ccc2c(c1)CCn1c-2cc(Nc2ccccc2Cl)nc1=O
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
c8475104970a63fce3d52b085fd15febf776cee9f570c7a80516c8bef4cb52de
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=c1nc(Nc2ccccc2)cc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[C:9]-[#7;a:5]1:[c:6](:[c:7]:[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[#7;a:2]:[c:3]:1=[O;D1;H0:4])-[c:8]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and 2-chloro-aniline as in Example 1 d. 1H-NMR (400 MHz, d6-DMSO) δ 9.10 (br, 1H), 7.91 (brd, 1H), 7.70 (brd, 1H), 7.53 (dd, 1H), 7.37 (t, 1H), 7.21 (t, 1H), 7.05-6.95 (2H), 6.55 (br, 1H), 3.97 (t, 2H), 3.84 (s, 3H)...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21.c1ccccc1
HCl
null
null
null
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1ccccc1Cl>>COc1ccc2c(c1)CCn1c-2cc(Nc2ccccc2Cl)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-da40987323084fe2ad68f524ed25d5a7
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Cc1cccc(C)c1N>>COc1ccc2c(c1)CCn1c-2cc(Nc2c(C)cccc2C)nc1=O
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.CC1=C(N)C(=CC=C1)C>>CC1=C(C(=CC=C1)C)NC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O
Cl[c:14]1[cH:13][c:12]2[n:11]([c:25](=[O:26])[n:24]1)[CH2:10][CH2:9][c:7]1[c:6]-2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:8]1.[NH2:15][c:16]1[c:17]([CH3:18])[cH:19][cH:20][cH:21][c:22]1[CH3:23]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][c:16]2[c:17]([CH3:18])[cH:19]...
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Cc1cccc(C)c1N
COc1ccc2c(c1)CCn1c-2cc(Nc2c(C)cccc2C)nc1=O
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
c8475104970a63fce3d52b085fd15febf776cee9f570c7a80516c8bef4cb52de
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=c1nc(Nc2ccccc2)cc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[C:9]-[#7;a:5]1:[c:6](:[c:7]:[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[#7;a:2]:[c:3]:1=[O;D1;H0:4])-[c:8]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and 2,6-dimethyl-aniline as in Example 1 d. 1H-NMR as two isomeric mixture (400 MHz, d6-DMSO) δ 8.96 and 8.87 (br, 1H), 7.75 and 7.29 (d, 1H), 7.23-6.80 (5H), 6.37 and 5.33 (br, 1H), 3.96 and 3.92 (t, 2H), 3.84 and ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21.c1ccccc1
HCl
null
null
null
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Cc1cccc(C)c1N>>COc1ccc2c(c1)CCn1c-2cc(Nc2c(C)cccc2C)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-b3272511036a47d788066056645698f7
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1c(F)cccc1Br>>COc1ccc2c(c1)CCn1c-2cc(Nc2c(F)cccc2Br)nc1=O
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.BrC1=C(N)C(=CC=C1)F>>BrC1=C(C(=CC=C1)F)NC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O
Cl[c:14]1[cH:13][c:12]2[n:11]([c:25](=[O:26])[n:24]1)[CH2:10][CH2:9][c:7]1[c:6]-2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:8]1.[NH2:15][c:16]1[c:17]([F:18])[cH:19][cH:20][cH:21][c:22]1[Br:23]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][c:16]2[c:17]([F:18])[cH:19][cH:2...
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1c(F)cccc1Br
COc1ccc2c(c1)CCn1c-2cc(Nc2c(F)cccc2Br)nc1=O
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
c8475104970a63fce3d52b085fd15febf776cee9f570c7a80516c8bef4cb52de
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=c1nc(Nc2ccccc2)cc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[C:9]-[#7;a:5]1:[c:6](:[c:7]:[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[#7;a:2]:[c:3]:1=[O;D1;H0:4])-[c:8]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and 2-bromo-6-fluoro-aniline as in Example 1 d. 1H-NMR (400 MHz, d6-DMSO) δ 9.26 (br, 1H), 7.72 (br, 1H), 7.57 (brd, 1H), 7.34 (br, 2H), 7.05-6.95 (2H), 6.37 (br, 1H), 3.94 (t, 2H), 3.84 (s, 3H) and 2.96 (t, 2H); MS...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21.c1ccccc1
HCl
null
null
null
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1c(F)cccc1Br>>COc1ccc2c(c1)CCn1c-2cc(Nc2c(F)cccc2Br)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-fc0adbbcac84454fbc08c21418c2b918
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.COc1cccc(N)c1>>COc1cccc(Nc2cc3n(c(=O)n2)CCc2cc(OC)ccc2-3)c1
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.COC=1C=C(N)C=CC1>>COC=1C=C(C=CC1)NC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O
Cl[c:9]1[cH:10][c:11]2[n:12]([c:13](=[O:14])[n:15]1)[CH2:16][CH2:17][c:18]1[cH:19][c:20]([O:21][CH3:22])[cH:23][cH:24][c:25]1-2.[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][c:7]([NH2:8])[cH:26]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][c:7]([NH:8][c:9]2[cH:10][c:11]3[n:12]([c:13](=[O:14])[n:15]2)[CH2:16][CH2:17][c:18]2[cH:19][c:2...
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.COc1cccc(N)c1
COc1cccc(Nc2cc3n(c(=O)n2)CCc2cc(OC)ccc2-3)c1
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
c8475104970a63fce3d52b085fd15febf776cee9f570c7a80516c8bef4cb52de
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=c1nc(Nc2ccccc2)cc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[C:9]-[#7;a:5]1:[c:6](:[c:7]:[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[#7;a:2]:[c:3]:1=[O;D1;H0:4])-[c:8]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and 3-methoxyaniline as in Example 1 d. 1H-NMR (400 MHz, d6-DMSO) δ 9.59 (s, 1H), 7.68 (d, 1H), 7.52 (br, 1H), 7.30 (d, 1H), 7.23 (t, 1H), 7.05-6.95 (2H), 6.63 (dd, 1H), 6.35 (s, 1H), 3.98 (t, 2H), 3.84 (s, 3H), 3.7...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccccc1.c1ccc2c(c1)CCn1cnccc21
HCl
null
null
null
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.COc1cccc(N)c1>>COc1cccc(Nc2cc3n(c(=O)n2)CCc2cc(OC)ccc2-3)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1213ad2a0e2b4298960163ed0da23b17
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Cc1cccc(O)c1N>>COc1ccc2c(c1)CCn1c-2cc(Nc2c(C)cccc2O)nc1=O
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.OC1=C(N)C(=CC=C1)C>>OC1=C(C(=CC=C1)C)NC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O
Cl[c:14]1[cH:13][c:12]2[n:11]([c:25](=[O:26])[n:24]1)[CH2:10][CH2:9][c:7]1[c:6]-2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:8]1.[NH2:15][c:16]1[c:17]([CH3:18])[cH:19][cH:20][cH:21][c:22]1[OH:23]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][c:16]2[c:17]([CH3:18])[cH:19][...
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Cc1cccc(O)c1N
COc1ccc2c(c1)CCn1c-2cc(Nc2c(C)cccc2O)nc1=O
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
c8475104970a63fce3d52b085fd15febf776cee9f570c7a80516c8bef4cb52de
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=c1nc(Nc2ccccc2)cc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[C:9]-[#7;a:5]1:[c:6](:[c:7]:[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[#7;a:2]:[c:3]:1=[O;D1;H0:4])-[c:8]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and 2-hydroxy-6-methyl-aniline as in Example 1 d. 1H-NMR (400 MHz, d6-DMSO, at 60° C.) δ 9.39 (br, 1H), 8.60 (br, 1H), 7.61 (br, 1H), 7.05-6.95 (3H), 6.75 (d, 1H), 6.73 (d, 1H), 6.34 (br, 1H), 3.95 (t, 2H), 3.83 (s,...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21.c1ccccc1
HCl
null
null
null
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Cc1cccc(O)c1N>>COc1ccc2c(c1)CCn1c-2cc(Nc2c(C)cccc2O)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-bf986b7aaf984030a8ed8da032def2d9
COc1ccc(-c2ccccc2)cc1N.COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O>>COc1ccc2c(c1)CCn1c-2cc(Nc2cc(-c3ccccc3)ccc2OC)nc1=O
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.NC=1C=C(C=CC1OC)C1=CC=CC=C1>>COC=1C=C2CCN3C(C2=CC1)=CC(=NC3=O)NC=3C=C(C=CC3OC)C3=CC=CC=C3
[NH2:15][c:16]1[cH:17][c:18](-[c:19]2[cH:20][cH:21][cH:22][cH:23][cH:24]2)[cH:25][cH:26][c:27]1[O:28][CH3:29].Cl[c:14]1[cH:13][c:12]2[n:11]([c:31](=[O:32])[n:30]1)[CH2:10][CH2:9][c:7]1[c:6]-2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:8]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c...
COc1ccc(-c2ccccc2)cc1N.COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O
COc1ccc2c(c1)CCn1c-2cc(Nc2cc(-c3ccccc3)ccc2OC)nc1=O
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
c8475104970a63fce3d52b085fd15febf776cee9f570c7a80516c8bef4cb52de
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=c1nc(Nc2cccc(-c3ccccc3)c2)cc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[C:9]-[#7;a:5]1:[c:6](:[c:7]:[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[#7;a:2]:[c:3]:1=[O;D1;H0:4])-[c:8]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and 3-amino-4-methoxy-biphenyl as in Example 1 d. 1H-NMR (400 MHz, d8-DMSO) δ 8.85 (s, 1H), 8.55 (br, 1H), 7.70 (d, 1H), 7.60 (d, 2H), 7.46 (t, 2H), 7.38 (dd, 1H), 7.33 (t, 1H), 7.16 (d, 1H), 7.02 (dd, 1H), 6.98 (d,...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21.c1ccccc1.c1ccccc1
HCl
null
null
null
COc1ccc(-c2ccccc2)cc1N.COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O>>COc1ccc2c(c1)CCn1c-2cc(Nc2cc(-c3ccccc3)ccc2OC)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d9f835ed430e4e08ae863940294eabf6
CCOC(=O)c1cccc(N)c1.COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O>>CCOC(=O)c1cccc(Nc2cc3n(c(=O)n2)CCc2cc(OC)ccc2-3)c1
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.C(C)OC(C1=CC(=CC=C1)N)=O>>C(C)OC(C1=CC(=CC=C1)NC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O)=O
[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][cH:8][cH:9][c:10]([NH2:11])[cH:29]1.Cl[c:12]1[cH:13][c:14]2[n:15]([c:16](=[O:17])[n:18]1)[CH2:19][CH2:20][c:21]1[cH:22][c:23]([O:24][CH3:25])[cH:26][cH:27][c:28]1-2>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[cH:7][cH:8][cH:9][c:10]([NH:11][c:12]2[cH:13][c:14]3[n:15]([c:16](=[O:...
CCOC(=O)c1cccc(N)c1.COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O
CCOC(=O)c1cccc(Nc2cc3n(c(=O)n2)CCc2cc(OC)ccc2-3)c1
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
c8475104970a63fce3d52b085fd15febf776cee9f570c7a80516c8bef4cb52de
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=c1nc(Nc2ccccc2)cc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[C:9]-[#7;a:5]1:[c:6](:[c:7]:[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[#7;a:2]:[c:3]:1=[O;D1;H0:4])-[c:8]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and 3-amino-benzoic acid ethyl ester as in Example 1 d. 1H-NMR (400 MHz, d0-DMSO) δ 9.84 (s, 1H), 8.26 (s, 1H), 8.21 (d, 1H), 7.70 (d, 1H), 7.62 (d, 1H), 7.49 (t, 1H), 7.05-6.97 (2H), 6.36 (s, 1H), 4.33 (q, 2H), 3.9...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccccc1.c1ccc2c(c1)CCn1cnccc21
HCl
null
null
null
CCOC(=O)c1cccc(N)c1.COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O>>CCOC(=O)c1cccc(Nc2cc3n(c(=O)n2)CCc2cc(OC)ccc2-3)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e9e6ae9ae5d84a0db20bb294f7ccb050
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.COc1ccccc1N>>COc1ccc2c(c1)CCn1c-2cc(Nc2ccccc2OC)nc1=O
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.COC1=C(N)C=CC=C1>>COC=1C=C2CCN3C(C2=CC1)=CC(=NC3=O)NC3=C(C=CC=C3)OC
Cl[c:14]1[cH:13][c:12]2[n:11]([c:25](=[O:26])[n:24]1)[CH2:10][CH2:9][c:7]1[c:6]-2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:8]1.[NH2:15][c:16]1[cH:17][cH:18][cH:19][cH:20][c:21]1[O:22][CH3:23]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][c:16]2[cH:17][cH:18][cH:19][cH:2...
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.COc1ccccc1N
COc1ccc2c(c1)CCn1c-2cc(Nc2ccccc2OC)nc1=O
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
c8475104970a63fce3d52b085fd15febf776cee9f570c7a80516c8bef4cb52de
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=c1nc(Nc2ccccc2)cc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[C:9]-[#7;a:5]1:[c:6](:[c:7]:[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[#7;a:2]:[c:3]:1=[O;D1;H0:4])-[c:8]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and 2-methoxy-aniline as in Example 1 d. 1H-NMR (400 MHz, d6-DMSO) 88.74 (s, 1H), 8.24 (br, 1H), 7.69 (d, 1H), 7.12-6.92 (5H), 6.70 (br, 1H), 3.97 (t, 2H), 3.87 (s, 3H), 3.84 (s, 3H) and 2.96 (t, 2H); MS (ESI) (M+H)...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21.c1ccccc1
HCl
null
null
null
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.COc1ccccc1N>>COc1ccc2c(c1)CCn1c-2cc(Nc2ccccc2OC)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-5841729151dc4f0c9c7ee07f39357ea2
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1ccccc1C(F)(F)F>>COc1ccc2c(c1)CCn1c-2cc(Nc2ccccc2C(F)(F)F)nc1=O
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.FC(C1=C(N)C=CC=C1)(F)F>>COC=1C=C2CCN3C(C2=CC1)=CC(=NC3=O)NC3=C(C=CC=C3)C(F)(F)F
Cl[c:14]1[cH:13][c:12]2[n:11]([c:27](=[O:28])[n:26]1)[CH2:10][CH2:9][c:7]1[c:6]-2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:8]1.[NH2:15][c:16]1[cH:17][cH:18][cH:19][cH:20][c:21]1[C:22]([F:23])([F:24])[F:25]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][c:16]2[cH:17][cH:1...
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1ccccc1C(F)(F)F
COc1ccc2c(c1)CCn1c-2cc(Nc2ccccc2C(F)(F)F)nc1=O
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
c8475104970a63fce3d52b085fd15febf776cee9f570c7a80516c8bef4cb52de
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=c1nc(Nc2ccccc2)cc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[C:9]-[#7;a:5]1:[c:6](:[c:7]:[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[#7;a:2]:[c:3]:1=[O;D1;H0:4])-[c:8]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and 2-trifluoromethyl-aniline as in Example 1 d. 1H-NMR (400 MHz, d6-DMSO) δ 9.10 (br, 1H), 7.90-7.35 (5H), 6.98 (2H), 6.42 (br, 1H), 3.94 (brt, 2H), 3.83 (s, 3H) and 2.95 (t, 2H); MS (ESI) (M+H)+ 388. Conditions: S...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21.c1ccccc1
HCl
null
null
null
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1ccccc1C(F)(F)F>>COc1ccc2c(c1)CCn1c-2cc(Nc2ccccc2C(F)(F)F)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-eff3521913c2417e908e24d825848e7c
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Cc1cc(Cl)cc(C)c1N>>COc1ccc2c(c1)CCn1c-2cc(Nc2c(C)cc(Cl)cc2C)nc1=O
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.ClC1=CC(=C(N)C(=C1)C)C>>ClC1=CC(=C(C(=C1)C)NC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O)C
Cl[c:14]1[cH:13][c:12]2[n:11]([c:26](=[O:27])[n:25]1)[CH2:10][CH2:9][c:7]1[c:6]-2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:8]1.[NH2:15][c:16]1[c:17]([CH3:18])[cH:19][c:20]([Cl:21])[cH:22][c:23]1[CH3:24]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][c:16]2[c:17]([CH3:18]...
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Cc1cc(Cl)cc(C)c1N
COc1ccc2c(c1)CCn1c-2cc(Nc2c(C)cc(Cl)cc2C)nc1=O
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
c8475104970a63fce3d52b085fd15febf776cee9f570c7a80516c8bef4cb52de
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=c1nc(Nc2ccccc2)cc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[C:9]-[#7;a:5]1:[c:6](:[c:7]:[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[#7;a:2]:[c:3]:1=[O;D1;H0:4])-[c:8]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and 4-Chloro-2,6-dimethyl-aniline as in Example 1 d. 1H-NMR (400 MHz, d6-DMSO) δ 8.73 (br, 1H), 7.72 (br, 1H), 7.19 (s, 2H), 7.03-6.95 (2H), 6.36 (br, 1H), 3.95 (t, 2H), 3.85 (s, 3H), 2.96 (t, 2H) and 2.18 (s, 6H); ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21.c1ccccc1
HCl
null
null
null
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Cc1cc(Cl)cc(C)c1N>>COc1ccc2c(c1)CCn1c-2cc(Nc2c(C)cc(Cl)cc2C)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ffc01c1b489b4d53a6148a0d3a600342
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1cccc2ncccc12>>COc1ccc2c(c1)CCn1c-2cc(Nc2cccc3ncccc23)nc1=O
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.NC1=C2C=CC=NC2=CC=C1>>COC=1C=C2CCN3C(C2=CC1)=CC(=NC3=O)NC3=C1C=CC=NC1=CC=C3
Cl[c:14]1[cH:13][c:12]2[n:11]([c:27](=[O:28])[n:26]1)[CH2:10][CH2:9][c:7]1[c:6]-2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:8]1.[NH2:15][c:16]1[cH:17][cH:18][cH:19][c:20]2[n:21][cH:22][cH:23][cH:24][c:25]12>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][c:16]2[cH:17][cH:1...
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1cccc2ncccc12
COc1ccc2c(c1)CCn1c-2cc(Nc2cccc3ncccc23)nc1=O
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
c8475104970a63fce3d52b085fd15febf776cee9f570c7a80516c8bef4cb52de
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=c1nc(Nc2cccc3ncccc23)cc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[#7;a:10]:[c:11]:[c:12]:[c:13](-[NH2;D1;+0:14]):[c:15]>>[#7;a:10]:[c:11]:[c:12]:[c:13](-[NH;D2;+0:14]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9]):[c:15]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and 5-amino-quinoline as in Example 1 d. 1H-NMR (400 MHz, d6-DMSO) δ 9.68 (br, 1H), 8.93 (dd, 1H), 8.47 (d, 1H), 7.89 (2H), 7.79 (t, 1H), 7.70 (d, 1H), 7.57 (dd, 1H), 7.03-6.97 (2H), 6.49 (br, 1H), 3.97 (t, 2H), 3.8...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21.c1ccc2ncccc2c1
HCl
null
null
null
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1cccc2ncccc12>>COc1ccc2c(c1)CCn1c-2cc(Nc2cccc3ncccc23)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-c16444c92ddc4fdfa9dee910b7189801
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.NNc1ccccc1Br>>COc1ccc2c(c1)CCn1c-2cc(NNc2ccccc2Br)nc1=O
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.BrC1=C(C=CC=C1)NN>>BrC1=C(C=CC=C1)NNC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O
Cl[c:14]1[cH:13][c:12]2[n:11]([c:25](=[O:26])[n:24]1)[CH2:10][CH2:9][c:7]1[c:6]-2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:8]1.[NH2:15][NH:16][c:17]1[cH:18][cH:19][cH:20][cH:21][c:22]1[Br:23]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][NH:16][c:17]2[cH:18][cH:19][cH:2...
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.NNc1ccccc1Br
COc1ccc2c(c1)CCn1c-2cc(NNc2ccccc2Br)nc1=O
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
ce26decf59eb6bfa42e6c1e2b26f98592223e1c8c92a1a68b7456a5e295b547b
61806bbf8bb8981e140ee503663af0ef0e69dc4f34f6582f974a2e4218f7da88
O=c1nc(NNc2ccccc2)cc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[NH2;D1;+0:10]-[#7:11]-[c:12]>>[C:9]-[#7;a:5]1:[c:6](:[c:7]:[c;H0;D3;+0:1](-[NH;D2;+0:10]-[#7:11]-[c:12]):[#7;a:2]:[c:3]:1=[O;D1;H0:4])-[c:8]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and (2-bromo-phenyl)-hydrazine as in Example 1 d. 1H-NMR (400 MHz, d6-DMSO at 60° C.) δ 9.19 (br, 1H), 7.66 (brd, 1H), 7.46 (d, 1H), 7.44 (br, 1H), 7.20 (t, 1H), 6.98-6.75 (3H), 6.71 (t, 1H), 6.23 (s, 1H), 3.94 (t, ...
10.6084/m9.figshare.5104873.v1
null
Hydrazine.Aromatic halide
Hydrazine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21.c1ccccc1
HCl
null
null
null
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.NNc1ccccc1Br>>COc1ccc2c(c1)CCn1c-2cc(NNc2ccccc2Br)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ba53c7a73ab848acbfbb41d961be87ed
CN(N)c1ccccc1.COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O>>COc1ccc2c(c1)CCn1c-2cc(NN(C)c2ccccc2)nc1=O
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.CN(N)C1=CC=CC=C1>>COC=1C=C2CCN3C(C2=CC1)=CC(=NC3=O)NN(C3=CC=CC=C3)C
[NH2:15][N:16]([CH3:17])[c:18]1[cH:19][cH:20][cH:21][cH:22][cH:23]1.Cl[c:14]1[cH:13][c:12]2[n:11]([c:25](=[O:26])[n:24]1)[CH2:10][CH2:9][c:7]1[c:6]-2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:8]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][N:16]([CH3:17])[c:18]2[cH:19]...
CN(N)c1ccccc1.COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O
COc1ccc2c(c1)CCn1c-2cc(NN(C)c2ccccc2)nc1=O
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
ce26decf59eb6bfa42e6c1e2b26f98592223e1c8c92a1a68b7456a5e295b547b
61806bbf8bb8981e140ee503663af0ef0e69dc4f34f6582f974a2e4218f7da88
O=c1nc(NNc2ccccc2)cc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[C;D1;H3:10]-[#7:11](-[NH2;D1;+0:12])-[c:13]>>[C:9]-[#7;a:5]1:[c:6](:[c:7]:[c;H0;D3;+0:1](-[NH;D2;+0:12]-[#7:11](-[C;D1;H3:10])-[c:13]):[#7;a:2]:[c:3]:1=[O;D1;H0:4])-[c:8]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and N-methyl-N-phenyl-hydrazine as in Example 1 d. 1H-NMR (400 MHz, d6-DMSO at 60° C.) δ 9.12 (br, 1H), 7.68 (d, 1H), 7.22 (t, 2H), 6.95-6.75 (5H), 6.24 (s, 1H), 3.96 (br, 2H), 3.82 (s, 3H), 3.16 (s, 3H) and 2.94 (t...
10.6084/m9.figshare.5104873.v1
null
Hydrazine.Aromatic halide
Hydrazine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21.c1ccccc1
HCl
null
null
null
CN(N)c1ccccc1.COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O>>COc1ccc2c(c1)CCn1c-2cc(NN(C)c2ccccc2)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-6580181d4669429b928a3ea281be0832
CC(C)(C)OC(=O)NCCN.COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O>>COc1ccc2c(c1)CCn1c-2cc(NCCN)nc1=O
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.C(=O)(OC(C)(C)C)NCCN.Cl>>NCCNC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O
CC(C)(C)OC(=O)[NH:18][CH2:17][CH2:16][NH2:15].Cl[c:14]1[cH:13][c:12]2[n:11]([c:20](=[O:21])[n:19]1)[CH2:10][CH2:9][c:7]1[c:6]-2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:8]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][CH2:16][CH2:17][NH2:18])[n:19][c:20]1=[O:21]
CC(C)(C)OC(=O)NCCN.COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O
COc1ccc2c(c1)CCn1c-2cc(NCCN)nc1=O
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
382dfd19e134b9fc7475f308567af6de9b45919acfda7adb00989c5ee9ce7027
b189e21881719932ff7e93d2cee73d5d9b679e27f974877dd5fa270130c3c7ff
O=c1nccc2n1CCc1ccccc1-2
C-C(-C)(-C)-O-C(=O)-[NH;D2;+0:1]-[C:2]-[C:3]-[NH2;D1;+0:4].Cl-[c;H0;D3;+0:5]1:[#7;a:6]:[c:7](=[O;D1;H0:8]):[#7;a:9](:[c:10](:[c:11]:1)-[c:12])-[C:13]>>[C:13]-[#7;a:9]1:[c:10](:[c:11]:[c;H0;D3;+0:5](-[NH;D2;+0:4]-[C:3]-[C:2]-[NH2;D1;+0:1]):[#7;a:6]:[c:7]:1=[O;D1;H0:8])-[c:12]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and N-Boc-ethylenediamine as in Example 1 d, followed by treatment with HCl. 1H-NMR as mixture of two isomers (400 MHz, d6-DMSO) δ 9.25-8.40 (1H), 8.32 and 7.70 (d, 1H), 8.12 and 8.02 (br, 3H), 7.07-7.00 (m, 2H), 6....
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Carbamic ester.Ether.Primary amine.Boc
Primary amine.Secondary amine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
HCl
null
null
null
CC(C)(C)OC(=O)NCCN.COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O>>COc1ccc2c(c1)CCn1c-2cc(NCCN)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-1e5338f5ebdd4ad69327ba6377e40e8b
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.NCCN1CCCC1>>COc1ccc2c(c1)CCn1c-2cc(NCCN2CCCC2)nc1=O
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.N1(CCCC1)CCN.Cl>>COC=1C=C2CCN3C(C2=CC1)=CC(=NC3=O)NCCN3CCCC3
Cl[c:14]1[cH:13][c:12]2[n:11]([c:24](=[O:25])[n:23]1)[CH2:10][CH2:9][c:7]1[c:6]-2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:8]1.[NH2:15][CH2:16][CH2:17][N:18]1[CH2:19][CH2:20][CH2:21][CH2:22]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][CH2:16][CH2:17][N:18]2[CH2:19][C...
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.NCCN1CCCC1
COc1ccc2c(c1)CCn1c-2cc(NCCN2CCCC2)nc1=O
null
null
null
Heteroatom Alkylation and Arylation
N-arylation (Buchwald-Hartwig/Ullmann-Goldberg)
c8475104970a63fce3d52b085fd15febf776cee9f570c7a80516c8bef4cb52de
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=c1nc(NCCN2CCCC2)cc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[C:10]-[C:11]-[NH2;D1;+0:12]>>[C:9]-[#7;a:5]1:[c:6](:[c:7]:[c;H0;D3;+0:1](-[NH;D2;+0:12]-[C:11]-[C:10]):[#7;a:2]:[c:3]:1=[O;D1;H0:4])-[c:8]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6, 1-a]isoquinolin-4-one (4) and 2-pyrrolidin-1-yl-ethylamine as in Example 1 d, followed by treatment with HCl. 1H-NMR (400 MHz, dB-DMSO) δ 7.64 (d, 1H), 7.59 (br, 1H), 7.00-6.92 (2H), 6.18 (s, 1H), 3.92 (t, 2H), 3.82 (s, 3H), 3.46 (m, 2H), 2...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21.C1CC[NH]C1
HCl
null
null
null
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.NCCN1CCCC1>>COc1ccc2c(c1)CCn1c-2cc(NCCN2CCCC2)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-7111dc4b01da4ae5b296add8e13344e3
CN(C)CCN.COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O>>COc1ccc2c(c1)CCn1c-2cc(NCCN(C)C)nc1=O
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.CN(CCN)C>>CN(CCNC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O)C
[NH2:15][CH2:16][CH2:17][N:18]([CH3:19])[CH3:20].Cl[c:14]1[cH:13][c:12]2[n:11]([c:22](=[O:23])[n:21]1)[CH2:10][CH2:9][c:7]1[c:6]-2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:8]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][CH2:16][CH2:17][N:18]([CH3:19])[CH3:20])[n:21][c...
CN(C)CCN.COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O
COc1ccc2c(c1)CCn1c-2cc(NCCN(C)C)nc1=O
null
null
null
Heteroatom Alkylation and Arylation
N-arylation (Buchwald-Hartwig/Ullmann-Goldberg)
c8475104970a63fce3d52b085fd15febf776cee9f570c7a80516c8bef4cb52de
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=c1nccc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[C:10]-[C:11]-[NH2;D1;+0:12]>>[C:9]-[#7;a:5]1:[c:6](:[c:7]:[c;H0;D3;+0:1](-[NH;D2;+0:12]-[C:11]-[C:10]):[#7;a:2]:[c:3]:1=[O;D1;H0:4])-[c:8]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and 2-dimethylamino-ethylamine as in Example 1 d. 1H-NMR (400 MHz, d6-DMSO) δ 7.81 (br, 1H), 7.78 (d, 1H), 7.01-6.95 (2H), 6.16 (s, 1H), 3.94 (t, 2H), 3.83 (s, 3H), 3.62 (br, 2H), 3.21 (br, 2H), 2.93 (t, 2H) and 2.8...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
HCl
null
null
null
CN(C)CCN.COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O>>COc1ccc2c(c1)CCn1c-2cc(NCCN(C)C)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-39bcad5e35974ea09b9fa16f04031455
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.NCCO>>COc1ccc2c(c1)CCn1c-2cc(NCCO)nc1=O
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.OCCN>>OCCNC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O
Cl[c:14]1[cH:13][c:12]2[n:11]([c:20](=[O:21])[n:19]1)[CH2:10][CH2:9][c:7]1[c:6]-2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:8]1.[NH2:15][CH2:16][CH2:17][OH:18]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][CH2:16][CH2:17][OH:18])[n:19][c:20]1=[O:21]
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.NCCO
COc1ccc2c(c1)CCn1c-2cc(NCCO)nc1=O
null
null
O
Heteroatom Alkylation and Arylation
N-arylation (Buchwald-Hartwig/Ullmann-Goldberg)
c8475104970a63fce3d52b085fd15febf776cee9f570c7a80516c8bef4cb52de
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=c1nccc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[C:10]-[C:11]-[NH2;D1;+0:12]>>[C:9]-[#7;a:5]1:[c:6](:[c:7]:[c;H0;D3;+0:1](-[NH;D2;+0:12]-[C:11]-[C:10]):[#7;a:2]:[c:3]:1=[O;D1;H0:4])-[c:8]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and 2-hydroxy-ethylamine as in Example 1 d. 1H-NMR (400 MHz, d6-DMSO) δ 7.62 (d 1H), 7.54 (t, 1H), 7.00-6.93 (2H), 6.17 (s, 1H), 4.85 (t, 1H), 3.91 (t, 2H), 3.82 (s, 3H) 3.50 (q, 2H), 2.91 (t, 2H) and 2H were overla...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
HCl
O
null
null
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.NCCO>O>COc1ccc2c(c1)CCn1c-2cc(NCCO)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4acff6614dbd4f5fb7a6d29c62be86a7
COc1ccc(CN)cc1.COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O>>COc1ccc(CNc2cc3n(c(=O)n2)CCc2cc(OC)ccc2-3)cc1
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.COC1=CC=C(CN)C=C1>>COC=1C=C2CCN3C(C2=CC1)=CC(=NC3=O)NCC3=CC=C(C=C3)OC
[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][NH2:8])[cH:26][cH:27]1.Cl[c:9]1[cH:10][c:11]2[n:12]([c:13](=[O:14])[n:15]1)[CH2:16][CH2:17][c:18]1[cH:19][c:20]([O:21][CH3:22])[cH:23][cH:24][c:25]1-2>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([CH2:7][NH:8][c:9]2[cH:10][c:11]3[n:12]([c:13](=[O:14])[n:15]2)[CH2:16][CH2:17][c:18]2[c...
COc1ccc(CN)cc1.COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O
COc1ccc(CNc2cc3n(c(=O)n2)CCc2cc(OC)ccc2-3)cc1
null
null
null
Heteroatom Alkylation and Arylation
N-arylation (Buchwald-Hartwig/Ullmann-Goldberg)
c8475104970a63fce3d52b085fd15febf776cee9f570c7a80516c8bef4cb52de
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=c1nc(NCc2ccccc2)cc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[NH2;D1;+0:10]-[C:11]-[c:12]>>[C:9]-[#7;a:5]1:[c:6](:[c:7]:[c;H0;D3;+0:1](-[NH;D2;+0:10]-[C:11]-[c:12]):[#7;a:2]:[c:3]:1=[O;D1;H0:4])-[c:8]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and 4-methoxy-benzylamine as in Example 1 d. 1H-NMR (400 MHz, d6-DMSO) δ 7.89 (t, 1H), 7.63 (d, 1H), 7.25 (d, 2H), 7.0-6.93 (2H), 6.90 (d, 2H), 6.16 (s, 1H), 4.45 (d, 2H), 3.92 (t, 2H), 3.82 (s, 3H), 3.73 (s, 3H) an...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccccc1.c1ccc2c(c1)CCn1cnccc21
HCl
null
null
null
COc1ccc(CN)cc1.COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O>>COc1ccc(CNc2cc3n(c(=O)n2)CCc2cc(OC)ccc2-3)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f62b863b715e41fdbb0bd864707ef00d
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.COc1cccc(CN)c1>>COc1cccc(CNc2cc3n(c(=O)n2)CCc2cc(OC)ccc2-3)c1
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.COC=1C=C(CN)C=CC1>>COC=1C=C2CCN3C(C2=CC1)=CC(=NC3=O)NCC3=CC(=CC=C3)OC
Cl[c:10]1[cH:11][c:12]2[n:13]([c:14](=[O:15])[n:16]1)[CH2:17][CH2:18][c:19]1[cH:20][c:21]([O:22][CH3:23])[cH:24][cH:25][c:26]1-2.[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][c:7]([CH2:8][NH2:9])[cH:27]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][cH:6][c:7]([CH2:8][NH:9][c:10]2[cH:11][c:12]3[n:13]([c:14](=[O:15])[n:16]2)[CH2:17][CH2:18][c...
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.COc1cccc(CN)c1
COc1cccc(CNc2cc3n(c(=O)n2)CCc2cc(OC)ccc2-3)c1
null
null
null
Heteroatom Alkylation and Arylation
N-arylation (Buchwald-Hartwig/Ullmann-Goldberg)
c8475104970a63fce3d52b085fd15febf776cee9f570c7a80516c8bef4cb52de
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=c1nc(NCc2ccccc2)cc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[NH2;D1;+0:10]-[C:11]-[c:12]>>[C:9]-[#7;a:5]1:[c:6](:[c:7]:[c;H0;D3;+0:1](-[NH;D2;+0:10]-[C:11]-[c:12]):[#7;a:2]:[c:3]:1=[O;D1;H0:4])-[c:8]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and 3-methoxy-benzylamine as in Example 1 d. 1H-NMR (400 MHz, d6-DMSO) δ 7.95 (t, 1H), 7.65 (d, 1H), 7.25 (t, 1H), 7.00-6.85 (4H), 6.82 (dd, 1H), 6.19 (s, 1H), 4.50 (d, 2H), 3.92 (t, 2H), 3.82 (s, 3H), 3.74 (s, 3H) ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccccc1.c1ccc2c(c1)CCn1cnccc21
HCl
null
null
null
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.COc1cccc(CN)c1>>COc1cccc(CNc2cc3n(c(=O)n2)CCc2cc(OC)ccc2-3)c1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-cf67d6ff22444f638f10987d1139d1ca
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1cccc([N+](=O)[O-])c1>>COc1ccc2c(c1)CCn1c-2cc(Nc2cccc([N+](=O)[O-])c2)nc1=O
ClC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.[N+](=O)([O-])C=1C=C(N)C=CC1>>[N+](=O)([O-])C=1C=C(C=CC1)NC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O
Cl[c:14]1[cH:13][c:12]2[n:11]([c:26](=[O:27])[n:25]1)[CH2:10][CH2:9][c:7]1[c:6]-2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:8]1.[NH2:15][c:16]1[cH:17][cH:18][cH:19][c:20]([N+:21](=[O:22])[O-:23])[cH:24]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][c:16]2[cH:17][cH:18][...
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1cccc([N+](=O)[O-])c1
COc1ccc2c(c1)CCn1c-2cc(Nc2cccc([N+](=O)[O-])c2)nc1=O
null
null
null
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
c8475104970a63fce3d52b085fd15febf776cee9f570c7a80516c8bef4cb52de
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
O=c1nc(Nc2ccccc2)cc2n1CCc1ccccc1-2
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](=[O;D1;H0:4]):[#7;a:5](:[c:6](:[c:7]:1)-[c:8])-[C:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[C:9]-[#7;a:5]1:[c:6](:[c:7]:[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[#7;a:2]:[c:3]:1=[O;D1;H0:4])-[c:8]
null
[]
null
null
null
null
The title compound was prepared from 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (4) and 3-nitro-aniline as in Example 1 d. 1H-NMR (400 MHz, d6-DMSO) δ 10.10 (s, 1H), 8.87 (s, 1H), 8.13 (d, 1H), 7.88 (m, 1H), 7.73 (d, 1H), 7.63 (t, 1H), 7.02 (m, 2H), 6.38 (s, 1H), 4.01 (t, 2H), 3.85 (s, 3H) and 2.99...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21
c1ccc2c(c1)CCn1cnccc21.c1ccccc1
HCl
null
null
null
COc1ccc2c(c1)CCn1c-2cc(Cl)nc1=O.Nc1cccc([N+](=O)[O-])c1>>COc1ccc2c(c1)CCn1c-2cc(Nc2cccc([N+](=O)[O-])c2)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2b11ce1c1196459d9ab1fb7188eaac05
COc1ccc2c(c1)CCn1c-2cc(Nc2cccc([N+](=O)[O-])c2)nc1=O>>COc1ccc2c(c1)CCn1c-2cc(Nc2cccc(N)c2)nc1=O
[N+](=O)([O-])C=1C=C(C=CC1)NC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.CO>>NC=1C=C(C=CC1)NC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O
O=[N+:21]([O-])[c:20]1[cH:19][cH:18][cH:17][c:16]([NH:15][c:14]2[cH:13][c:12]3[n:11]([c:24](=[O:25])[n:23]2)[CH2:10][CH2:9][c:7]2[c:6]-3[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:8]2)[cH:22]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][c:16]2[cH:17][cH:18][cH:19][c:20]...
COc1ccc2c(c1)CCn1c-2cc(Nc2cccc([N+](=O)[O-])c2)nc1=O
COc1ccc2c(c1)CCn1c-2cc(Nc2cccc(N)c2)nc1=O
null
[Zn]
CC(=O)O
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
O=c1nc(Nc2ccccc2)cc2n1CCc1ccccc1-2
O=[N+;H0;D3:1](-[O-])-[c:2](:[c:3]):[c:4]>>[NH2;D1;+0:1]-[c:2](:[c:3]):[c:4]
46
[{"value": 46.0, "product": "NC=1C=C(C=CC1)NC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O", "details": "PERCENTYIELD", "is_desired": false}, {"value": 45.9, "product": "NC=1C=C(C=CC1)NC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
To a solution of 2-(3-nitro-phenylamino)-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (5) (525.4 mg, 1.4 mmol) in AcOH (40 mL), Zn powder (ca. 300 mg) was added and stirred at room temperature for 3 hrs, then at 40° C. overnight. After cooling, MeOH was added to the mixture and insoluble materials were remove...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccc2c(c1)CCn1cnccc21.c1ccccc1
Other
[Zn].CC(=O)O
null
3
COc1ccc2c(c1)CCn1c-2cc(Nc2cccc([N+](=O)[O-])c2)nc1=O>[Zn].CC(=O)O>COc1ccc2c(c1)CCn1c-2cc(Nc2cccc(N)c2)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ea46a3d1777743fbbf413506f854f8b9
COc1ccc2c(c1)CCn1c-2cc(Nc2cccc(N)c2)nc1=O.O=C(Cl)c1cccc(Br)c1>>COc1ccc2c(c1)CCn1c-2cc(Nc2cccc(NC(=O)c3cccc(Br)c3)c2)nc1=O
NC=1C=C(C=CC1)NC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.C(C)N(CC)CC.BrC=1C=C(C(=O)Cl)C=CC1>>BrC=1C=C(C(=O)NC2=CC(=CC=C2)NC2=NC(N3C(C4=CC=C(C=C4CC3)OC)=C2)=O)C=CC1
[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][c:16]2[cH:17][cH:18][cH:19][c:20]([NH2:21])[cH:31]2)[n:32][c:33]1=[O:34].Cl[C:22](=[O:23])[c:24]1[cH:25][cH:26][cH:27][c:28]([Br:29])[cH:30]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:...
COc1ccc2c(c1)CCn1c-2cc(Nc2cccc(N)c2)nc1=O.O=C(Cl)c1cccc(Br)c1
COc1ccc2c(c1)CCn1c-2cc(Nc2cccc(NC(=O)c3cccc(Br)c3)c2)nc1=O
null
null
C1CCOC1
Acylation
Acylation of Nitrogen Nucleophiles by Acyl/Thioacyl/Carbamoyl Halides and Analogs_OS
38143a4d536201990008fd6f2c68e6571a341d1c367481869fbbbe36cb038937
0e6ae078978e324f714e184b4f72826d4e3bf2d9ab22d6e9f73740af687be16f
O=C(Nc1cccc(Nc2cc3n(c(=O)n2)CCc2ccccc2-3)c1)c1ccccc1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[NH2;D1;+0:6]-[c:7](:[c:8]):[c:9]>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[NH;D2;+0:6]-[c:7](:[c:8]):[c:9])-[c:3](:[c:4]):[c:5]
81.5
[{"value": 81.0, "product": "BrC=1C=C(C(=O)NC2=CC(=CC=C2)NC2=NC(N3C(C4=CC=C(C=C4CC3)OC)=C2)=O)C=CC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 81.5, "product": "BrC=1C=C(C(=O)NC2=CC(=CC=C2)NC2=NC(N3C(C4=CC=C(C=C4CC3)OC)=C2)=O)C=CC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
50
CELSIUS
2
HOUR
To a mixture of 2-(3-amino-phenylamino)-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (§) (20.0 mg, 0.06 mmol) in THF (2 mL), triethylamine (13 μL, 0.09 mmol) and 3-bromobenzoylchloride (10 μL, 0.07 mmol) was added and stirred at 50° C. for 2 hrs. The mixture was quenched with concentrated HCl and purified on ...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary amine
Secondary amide
null
null
c1ccc2c(c1)CCn1cnccc21.c1ccccc1.c1ccccc1
HCl
C1CCOC1
50
2
COc1ccc2c(c1)CCn1c-2cc(Nc2cccc(N)c2)nc1=O.O=C(Cl)c1cccc(Br)c1>C1CCOC1>COc1ccc2c(c1)CCn1c-2cc(Nc2cccc(NC(=O)c3cccc(Br)c3)c2)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-115897dd37cd4c5e810d7740212b0657
COc1ccc2c(c1)CCn1c-2cc(Nc2cccc(N)c2)nc1=O.O=C(Cl)C1CCCC1>>COc1ccc2c(c1)CCn1c-2cc(Nc2cccc(NC(=O)C3CCCC3)c2)nc1=O
NC=1C=C(C=CC1)NC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.C1(CCCC1)C(=O)Cl>>COC=1C=C2CCN3C(C2=CC1)=CC(=NC3=O)NC=3C=C(C=CC3)NC(=O)C3CCCC3
[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][c:16]2[cH:17][cH:18][cH:19][c:20]([NH2:21])[cH:29]2)[n:30][c:31]1=[O:32].Cl[C:22](=[O:23])[CH:24]1[CH2:25][CH2:26][CH2:27][CH2:28]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:1...
COc1ccc2c(c1)CCn1c-2cc(Nc2cccc(N)c2)nc1=O.O=C(Cl)C1CCCC1
COc1ccc2c(c1)CCn1c-2cc(Nc2cccc(NC(=O)C3CCCC3)c2)nc1=O
null
null
null
Acylation
Acylation of Nitrogen Nucleophiles by Acyl/Thioacyl/Carbamoyl Halides and Analogs_OS
38143a4d536201990008fd6f2c68e6571a341d1c367481869fbbbe36cb038937
0e6ae078978e324f714e184b4f72826d4e3bf2d9ab22d6e9f73740af687be16f
O=C(Nc1cccc(Nc2cc3n(c(=O)n2)CCc2ccccc2-3)c1)C1CCCC1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3](-[C:4])-[C:5].[NH2;D1;+0:6]-[c:7](:[c:8]):[c:9]>>[C:4]-[C:3](-[C;H0;D3;+0:1](=[O;D1;H0:2])-[NH;D2;+0:6]-[c:7](:[c:8]):[c:9])-[C:5]
null
[]
null
null
null
null
The title compound was prepared from 2-(3-amino-phenylamino)-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (6) and cyclopentanecarbonyl chloride according the method described in Example 28 c. 1H-NMR (400 MHz, d6-DMSO) δ 9.92 (s, 1H), 9.66 (br, 1H), 7.91 (s, 1H), 7.69 (d, 1H), 7.57 (br, 1H), 7.28-7.20 (2H), 7....
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary amine
Secondary amide
null
null
c1ccc2c(c1)CCn1cnccc21.c1ccccc1.C1CCCC1
HCl
null
null
null
COc1ccc2c(c1)CCn1c-2cc(Nc2cccc(N)c2)nc1=O.O=C(Cl)C1CCCC1>>COc1ccc2c(c1)CCn1c-2cc(Nc2cccc(NC(=O)C3CCCC3)c2)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-491a7ba3f81e432ebb1e348bdfdb572c
COc1ccc2c(c1)CCn1c-2cc(Nc2cccc(N)c2)nc1=O>>COc1ccc2c(c1)CCn1c-2cc(N)nc1=O
NC=1C=C(C=CC1)NC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O>>NC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O
Nc1cccc([NH:15][c:14]2[cH:13][c:12]3[n:11]([c:17](=[O:18])[n:16]2)[CH2:10][CH2:9][c:7]2[c:6]-3[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:8]2)c1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH2:15])[n:16][c:17]1=[O:18]
COc1ccc2c(c1)CCn1c-2cc(Nc2cccc(N)c2)nc1=O
COc1ccc2c(c1)CCn1c-2cc(N)nc1=O
null
null
N.CCO
Deprotection
OtherReaction
955efe56b73efe78896f5751de3370dad7e37edbc310c8e85e537e031af3ae72
71840037a637bcecd93dda6b5aa82c17bae11bfdbce0748faef9b27643e2c10a
O=c1nccc2n1CCc1ccccc1-2
N-c1:c:c:c:c(-[NH;D2;+0:1]-[c:2]2:[#7;a:3]:[c:4]:[#7;a:5]:[c:6]:[c:7]:2):c:1>>[NH2;D1;+0:1]-[c:2]1:[#7;a:3]:[c:4]:[#7;a:5]:[c:6]:[c:7]:1
105.5
[{"value": 105.5, "product": "NC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
120
CELSIUS
8
HOUR
To a suspension of 2-chloro-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (6) (919 mg, 3.5 mmol) in NH3/EtOH (7 mL) was stirred in an autoclave at 120° C. overnight. After cooling, the precipitate was filtered and washed with MeOH to give the title compound (898.3 mg, quant.). 1H-NMR (400 MHz, d6-DMSO) δ 7.99 ...
10.6084/m9.figshare.5104873.v1
null
Primary amine.Secondary amine
Primary amine
c1ccccc1
null
c1ccc2c(c1)CCn1cnccc21
Other
N.CCO
120
8
COc1ccc2c(c1)CCn1c-2cc(Nc2cccc(N)c2)nc1=O>N.CCO>COc1ccc2c(c1)CCn1c-2cc(N)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-108e0b8006264da1af16c9338792a540
COc1ccc2c(c1)CCn1c-2cc(N)nc1=O.O=C(Cl)c1c(Cl)cc(Cl)cc1Cl>>COc1ccc2c(c1)CCn1c-2cc(NC(=O)c2c(Cl)cc(Cl)cc2Cl)nc1=O
NC1=NC(N2C(C3=CC=C(C=C3CC2)OC)=C1)=O.ClC1=C(C(=O)Cl)C(=CC(=C1)Cl)Cl>>ClC1=C(C(=O)NC2=NC(N3C(C4=CC=C(C=C4CC3)OC)=C2)=O)C(=CC(=C1)Cl)Cl
[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH2:15])[n:27][c:28]1=[O:29].Cl[C:16](=[O:17])[c:18]1[c:19]([Cl:20])[cH:21][c:22]([Cl:23])[cH:24][c:25]1[Cl:26]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]2[c:7]([cH:8]1)[CH2:9][CH2:10][n:11]1[c:12]-2[cH:13][c:14]([NH:15][C:16](=[O:...
COc1ccc2c(c1)CCn1c-2cc(N)nc1=O.O=C(Cl)c1c(Cl)cc(Cl)cc1Cl
COc1ccc2c(c1)CCn1c-2cc(NC(=O)c2c(Cl)cc(Cl)cc2Cl)nc1=O
null
CN(C)C=1C=CN=CC1
C(Cl)(Cl)Cl
Acylation
Acylation of Nitrogen Nucleophiles by Acyl/Thioacyl/Carbamoyl Halides and Analogs_OS
38143a4d536201990008fd6f2c68e6571a341d1c367481869fbbbe36cb038937
0e6ae078978e324f714e184b4f72826d4e3bf2d9ab22d6e9f73740af687be16f
O=C(Nc1cc2n(c(=O)n1)CCc1ccccc1-2)c1ccccc1
Cl-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[NH2;D1;+0:6]-[c:7]1:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:[c:12]:1>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[NH;D2;+0:6]-[c:7]1:[#7;a:8]:[c:9]:[#7;a:10]:[c:11]:[c:12]:1)-[c:3](:[c:4]):[c:5]
24
[{"value": 24.0, "product": "ClC1=C(C(=O)NC2=NC(N3C(C4=CC=C(C=C4CC3)OC)=C2)=O)C(=CC(=C1)Cl)Cl", "details": "PERCENTYIELD", "is_desired": false}, {"value": 23.7, "product": "ClC1=C(C(=O)NC2=NC(N3C(C4=CC=C(C=C4CC3)OC)=C2)=O)C(=CC(=C1)Cl)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
25
CELSIUS
8
HOUR
To a suspension of 2-amino-9-methoxy-6,7-dihydro-pyrimido[6,1-a]isoquinolin-4-one (7) (40 mg, 0.16 mmol) in CHCl3 (3 mL), DMAP (30.1 mg, 0.24 mmol) and 2,4,6-trichlorobenzoyl chloride (37.5 uL, 0.24 mmol) was added and stirred at 25° C. overnight. After cooling, the mixture was purified on BondElut® SCX (Varian Incorpo...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary amine
Secondary amide
null
null
c1ccc2c(c1)CCn1cnccc21.c1ccccc1
HCl
CN(C)C=1C=CN=CC1.C(Cl)(Cl)Cl
25
8
COc1ccc2c(c1)CCn1c-2cc(N)nc1=O.O=C(Cl)c1c(Cl)cc(Cl)cc1Cl>CN(C)C=1C=CN=CC1.C(Cl)(Cl)Cl>COc1ccc2c(c1)CCn1c-2cc(NC(=O)c2c(Cl)cc(Cl)cc2Cl)nc1=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-0acb0b6fd4e84fcfbd9ddc5057e095ed
COc1ccc(C(=O)OCC2CC2CBr)cc1.[C-]#N>>COc1ccc(C(=O)OCC2(CC#N)CC2)cc1
COC1=CC=C(C(=O)OCC2C(C2)CBr)C=C1.[C-]#N.[K+].C([O-])(O)=O.[Na+]>>COC1=CC=C(C(=O)OCC2(CC2)CC#N)C=C1
Br[CH2:15][CH:16]1[CH:11]([CH2:10][O:9][C:7]([c:6]2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:18][cH:17]2)=[O:8])[CH2:12]1.[C-:13]#[N:14]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6]([C:7](=[O:8])[O:9][CH2:10][C:11]2([CH2:12][C:13]#[N:14])[CH2:15][CH2:16]2)[cH:17][cH:18]1
COc1ccc(C(=O)OCC2CC2CBr)cc1.[C-]#N
COc1ccc(C(=O)OCC2(CC#N)CC2)cc1
null
null
O.C(C)O
C-C Coupling
OtherReaction
ab6bf26f9886a8d1b65eb4801b5d4f33196eb2fe0f1cd4ce637f89e29c0a4643
1dbefa1fc17e03074aa3f6619987f71dfa9a1cb0d61de142a880cd3f05e4f004
O=C(OCC1CC1)c1ccccc1
Br-[CH2;D2;+0:1]-[CH;D3;+0:2]1-[CH2;D2;+0:3]-[CH;D3;+0:4]-1-[C:5]-[#8:6]-[C:7]=[O;D1;H0:8].[C-;H0;D1:9]#[N;D1;H0:10]>>[N;D1;H0:10]#[C;H0;D2;+0:9]-[CH2;D2;+0:3]-[C;H0;D4;+0:4]1(-[C:5]-[#8:6]-[C:7]=[O;D1;H0:8])-[CH2;D2;+0:1]-[CH2;D2;+0:2]-1
null
[]
35
CELSIUS
2
DAY
261 mg of compound 10a was dissolved in 5 ml ethanol. A solution of 98 mg potassium cyanide in 5 ml water was added and the mixture was stirred at 35° C. for two days. 10 ml of a saturated aqueous sodium bicarbonate was added. The mixture was extracted twice with ethyl acetate. The combined extracts were dried with sod...
10.6084/m9.figshare.5104873.v1
null
Primary halide
Nitrile
C1CC1
C1CC1
c1ccccc1.C1CC1
Br-
O.C(C)O
35
48
COc1ccc(C(=O)OCC2CC2CBr)cc1.[C-]#N>O.C(C)O>COc1ccc(C(=O)OCC2(CC#N)CC2)cc1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f224ec6f8a7b411681d41b4cca8facae
COc1cc2c(Cl)c(C#N)cnc2cc1OCCCCl.Nc1c(Cl)ccc2c1OCO2>>COc1cc2c(Nc3c(Cl)ccc4c3OCO4)c(C#N)cnc2cc1OCCCCl
C[Si](N[Si](C)(C)C)(C)C.[Na].ClC1=CC=C2C(=C1N)OCO2.ClC1=C(C=NC2=CC(=C(C=C12)OC)OCCCCl)C#N>>ClC1=CC=C2C(=C1NC1=C(C=NC3=CC(=C(C=C13)OC)OCCCCl)C#N)OCO2
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][Cl:30])[cH:24][c:23]2[n:22][cH:21][c:18]1[C:19]#[N:20].[NH2:7][c:8]1[c:9]([Cl:10])[cH:11][cH:12][c:13]2[c:14]1[O:15][CH2:16][O:17]2>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]3[c:9]([Cl:10])[cH:11][cH:12][c:13]4[c:14]3[O:15][CH2:16][O:17]...
COc1cc2c(Cl)c(C#N)cnc2cc1OCCCCl.Nc1c(Cl)ccc2c1OCO2
COc1cc2c(Nc3c(Cl)ccc4c3OCO4)c(C#N)cnc2cc1OCCCCl
null
null
O.CN(C)C=O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
45e8470a78418ade39424f40732aa5ecf6717a7e5d47830a67429c5970ebd551
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cc(Nc2ccnc3ccccc23)c2c(c1)OCO2
Cl-[c;H0;D3;+0:1]1:[c:2](-[C:3]#[N;D1;H0:4]):[c:5]:[#7;a:6]:[c:7](:[c:8]):[c:9]:1:[c:10].[#8:11]-[c:12]:[c:13](-[NH2;D1;+0:14]):[c:15]>>[#8:11]-[c:12]:[c:13](-[NH;D2;+0:14]-[c;H0;D3;+0:1]1:[c:2](-[C:3]#[N;D1;H0:4]):[c:5]:[#7;a:6]:[c:7](:[c:8]):[c:9]:1:[c:10]):[c:15]
86.5
[{"value": 86.5, "product": "ClC1=CC=C2C(=C1NC1=C(C=NC3=CC(=C(C=C13)OC)OCCCCl)C#N)OCO2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
5
MINUTE
Sodium hexamethyldisilazane (1M solution in THF; 3.34 ml) was added to a solution of 6-chloro-2,3-methylenedioxyaniline (0.573 g) in DMF (12 ml) that was cooled to 0° C. and the mixture was stirred for 5 minutes. A solution of 4-chloro-7-(3-chloropropoxy)-3-cyano-6-methoxyquinoline (0.5 g) in DMF (3 ml) was added and t...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncccc2c1
c1ccc2ncccc2c1
c1ccc2c(c1)OCO2.c1ccc2ncccc2c1
HCl
O.CN(C)C=O
0
0.083333
COc1cc2c(Cl)c(C#N)cnc2cc1OCCCCl.Nc1c(Cl)ccc2c1OCO2>O.CN(C)C=O>COc1cc2c(Nc3c(Cl)ccc4c3OCO4)c(C#N)cnc2cc1OCCCCl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a45a50c6621a4e088906e4c8c0cd3295
CO.O=C(O)c1cccc(O)c1O>>COC(=O)c1cccc(O)c1O
OC1=C(C(=O)O)C=CC=C1O.CO>>OC1=C(C(=O)OC)C=CC=C1O
[CH3:1][OH:2].O[C:3](=[O:4])[c:5]1[cH:6][cH:7][cH:8][c:9]([OH:10])[c:11]1[OH:12]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][cH:8][c:9]([OH:10])[c:11]1[OH:12]
CO.O=C(O)c1cccc(O)c1O
COC(=O)c1cccc(O)c1O
null
S(O)(O)(=O)=O
null
Protection
Esterification of Carboxylic Acids
9cecdbd189c6f9c3648521d17154d013842a5498de4e76e65efb1d842973340b
af0b8064f2e82ebe66c4c29d2391785ac1b993104265ccdc4d67ca79e36fa3c8
c1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C;D1;H3:6]-[OH;D1;+0:7]>>[C;D1;H3:6]-[O;H0;D2;+0:7]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
null
[]
60
CELSIUS
null
null
A mixture of 2,3-dihydroxybenzoic acid (5 g), methanol (50 ml) and concentrated sulphuric acid (10 drops) was stirred and heated to 60° C. for 24 hours. The mixture was evaporated and the residue was taken up in ethyl acetate. The organic solution was washed with a saturated solution of sodium bicarbonate, dried over m...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Methanol
Ester
null
null
c1ccccc1
HO-
S(O)(O)(=O)=O
60
null
CO.O=C(O)c1cccc(O)c1O>S(O)(O)(=O)=O>COC(=O)c1cccc(O)c1O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a69c7a0cf7e74c18b0e09732f80e77bf
COc1cc2c(Cl)c(C#N)cnc2cc1O.Nc1cccc2c1OCO2>>COc1cc2c(Nc3cccc4c3OCO4)c(C#N)cnc2cc1O
ClC1=C(C=NC2=CC(=C(C=C12)OC)O)C#N.C1OC2=C(N)C=CC=C2O1>>C(#N)C=1C=NC2=CC(=C(C=C2C1NC1=C2C(=CC=C1)OCO2)OC)O
Cl[c:6]1[c:5]2[cH:4][c:3]([O:2][CH3:1])[c:24]([OH:25])[cH:23][c:22]2[n:21][cH:20][c:17]1[C:18]#[N:19].[NH2:7][c:8]1[cH:9][cH:10][cH:11][c:12]2[c:13]1[O:14][CH2:15][O:16]2>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]3[cH:9][cH:10][cH:11][c:12]4[c:13]3[O:14][CH2:15][O:16]4)[c:17]([C:18]#[N:19])[cH:20][n:21][c:22]2[cH...
COc1cc2c(Cl)c(C#N)cnc2cc1O.Nc1cccc2c1OCO2
COc1cc2c(Nc3cccc4c3OCO4)c(C#N)cnc2cc1O
null
null
C(CC)O
Heteroatom Alkylation and Arylation
Goldberg coupling aryl amine-aryl chloride
45e8470a78418ade39424f40732aa5ecf6717a7e5d47830a67429c5970ebd551
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cc(Nc2ccnc3ccccc23)c2c(c1)OCO2
Cl-[c;H0;D3;+0:1]1:[c:2](-[C:3]#[N;D1;H0:4]):[c:5]:[#7;a:6]:[c:7](:[c:8]):[c:9]:1:[c:10].[#8:11]-[c:12]:[c:13](-[NH2;D1;+0:14]):[c:15]>>[#8:11]-[c:12]:[c:13](-[NH;D2;+0:14]-[c;H0;D3;+0:1]1:[c:2](-[C:3]#[N;D1;H0:4]):[c:5]:[#7;a:6]:[c:7](:[c:8]):[c:9]:1:[c:10]):[c:15]
null
[]
115
CELSIUS
null
null
A mixture of 4-chloro-3-cyano-7-hydroxy-6-methoxyquinoline (5 g), 2,3-methylenedioxyaniline (3.07 g) and propanol (100 ml) was stirred and heated to 115° C. for 18 hours. The resultant precipitate was isolated, washed in turn with propanol and diethyl ether and dried under vacuum. There was thus obtained the title comp...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccc2ncccc2c1
c1ccc2ncccc2c1
c1ccc2c(c1)OCO2.c1ccc2ncccc2c1
HCl
C(CC)O
115
null
COc1cc2c(Cl)c(C#N)cnc2cc1O.Nc1cccc2c1OCO2>C(CC)O>COc1cc2c(Nc3cccc4c3OCO4)c(C#N)cnc2cc1O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-cd01101c1137484d92df54c3e56ba1c6
COc1cc2c(Nc3cccc4c3OCO4)c(C#N)cnc2cc1O.OCCBr>>COc1cc2c(Nc3cccc4c3OCO4)c(C#N)cnc2cc1OCCBr
C(#N)C=1C=NC2=CC(=C(C=C2C1NC1=C2C(=CC=C1)OCO2)OC)O.BrCCO>>BrCCOC1=C(C=C2C(=C(C=NC2=C1)C#N)NC1=C2C(=CC=C1)OCO2)OC
[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]3[cH:9][cH:10][cH:11][c:12]4[c:13]3[O:14][CH2:15][O:16]4)[c:17]([C:18]#[N:19])[cH:20][n:21][c:22]2[cH:23][c:24]1[OH:25].O[CH2:26][CH2:27][Br:28]>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]3[cH:9][cH:10][cH:11][c:12]4[c:13]3[O:14][CH2:15][O:16]4)[c:17]([C:18]#[N:19])[c...
COc1cc2c(Nc3cccc4c3OCO4)c(C#N)cnc2cc1O.OCCBr
COc1cc2c(Nc3cccc4c3OCO4)c(C#N)cnc2cc1OCCBr
null
null
null
Heteroatom Alkylation and Arylation
Mitsunobu aryl ether
86bfb73617450d22f9456ed5ce4d96a73f1f8fc0c016bebae57fda68e2da86a2
2258bd14c3b5449b92dc09cf9fa522f88d5071b4af20f7e968b60aa1ae6db0cf
c1cc(Nc2ccnc3ccccc23)c2c(c1)OCO2
O-[CH2;D2;+0:1]-[C:2]-[Br;D1;H0:3].[#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]-[Br;D1;H0:3]):[c:9]
82
[{"value": 82.0, "product": "BrCCOC1=C(C=C2C(=C(C=NC2=C1)C#N)NC1=C2C(=CC=C1)OCO2)OC", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 8, 3-cyano-7-hydroxy-6-methoxy-4-(2,3-methylenedioxyanilino)quinoline was reacted with 2-bromoethanol to give the title compound in 82% yield; NMR Spectrum: (DMSOd6) 3.88 (t, 2H), 3.94 (s, 3H), 4.51 (t, 2H), 5.96 (s, 2H), 6.8-6.93 (m, 3H), 7.34 (s, 1H), 7.8 (s, ...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol.Aromatic alcohol
Ether
null
null
c1ccc2c(c1)OCO2.c1ccc2ncccc2c1
HO-
null
null
null
COc1cc2c(Nc3cccc4c3OCO4)c(C#N)cnc2cc1O.OCCBr>>COc1cc2c(Nc3cccc4c3OCO4)c(C#N)cnc2cc1OCCBr
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-02299f06a64e41adb6ac5ef29d0c9252
C1COCCN1.COc1cc2c(Nc3cccc4c3OCO4)c(C#N)cnc2cc1OC[C@H]1CO1>>COc1cc2c(Nc3cccc4c3OCO4)c(C#N)cnc2cc1OC[C@H](O)CN1CCOCC1
C(#N)C=1C=NC2=CC(=C(C=C2C1NC1=C2C(=CC=C1)OCO2)OC)OC[C@H]2CO2.N1CCOCC1>>C(#N)C=1C=NC2=CC(=C(C=C2C1NC1=C2C(=CC=C1)OCO2)OC)OC[C@@H](CN2CCOCC2)O
[NH:30]1[CH2:31][CH2:32][O:33][CH2:34][CH2:35]1.[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]3[cH:9][cH:10][cH:11][c:12]4[c:13]3[O:14][CH2:15][O:16]4)[c:17]([C:18]#[N:19])[cH:20][n:21][c:22]2[cH:23][c:24]1[O:25][CH2:26][C@@H:27]1[O:28][CH2:29]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]3[cH:9][cH:10][cH:11][c:1...
C1COCCN1.COc1cc2c(Nc3cccc4c3OCO4)c(C#N)cnc2cc1OC[C@H]1CO1
COc1cc2c(Nc3cccc4c3OCO4)c(C#N)cnc2cc1OC[C@H](O)CN1CCOCC1
null
null
C(CC)O
Heteroatom Alkylation and Arylation
Ring opening of epoxide with amine
851dfc16280bb8f11cdb75741b500ca1a156bb53c804ef98fc4ef4b1d0f67de0
97e758d6c4c8255d25541eb6c6a6f62e7dc30829ea162ca3392731efabc98a65
c1cc(Nc2ccnc3cc(OCCCN4CCOCC4)ccc23)c2c(c1)OCO2
[#8:1]-[C:2]-[C@H;D3;+0:3]1-[CH2;D2;+0:4]-[O;H0;D2;+0:5]-1.[#8:6]1-[C:7]-[C:8]-[NH;D2;+0:9]-[C:10]-[C:11]-1>>[#8:1]-[C:2]-[C@H;D3;+0:3](-[OH;D1;+0:5])-[CH2;D2;+0:4]-[N;H0;D3;+0:9]1-[C:8]-[C:7]-[#8:6]-[C:11]-[C:10]-1
32.7
[{"value": 32.7, "product": "C(#N)C=1C=NC2=CC(=C(C=C2C1NC1=C2C(=CC=C1)OCO2)OC)OC[C@@H](CN2CCOCC2)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
null
null
A mixture of 3-cyano-7-[(2R)-2,3-epoxypropoxy]-6-methoxy-4-(2,3-methylenedioxyanilino)quinoline (0.1 g), morpholine (0.11 g) and propanol (5 ml) was stirred and heated to 80° C. for 3 hours. The resultant mixture was evaporated and the residue was purified by column chromatography on silica using increasingly polar mix...
10.6084/m9.figshare.5104873.v1
null
Ether.Secondary amine
Secondary alcohol.Tertiary amine
C1COCCN1.C1CO1
C1COCC[NH]1
c1ccc2c(c1)OCO2.c1ccc2ncccc2c1.C1COCC[NH]1
null
C(CC)O
80
null
C1COCCN1.COc1cc2c(Nc3cccc4c3OCO4)c(C#N)cnc2cc1OC[C@H]1CO1>C(CC)O>COc1cc2c(Nc3cccc4c3OCO4)c(C#N)cnc2cc1OC[C@H](O)CN1CCOCC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-e3042368d58241b8a674e5808d2771c7
CC(=O)N1CCNCC1.COc1cc2c(Nc3cccc4c3OCO4)c(C#N)cnc2cc1OC[C@H]1CO1>>COc1cc2c(Nc3cccc4c3OCO4)c(C#N)cnc2cc1OC[C@H](O)CN1CCN(C(C)=O)CC1
C(#N)C=1C=NC2=CC(=C(C=C2C1NC1=C2C(=CC=C1)OCO2)OC)OC[C@H]2CO2.C(C)(=O)N1CCNCC1>>C(C)(=O)N1CCN(CC1)C[C@H](COC1=C(C=C2C(=C(C=NC2=C1)C#N)NC1=C2C(=CC=C1)OCO2)OC)O
[NH:30]1[CH2:31][CH2:32][N:33]([C:34]([CH3:35])=[O:36])[CH2:37][CH2:38]1.[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]3[cH:9][cH:10][cH:11][c:12]4[c:13]3[O:14][CH2:15][O:16]4)[c:17]([C:18]#[N:19])[cH:20][n:21][c:22]2[cH:23][c:24]1[O:25][CH2:26][C@@H:27]1[O:28][CH2:29]1>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([NH:7][c:8]...
CC(=O)N1CCNCC1.COc1cc2c(Nc3cccc4c3OCO4)c(C#N)cnc2cc1OC[C@H]1CO1
COc1cc2c(Nc3cccc4c3OCO4)c(C#N)cnc2cc1OC[C@H](O)CN1CCN(C(C)=O)CC1
null
null
null
Heteroatom Alkylation and Arylation
Ring opening of epoxide with amine
17ab6d3921429d49d85a9af124942b034c73e1fe2f69930f0392bbbfc9046e12
97e758d6c4c8255d25541eb6c6a6f62e7dc30829ea162ca3392731efabc98a65
c1cc(Nc2ccnc3cc(OCCCN4CCNCC4)ccc23)c2c(c1)OCO2
[#7:1]1-[C:2]-[C:3]-[NH;D2;+0:4]-[C:5]-[C:6]-1.[#8:7]-[C:8]-[C@H;D3;+0:9]1-[CH2;D2;+0:10]-[O;H0;D2;+0:11]-1>>[#8:7]-[C:8]-[C@H;D3;+0:9](-[OH;D1;+0:11])-[CH2;D2;+0:10]-[N;H0;D3;+0:4]1-[C:3]-[C:2]-[#7:1]-[C:6]-[C:5]-1
35
[{"value": 35.0, "product": "C(C)(=O)N1CCN(CC1)C[C@H](COC1=C(C=C2C(=C(C=NC2=C1)C#N)NC1=C2C(=CC=C1)OCO2)OC)O", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 11, 3-cyano-7-[(2R)-2,3-epoxypropoxy]-6-methoxy-4-(2,3-methylenedioxyanilino)quinoline was reacted with 1-acetylpiperazine to give the title compound in 35% yield; NMR Spectrum: (DMSOd6) 1.96 (s, 3H), 2.34-2.54 (m, 6H), 3.35-3.45 (m, 4H), 3.94 (s, 3H), 4.0-4.1 (...
10.6084/m9.figshare.5104873.v1
null
Ether.Secondary amine
Secondary alcohol.Tertiary amine
C1CNCC[NH]1.C1CO1
C1C[NH]CC[NH]1
c1ccc2c(c1)OCO2.c1ccc2ncccc2c1.C1C[NH]CC[NH]1
null
null
null
null
CC(=O)N1CCNCC1.COc1cc2c(Nc3cccc4c3OCO4)c(C#N)cnc2cc1OC[C@H]1CO1>>COc1cc2c(Nc3cccc4c3OCO4)c(C#N)cnc2cc1OC[C@H](O)CN1CCN(C(C)=O)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a5d66199e62444b397bafa9b4178fe74
COc1cc2c(Cl)c(C#N)cnc2cc1OCCCN1CCN(C)CC1.Oc1cccc2c1OCO2>>COc1cc2c(Oc3cccc4c3OCO4)c(C#N)cnc2cc1OCCCN1CCN(C)CC1
C([O-])([O-])=O.[K+].[K+].C1OC2=C(C=CC=C2O1)O.ClC1=C(C=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C)C#N>>C(#N)C=1C=NC2=CC(=C(C=C2C1OC1=C2C(=CC=C1)OCO2)OC)OCCCN2CCN(CC2)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][c:17]1[C:18]#[N:19].[OH:7][c:8]1[cH:9][cH:10][cH:11][c:12]2[c:13]1[O:14][CH2:15][O:16]2>>[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:...
COc1cc2c(Cl)c(C#N)cnc2cc1OCCCN1CCN(C)CC1.Oc1cccc2c1OCO2
COc1cc2c(Oc3cccc4c3OCO4)c(C#N)cnc2cc1OCCCN1CCN(C)CC1
null
null
CN(C)C=O
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
499018af6792b58a137ac4495e0c20acdc548a3418ba695c815cb38084ffd839
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1cc2c(c(Oc3ccnc4cc(OCCCN5CCNCC5)ccc34)c1)OCO2
Cl-[c;H0;D3;+0:1]1:[c:2](-[C:3]#[N;D1;H0:4]):[c:5]:[#7;a:6]:[c:7](:[c:8]):[c:9]:1:[c:10].[#8:11]-[c:12]:[c:13](-[OH;D1;+0:14]):[c:15]>>[#8:11]-[c:12]:[c:13](-[O;H0;D2;+0:14]-[c;H0;D3;+0:1]1:[c:2](-[C:3]#[N;D1;H0:4]):[c:5]:[#7;a:6]:[c:7](:[c:8]):[c:9]:1:[c:10]):[c:15]
54.3
[{"value": 54.3, "product": "C(#N)C=1C=NC2=CC(=C(C=C2C1OC1=C2C(=CC=C1)OCO2)OC)OCCCN2CCN(CC2)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
10
MINUTE
Potassium carbonate-(0.055 g) was added to a solution of 2,3-methylenedioxyphenol (0.041 g) in DMF (3 ml) and the mixture was stirred at ambient temperature for 10 minutes. 4-Chloro-3-cyano-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline (0.1 g) was added and the mixture was stirred and heated to 95° C. for 2 ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncccc2c1
c1ccc2ncccc2c1
c1ccc2c(c1)OCO2.c1ccc2ncccc2c1.C1C[NH]CC[NH]1
HCl
CN(C)C=O
null
0.166667
COc1cc2c(Cl)c(C#N)cnc2cc1OCCCN1CCN(C)CC1.Oc1cccc2c1OCO2>CN(C)C=O>COc1cc2c(Oc3cccc4c3OCO4)c(C#N)cnc2cc1OCCCN1CCN(C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-98ec8661d4f34030b2211a3fe72e4ddc
CN1CCNCC1.OCCCBr>>CN1CCN(CCCO)CC1
BrCCCO.CN1CCNCC1.C([O-])([O-])=O.[K+].[K+]>>OCCCN1CCN(CC1)C
[CH3:1][N:2]1[CH2:3][CH2:4][NH:5][CH2:10][CH2:11]1.Br[CH2:6][CH2:7][CH2:8][OH:9]>>[CH3:1][N:2]1[CH2:3][CH2:4][N:5]([CH2:6][CH2:7][CH2:8][OH:9])[CH2:10][CH2:11]1
CN1CCNCC1.OCCCBr
CN1CCN(CCCO)CC1
null
null
C(C)O
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
b703623ddc3b029d4716c15f5414f41773434bcc7e3f3853faf62273596bed77
523d37155b42c8dc851abeddadebb241cdd90bdf649ba750c35e13c8c752d7b0
C1CNCCN1
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
null
[]
null
null
null
null
A mixture of 3-bromopropanol (20 ml), N-methylpiperazine (29 ml), potassium carbonate (83 g) and ethanol (200 ml) was stirred and heated to reflux for 20 hours. The mixture was cooled to ambient temperature and filtered. The filtrate was evaporated and the residue was triturated under diethyl ether. The resultant mixtu...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary amine
Tertiary amine
C1C[NH]CCN1
C1C[NH]CC[NH]1
C1C[NH]CC[NH]1
HBr
C(C)O
null
null
CN1CCNCC1.OCCCBr>C(C)O>CN1CCN(CCCO)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3944141735ad4ac9aaabaa3d9eb6575c
COc1cc2c(Cl)c(C#N)cnc2cc1OCCCN1CCN(C)CC1.Oc1c(Br)ccc2c1OCO2>>COc1cc2c(Oc3c(Br)ccc4c3OCO4)c(C#N)cnc2cc1OCCCN1CCN(C)CC1
ClC1=C(C=NC2=CC(=C(C=C12)OC)OCCCN1CCN(CC1)C)C#N.BrC1=CC=C2C(=C1O)OCO2>>BrC1=CC=C2C(=C1OC1=C(C=NC3=CC(=C(C=C13)OC)OCCCN1CCN(CC1)C)C#N)OCO2
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][N:33]([CH3:34])[CH2:35][CH2:36]3)[cH:24][c:23]2[n:22][cH:21][c:18]1[C:19]#[N:20].[OH:7][c:8]1[c:9]([Br:10])[cH:11][cH:12][c:13]2[c:14]1[O:15][CH2:16][O:17]2>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[c:6]([O:7][c:8]3[c:9]([Br:10])[...
COc1cc2c(Cl)c(C#N)cnc2cc1OCCCN1CCN(C)CC1.Oc1c(Br)ccc2c1OCO2
COc1cc2c(Oc3c(Br)ccc4c3OCO4)c(C#N)cnc2cc1OCCCN1CCN(C)CC1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
499018af6792b58a137ac4495e0c20acdc548a3418ba695c815cb38084ffd839
27e9a6bab4e3ed54aeb6be4d84cb1c0170208288795e252a46e57e44ecc064f0
c1cc2c(c(Oc3ccnc4cc(OCCCN5CCNCC5)ccc34)c1)OCO2
Cl-[c;H0;D3;+0:1]1:[c:2](-[C:3]#[N;D1;H0:4]):[c:5]:[#7;a:6]:[c:7](:[c:8]):[c:9]:1:[c:10].[#8:11]-[c:12]:[c:13](-[OH;D1;+0:14]):[c:15]>>[#8:11]-[c:12]:[c:13](-[O;H0;D2;+0:14]-[c;H0;D3;+0:1]1:[c:2](-[C:3]#[N;D1;H0:4]):[c:5]:[#7;a:6]:[c:7](:[c:8]):[c:9]:1:[c:10]):[c:15]
52
[{"value": 52.0, "product": "BrC1=CC=C2C(=C1OC1=C(C=NC3=CC(=C(C=C13)OC)OCCCN1CCN(CC1)C)C#N)OCO2", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Using an analogous procedure to that described in Example 14, 4chloro-3-cyano-6-methoxy-7-[3-(4-methylpiperazin-1-yl)propoxy]quinoline was reacted with 6-bromo-2,3-methylenedioxyphenol to give the title compound as a solid in 52% yield; NMR Spectrum: (DMSOd6 and CF3CO2D) 2.25-2.4 (m, 2H), 2.95 (s, 3H), 3.24-4.0 (m, 8H)...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic alcohol
Ether
c1ccc2ncccc2c1
c1ccc2ncccc2c1
c1ccc2c(c1)OCO2.c1ccc2ncccc2c1.C1C[NH]CC[NH]1
HCl
null
null
null
COc1cc2c(Cl)c(C#N)cnc2cc1OCCCN1CCN(C)CC1.Oc1c(Br)ccc2c1OCO2>>COc1cc2c(Oc3c(Br)ccc4c3OCO4)c(C#N)cnc2cc1OCCCN1CCN(C)CC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-73684015d8eb4a0593744711924a72c2
COc1cc2ncc(C#N)c(Nc3c(I)cc(I)c4c3OCO4)c2cc1OC.COc1cc2ncc(C#N)c(Nc3c(I)ccc4c3OCO4)c2cc1OC>>COc1cc2ncc(C#N)c(Nc3c(C#N)ccc4c3OCO4)c2cc1OC
C(#N)C=1C=NC2=CC(=C(C=C2C1NC1=C2C(=CC=C1I)OCO2)OC)OC.C(#N)C=1C=NC2=CC(=C(C=C2C1NC1=C2C(=C(C=C1I)I)OCO2)OC)OC>>C(#N)C=1C=NC2=CC(=C(C=C2C1NC1=C2C(=CC=C1C#N)OCO2)OC)OC
I[c:14]1[c:13]([NH:12][c:11]2[c:8]([C:9]#[N:10])[cH:7][n:6][c:5]3[cH:4][c:3]([O:2][CH3:1])[c:26]([O:27][CH3:28])[cH:25][c:24]32)[c:20]2[c:19]([c:18](I)[cH:17]1)[O:23][CH2:22][O:21]2.COc1cc2ncc([C:15]#[N:16])c(Nc3c(I)ccc4c3OCO4)c2cc1OC>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[n:6][cH:7][c:8]([C:9]#[N:10])[c:11]([NH:12][c:13]3[c:...
COc1cc2ncc(C#N)c(Nc3c(I)cc(I)c4c3OCO4)c2cc1OC.COc1cc2ncc(C#N)c(Nc3c(I)ccc4c3OCO4)c2cc1OC
COc1cc2ncc(C#N)c(Nc3c(C#N)ccc4c3OCO4)c2cc1OC
null
C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd].[C-]#N.[Zn+2].[C-]#N.C1(=CC=CC=C1)P(C1=CC=CC=C1)[C-]1C=CC=C1.[CH-]1C=CC=C1.[Fe+2].[Zn]
CC(=O)N(C)C
C-C Coupling
OtherReaction
6e71d68a19a9c1405b1740f1d7d34d696cc355fb6e2f5b9734b3a5806431ff9e
4879b197a369623a5eec53ab3e96948572566aae2614433d35281c86c0a600b3
c1cc(Nc2ccnc3ccccc23)c2c(c1)OCO2
C-O-c1:c:c2:n:c:c(-[C;H0;D2;+0:1]#[N;D1;H0:2]):c(-N-c3:c(-I):c:c:c4:c:3-O-C-O-4):c:2:c:c:1-O-C.I-[c;H0;D3;+0:3]1:[c:4]:[c;H0;D3;+0:5](-I):[c:6]2:[c:7](:[c:8]:1-[#7:9])-[#8:10]-[C:11]-[#8:12]-2>>[#7:9]-[c:8]1:[c:7]2:[c:6](:[cH;D2;+0:5]:[c:4]:[c;H0;D3;+0:3]:1-[C;H0;D2;+0:1]#[N;D1;H0:2])-[#8:12]-[C:11]-[#8:10]-2
null
[]
110
CELSIUS
null
null
Tris(dibenzylideneacetone)dipalladium (0.039 g) was added to a mixture of a 4:1 mixture (0.25 g) of 3-cyano-4-(6-iodo-2,3-methylenedioxyanilino)-6,7-dimethoxyquinoline and 3-cyano-4-(4,6-diiodo-2,3-methylenedioxyanilino)-6,7-dimethoxyquinoline (Example 10, Note [11]), zinc cyanide (0.092 g), diphenylphosphinoferrocene ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Aromatic halide.Ether.Ether.Ether.Ether.Nitrile.Secondary amine
Nitrile
c1ccc2c(c1)OCO2.c1ccc2ncccc2c1.c1ccc2c(c1)OCO2
c1ccc2c(c1)OCO2
c1ccc2ncccc2c1.c1ccc2c(c1)OCO2
HI
C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd].[C-]#N.[Zn+2].[C-]#N.C1(=CC=CC=C1)P(C1=CC=CC=C1)[C-]1C=CC=C1.[CH-]1C=CC=C1.[Fe+2].[Zn].CC(=O)N(C)C
110
null
COc1cc2ncc(C#N)c(Nc3c(I)cc(I)c4c3OCO4)c2cc1OC.COc1cc2ncc(C#N)c(Nc3c(I)ccc4c3OCO4)c2cc1OC>C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd].[C-]#N.[Zn+2].[C-]#N.C1(=CC=CC=C1)P(C1=CC=CC=C1)[C-]1C=CC=C1.[CH-]1C=CC=C1.[Fe+2].[Zn].CC(=O)N(C)C>CO...
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3184a89c183a481bbd9ff639d1b3d240
COc1cc2ncc(C#N)c(Nc3ccc(I)c4c3OCO4)c2cc1OC>>COc1cc2ncc(C#N)c(Nc3ccc(C#N)c4c3OCO4)c2cc1OC
C(#N)C=1C=NC2=CC(=C(C=C2C1NC1=C2C(=C(C=C1)I)OCO2)OC)OC.CC(=O)N(C)C>>C(#N)C=1C=NC2=CC(=C(C=C2C1NC1=C2C(=C(C=C1)C#N)OCO2)OC)OC
I[c:16]1[cH:15][cH:14][c:13]([NH:12][c:11]2[c:8]([C:9]#[N:10])[cH:7][n:6][c:5]3[cH:4][c:3]([O:2][CH3:1])[c:26]([O:27][CH3:28])[cH:25][c:24]32)[c:20]2[c:19]1[O:23][CH2:22][O:21]2>>[CH3:1][O:2][c:3]1[cH:4][c:5]2[n:6][cH:7][c:8]([C:9]#[N:10])[c:11]([NH:12][c:13]3[cH:14][cH:15][c:16]([C:17]#[N:18])[c:19]4[c:20]3[O:21][CH2:...
COc1cc2ncc(C#N)c(Nc3ccc(I)c4c3OCO4)c2cc1OC
COc1cc2ncc(C#N)c(Nc3ccc(C#N)c4c3OCO4)c2cc1OC
null
C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd].C1(=CC=CC=C1)P(C1=CC=CC=C1)[C-]1C=CC=C1.[CH-]1C=CC=C1.[Fe+2].[Zn]
null
Miscellaneous
OtherReaction
fb09649fd435e8f138dc0d7d983f4e059a414c031c70823708ee750a9e6b44c8
73a96fe5e833259ca394a42f82d6cc2ee7231bcde92d95030d2893b90c3fef76
c1cc(Nc2ccnc3ccccc23)c2c(c1)OCO2
I-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]1:[c:5]-[#8:6]-[C:7]-[#8:8]-1>>[N;D1;H0:9]#[C:10]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]1:[c:5]-[#8:6]-[C:7]-[#8:8]-1
null
[]
110
CELSIUS
null
null
Tris(dibenzylideneacetone)dipalladium (0.0073 g) was added to a mixture of 3-cyano-4-(4-iodo-2,3methylenedioxyanilino)-6,7-dimethoxyquinoline (0.05 g) zinc cyanide (0.015 g), diphenylphosphinoferrocene (0.009 g), zinc powder (0.0035 g) and DMA (2 ml) and the resultant mixture was stirred and heated to 110° C. for 1 hou...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
Nitrile
c1ccc2c(c1)OCO2
c1ccc2c(c1)OCO2
c1ccc2ncccc2c1.c1ccc2c(c1)OCO2
I-
C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd].C1(=CC=CC=C1)P(C1=CC=CC=C1)[C-]1C=CC=C1.[CH-]1C=CC=C1.[Fe+2].[Zn]
110
null
COc1cc2ncc(C#N)c(Nc3ccc(I)c4c3OCO4)c2cc1OC>C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.C=1C=CC(=CC1)/C=C/C(=O)/C=C/C2=CC=CC=C2.[Pd].[Pd].C1(=CC=CC=C1)P(C1=CC=CC=C1)[C-]1C=CC=C1.[CH-]1C=CC=C1.[Fe+2].[Zn]>COc1cc2ncc(C#N)c(Nc3ccc(C#N)c4c3OCO4)c2cc1OC
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-8b17765db61143fe8ca1338418d2ef04
CCO.Nc1cc(Cl)nc(N)n1>>CCOc1cc(N)nc(N)n1
[Na].ClC1=NC(=NC(=C1)N)N.C(C)O>>NC1=NC(=CC(=N1)OCC)N
[CH3:1][CH2:2][OH:3].Cl[c:4]1[cH:5][c:6]([NH2:7])[n:8][c:9]([NH2:10])[n:11]1>>[CH3:1][CH2:2][O:3][c:4]1[cH:5][c:6]([NH2:7])[n:8][c:9]([NH2:10])[n:11]1
CCO.Nc1cc(Cl)nc(N)n1
CCOc1cc(N)nc(N)n1
null
null
null
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
a445000eb5ed501274d93689ad5b9d45095af02deca02b6b541c8a834890a276
a4cafa7bcd156e21cca6eaac1b32e28ec8540642a31181122e6957f3d7559631
c1cncnc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](-[N;D1;H2:4]):[#7;a:5]:[c:6](-[N;D1;H2:7]):[c:8]:1.[C;D1;H3:9]-[C:10]-[OH;D1;+0:11]>>[C;D1;H3:9]-[C:10]-[O;H0;D2;+0:11]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3](-[N;D1;H2:4]):[#7;a:5]:[c:6](-[N;D1;H2:7]):[c:8]:1
72
[{"value": 72.0, "product": "NC1=NC(=CC(=N1)OCC)N", "details": "PERCENTYIELD", "is_desired": false}]
160
CELSIUS
null
null
To a solution of sodium (1.05 g) in ethanol (50 ml) was added 4-chloro-2,6-diaminopyrimidine (6 g, 41.4 mmoles). The resulting solution was heated in a reactor for 6 hours at 160° C. The reaction mixture was cooled down and the precipitated sodium chloride was filtered off. The filtrate was concentrated and precipitate...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary alcohol
Ether
c1cncnc1
c1cncnc1
c1cncnc1
HCl
null
160
null
CCO.Nc1cc(Cl)nc(N)n1>>CCOc1cc(N)nc(N)n1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-0e0e8be0a02f4c19bf09fd9226c5895a
CCOc1nc(N)nc(N)c1N=O>>CCOc1nc(N)nc(N)c1N
N(=O)C=1C(=NC(=NC1N)N)OCC.S(=O)([O-])S(=O)[O-].[Na+].[Na+].S(=O)([O-])S(=O)[O-].[Na+].[Na+]>>NC1=NC(=C(C(=N1)OCC)N)N
O=[N:12][c:11]1[c:4]([O:3][CH2:2][CH3:1])[n:5][c:6]([NH2:7])[n:8][c:9]1[NH2:10]>>[CH3:1][CH2:2][O:3][c:4]1[n:5][c:6]([NH2:7])[n:8][c:9]([NH2:10])[c:11]1[NH2:12]
CCOc1nc(N)nc(N)c1N=O
CCOc1nc(N)nc(N)c1N
null
null
O
Reduction
OtherReaction
10bd501bc4fc8c6849398545fc18bd5f6b51ea4e37b15a00157d17550a6b88bf
7085a0cec3cc6daaf2fab855d070c407558563b5b6837070687c0df0a552c6fe
c1cncnc1
O=[N;H0;D2;+0:1]-[c:2]1:[c:3](-[#8:4]):[#7;a:5]:[c:6]:[#7;a:7]:[c:8]:1-[N;D1;H2:9]>>[#8:4]-[c:3]1:[#7;a:5]:[c:6]:[#7;a:7]:[c:8](-[N;D1;H2:9]):[c:2]:1-[NH2;D1;+0:1]
61.1
[{"value": 61.0, "product": "NC1=NC(=C(C(=N1)OCC)N)N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 61.1, "product": "NC1=NC(=C(C(=N1)OCC)N)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
60
CELSIUS
4
HOUR
To a suspension of the compound of example 3 (7.12 g, 38.9 mmoles) in water (150 ml) at 60° C. was added sodium dithionite (46.7 mmol, 8.12 g). Additional sodium dithionite was added till the pink colour completely dis-appeared and a yellow solution was formed. The solution was stirred at 60° C. for another 4 hours. Wa...
10.6084/m9.figshare.5104873.v1
null
Nitroso
Primary amine
null
null
c1cncnc1
Other
O
60
4
CCOc1nc(N)nc(N)c1N=O>O>CCOc1nc(N)nc(N)c1N
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-ab953b8828c14caebd4e517da3330303
CCOc1nc(N)nc(N)c1N>>CCOc1nc(N)nc2nccnc12
NC1=NC(=C(C(=N1)OCC)N)N.C(=O)C=O>>NC1=NC2=NC=CN=C2C(=N1)OCC
[CH3:1][CH2:2][O:3][c:4]1[n:5][c:6]([NH2:7])[n:8][c:9]([NH2:10])[c:14]1[NH2:13]>>[CH3:1][CH2:2][O:3][c:4]1[n:5][c:6]([NH2:7])[n:8][c:9]2[n:10][cH:11][cH:12][n:13][c:14]12
CCOc1nc(N)nc(N)c1N
CCOc1nc(N)nc2nccnc12
null
null
C(C)O
Aromatic Heterocycle Formation
OtherReaction
fc8d78c77de84dd8af9389aacaf9f7ce807623ffdfe6a017dd3f1dcc98e11e6b
f6ca1788fc80057bd663c067fa50bcd2911a68a96991f331ace1350d4975ef8f
c1cnc2ncncc2n1
[#8:1]-[c:2]1:[#7;a:3]:[c:4]:[#7;a:5]:[c:6](-[NH2;D1;+0:7]):[c:8]:1-[NH2;D1;+0:9]>>[#8:1]-[c:2]1:[#7;a:3]:[c:4]:[#7;a:5]:[c:6]2:[n;H0;D2;+0:7]:[c:10]:[c:11]:[n;H0;D2;+0:9]:[c:8]:1:2
206.4
[{"value": 62.0, "product": "NC1=NC2=NC=CN=C2C(=N1)OCC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 206.4, "product": "NC1=NC2=NC=CN=C2C(=N1)OCC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
To a solution of 2,5,6-triamino-4-ethoxy-pyrimidine (10.54 g, 62.37 mmoles) in ethanol (160 ml) was added glyoxal (40% solution in water, 2.7 ml, 18.6 mmoles). The reaction mixture was refluxed for 4 hours. Some insoluble material was filtered off. The filtrate was concentrated in vacuo and the residue purified by flas...
10.6084/m9.figshare.5104873.v1
null
Primary amine.Primary amine
null
c1cncnc1
c1cnc2ncncc2n1
c1cnc2ncncc2n1
Other
C(C)O
null
null
CCOc1nc(N)nc(N)c1N>C(C)O>CCOc1nc(N)nc2nccnc12
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-a7163506c3194da89333aab8dff5b037
CCOc1nc(N)nc2nccnc12.OO>>CCOc1nc(N)nc2c1ncc[n+]2[O-]
NC1=NC2=NC=CN=C2C(=N1)OCC.OO.OO>>NC1=NC2=[N+](C=CN=C2C(=N1)OCC)[O-]
[CH3:1][CH2:2][O:3][c:4]1[n:5][c:6]([NH2:7])[n:8][c:9]2[c:10]1[n:11][cH:12][cH:13][n:14]2.O[OH:15]>>[CH3:1][CH2:2][O:3][c:4]1[n:5][c:6]([NH2:7])[n:8][c:9]2[c:10]1[n:11][cH:12][cH:13][n+:14]2[O-:15]
CCOc1nc(N)nc2nccnc12.OO
CCOc1nc(N)nc2c1ncc[n+]2[O-]
null
null
FC(C(=O)O)(F)F
Functional Group Interconversion
OtherReaction
108dc977992bfe7c24471cfde5d789d737cc08dd2f50746be656adc9ce41a01c
bf536f3bf8ed7b8faf08cf1c004ccd0a5e7fe59339402dd73ac837bb4a52f2ba
c1c[nH+]c2ncncc2n1
O-[OH;D1;+0:1].[#7;a:2]1:[c:3]:[c:4]:[n;H0;D2;+0:5]:[c:6]2:[#7;a:7]:[c:8]:[#7;a:9]:[c:10]:[c:11]:1:2>>[O-;H0;D1:1]-[n+;H0;D3:5]1:[c:4]:[c:3]:[#7;a:2]:[c:11]2:[c:10]:[#7;a:9]:[c:8]:[#7;a:7]:[c:6]:2:1
32
[{"value": 32.0, "product": "NC1=NC2=[N+](C=CN=C2C(=N1)OCC)[O-]", "details": "PERCENTYIELD", "is_desired": false}]
null
null
2
DAY
To a cooled (0° C.) solution of the compound of example 7 (2.47 g, 12.9 mmoles) in trifluoroacetic acid (53 ml) was added dropwise 2.53 ml of a 35% aqueous H2O2 solution. The reaction mixture was kept at 4° C. for two days in the refrigerator, whereby another 1.25 ml of the same H2O2 solution was added after 1 day. The...
10.6084/m9.figshare.5104873.v1
null
Peroxide
null
c1cnc2ncncc2n1
C1=Nc2cncnc2[NH+]=C1
C1=Nc2cncnc2[NH+]=C1
HO-
FC(C(=O)O)(F)F
null
48
CCOc1nc(N)nc2nccnc12.OO>FC(C(=O)O)(F)F>CCOc1nc(N)nc2c1ncc[n+]2[O-]
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3c88173537034105b7659e892ebb0d18
Nc1cc(O)nc(N)n1>>Nc1nc(N)c(N=O)c(O)n1
NC1=NC(=CC(=N1)O)N.C(C)(=O)O.N(=O)[O-].[Na+]>>NC1=NC(=C(C(=N1)O)N=O)N
[NH2:1][c:2]1[n:3][c:4]([NH2:5])[cH:6][c:9]([OH:10])[n:11]1>>[NH2:1][c:2]1[n:3][c:4]([NH2:5])[c:6]([N:7]=[O:8])[c:9]([OH:10])[n:11]1
Nc1cc(O)nc(N)n1
Nc1nc(N)c(N=O)c(O)n1
null
null
O
Functional Group Addition
OtherReaction
37b5dbf927322d4de54944b07579e1c735be607324387f2bb7b266fb591d966b
c852dfd7a307035d7b21dc79db1d13bba1cfffe7578c3caa265be3f4f0c038c5
c1cncnc1
[N;D1;H2:1]-[c:2]1:[#7;a:3]:[c:4]:[#7;a:5]:[c:6](-[O;D1;H1:7]):[cH;D2;+0:8]:1>>[N;D1;H2:1]-[c:2]1:[#7;a:3]:[c:4]:[#7;a:5]:[c:6](-[O;D1;H1:7]):[c;H0;D3;+0:8]:1-[#7:9]=[O;D1;H0:10]
97.3
[{"value": 97.0, "product": "NC1=NC(=C(C(=N1)O)N=O)N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 97.3, "product": "NC1=NC(=C(C(=N1)O)N=O)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
1
HOUR
To a solution of 2,6-diamino-4-hydroxypyrimidine (12.9 g, 102.2 mmoles) in 200 ml of a 10% acetic acid solution in water at 80° C. was added dropwise a solution of NaNO2 (7.05 g, 102.2 mmoles) in 20 ml water. A pink precipitate was formed, which was further stirred for 1 hour at 80° C. The reaction mixture was cooled d...
10.6084/m9.figshare.5104873.v1
null
null
Nitroso
c1cncnc1
c1cncnc1
c1cncnc1
Other
O
80
1
Nc1cc(O)nc(N)n1>O>Nc1nc(N)c(N=O)c(O)n1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-f987076083aa44828852f22275108aee
Nc1nc(N)c(N=O)c(O)n1>>Nc1nc(N)c(N)c(O)n1
NC1=NC(=C(C(=N1)O)N=O)N>>NC1=NC(=C(C(=N1)O)N)N
O=[N:7][c:6]1[c:4]([NH2:5])[n:3][c:2]([NH2:1])[n:10][c:8]1[OH:9]>>[NH2:1][c:2]1[n:3][c:4]([NH2:5])[c:6]([NH2:7])[c:8]([OH:9])[n:10]1
Nc1nc(N)c(N=O)c(O)n1
Nc1nc(N)c(N)c(O)n1
null
null
null
Reduction
OtherReaction
10bd501bc4fc8c6849398545fc18bd5f6b51ea4e37b15a00157d17550a6b88bf
7085a0cec3cc6daaf2fab855d070c407558563b5b6837070687c0df0a552c6fe
c1cncnc1
O=[N;H0;D2;+0:1]-[c:2]1:[c:3](-[N;D1;H2:4]):[#7;a:5]:[c:6]:[#7;a:7]:[c:8]:1-[O;D1;H1:9]>>[N;D1;H2:4]-[c:3]1:[#7;a:5]:[c:6]:[#7;a:7]:[c:8](-[O;D1;H1:9]):[c:2]:1-[NH2;D1;+0:1]
83
[{"value": 83.0, "product": "NC1=NC(=C(C(=N1)O)N)N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 83.0, "product": "NC1=NC(=C(C(=N1)O)N)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
50
CELSIUS
8
HOUR
A suspension of the compound of example 46 (15 g, 96.7 mmoles) in an ammonium sulfide solution (20% in water, 200 ml) was stirred overnight at 50° C. The reaction mixture was cooled down in the refrigerator and the precipitate was filtered off, providing the title compound as a yellow powder (11.33 g, yield: 83%). The ...
10.6084/m9.figshare.5104873.v1
null
Nitroso
Primary amine
null
null
c1cncnc1
Other
null
50
8
Nc1nc(N)c(N=O)c(O)n1>>Nc1nc(N)c(N)c(O)n1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-42095b2608ea4e5298f1660f83f003b0
CC(=O)OC(C)=O.COc1ccc(-c2cnc3c(n2)C(=O)NC(N)(N)N3)cc1OC>>COc1ccc(-c2cnc3c(n2)C(=O)NC(N)(NC(C)=O)N3)cc1OC
NC1(NC2=NC=C(N=C2C(N1)=O)C1=CC(=C(C=C1)OC)OC)N.C(C)(=O)OC(C)=O>>C(C)(=O)NC1(NC2=NC=C(N=C2C(N1)=O)C1=CC(=C(C=C1)OC)OC)N
CC(=O)O[C:19]([CH3:20])=[O:21].[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6](-[c:7]2[cH:8][n:9][c:10]3[c:11]([n:12]2)[C:13](=[O:14])[NH:15][C:16]([NH2:17])([NH2:18])[NH:22]3)[cH:23][c:24]1[O:25][CH3:26]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6](-[c:7]2[cH:8][n:9][c:10]3[c:11]([n:12]2)[C:13](=[O:14])[NH:15][C:16]([NH2:17])([NH:18][C:1...
CC(=O)OC(C)=O.COc1ccc(-c2cnc3c(n2)C(=O)NC(N)(N)N3)cc1OC
COc1ccc(-c2cnc3c(n2)C(=O)NC(N)(NC(C)=O)N3)cc1OC
null
null
C(C)(=O)O
Acylation
Aminolysis of esters
87d35e51b477fc9a658a6f307eb56d84c8879182772c9dd3a42ec0d584fd2684
627cbc0550c9f51ad0105d9fcf46677e8c93bed87ee95bfe69292a82550c95b7
O=C1NCNc2ncc(-c3ccccc3)nc21
C-C(=O)-O-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].[#7;a:4]:[c:5]1:[c:6](:[#7;a:7])-[#7:8]-[C:9](-[N;D1;H2:10])(-[NH2;D1;+0:11])-[#7:12]-[C:13]-1=[O;D1;H0:14]>>[#7;a:4]:[c:5]1:[c:6](:[#7;a:7])-[#7:8]-[C:9](-[N;D1;H2:10])(-[NH;D2;+0:11]-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3])-[#7:12]-[C:13]-1=[O;D1;H0:14]
77
[{"value": 77.0, "product": "C(C)(=O)NC1(NC2=NC=C(N=C2C(N1)=O)C1=CC(=C(C=C1)OC)OC)N", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
A suspension of the compound of example 48 (10.46 g, 35 mmoles) in acetic anhydride (600 ml) and acetic acid (200 ml) was refluxed for 1 hour until a clear solution was formed. By cooling down the reaction mixture in the refrigerator, the precipitate formed was filtered off, washed with ethyl acetate and diethyl ether,...
10.6084/m9.figshare.5104873.v1
null
Anhydride.Primary amine
Secondary amide
null
null
c1ccccc1.c1cnc2c(n1)CNCN2
HO-
C(C)(=O)O
null
null
CC(=O)OC(C)=O.COc1ccc(-c2cnc3c(n2)C(=O)NC(N)(N)N3)cc1OC>C(C)(=O)O>COc1ccc(-c2cnc3c(n2)C(=O)NC(N)(NC(C)=O)N3)cc1OC
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-fefcc001835f4ee6b6412f976a63b3b9
COc1ccc(-c2cnc3c(n2)C(=O)NC(N)(NC(C)=O)N3)cc1OC.c1nc[nH]n1>>COc1ccc(-c2cnc3nc(NC(C)=O)nc(-c4nc[nH]n4)c3n2)cc1OC
P(=O)(Cl)(Cl)Cl.N1N=CN=C1.C(C)(=O)NC1(NC2=NC=C(N=C2C(N1)=O)C1=CC(=C(C=C1)OC)OC)N>>C(C)(=O)NC1=NC2=NC=C(N=C2C(=N1)C1=NNC=N1)C1=CC(=C(C=C1)OC)OC
N[C:12]1([NH:13][C:14]([CH3:15])=[O:16])[NH:11][c:10]2[n:9][cH:8][c:7](-[c:6]3[cH:5][cH:4][c:3]([O:2][CH3:1])[c:27]([O:28][CH3:29])[cH:26]3)[n:25][c:24]2[C:18](=O)[NH:17]1.[cH:19]1[n:20][cH:21][nH:22][n:23]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6](-[c:7]2[cH:8][n:9][c:10]3[n:11][c:12]([NH:13][C:14]([CH3:15])=[O:16])[n:17]...
COc1ccc(-c2cnc3c(n2)C(=O)NC(N)(NC(C)=O)N3)cc1OC.c1nc[nH]n1
COc1ccc(-c2cnc3nc(NC(C)=O)nc(-c4nc[nH]n4)c3n2)cc1OC
null
null
N1=CC=CC=C1
C-C Coupling
OtherReaction
f1294a018bad143020ef05b115edad6e6dca734eacd2751311e9ec4df59cffcc
045628bbd55aa829413baf872876e233d703de880ade8dc61e36dec47c687179
c1ccc(-c2cnc3ncnc(-c4nc[nH]n4)c3n2)cc1
N-[C;H0;D4;+0:1]1(-[#7:2]-[C:3](-[C;D1;H3:4])=[O;D1;H0:5])-[NH;D2;+0:6]-[c:7]2:[#7;a:8]:[c:9]:[c:10]:[#7;a:11]:[c:12]:2-[C;H0;D3;+0:13](=O)-[NH;D2;+0:14]-1.[#7;a:15]1:[c:16]:[#7;a:17]:[#7;a:18]:[cH;D2;+0:19]:1>>[C;D1;H3:4]-[C:3](=[O;D1;H0:5])-[#7:2]-[c;H0;D3;+0:1]1:[n;H0;D2;+0:6]:[c:7]2:[#7;a:8]:[c:9]:[c:10]:[#7;a:11]:...
80
[{"value": 80.0, "product": "C(C)(=O)NC1=NC2=NC=C(N=C2C(=N1)C1=NNC=N1)C1=CC(=C(C=C1)OC)OC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 71.0, "product": "C(C)(=O)NC1=NC2=NC=C(N=C2C(=N1)C1=NNC=N1)C1=CC(=C(C=C1)OC)OC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
4
HOUR
To a solution of phosphorus oxychloride (1.68 ml, 18 mmoles) and 1,2,4-triazole (4.96 g, 72 mmoles) in dry pyridine (110 ml) was added the compound of example 49 (2.45 g, 7.18 mmoles). The suspension was stirred at room temperature for 4 hours. The precipitate was filtered off, washed with pyridine, toluene and diethyl...
10.6084/m9.figshare.5104873.v1
null
Secondary amide.Primary amine.Secondary amine
null
c1cnc2c(n1)CNCN2.c1nnc[nH]1
c1cnc2ncncc2n1.c1nnc[nH]1
c1ccccc1.c1cnc2ncncc2n1.c1nnc[nH]1
HO-
N1=CC=CC=C1
null
4
COc1ccc(-c2cnc3c(n2)C(=O)NC(N)(NC(C)=O)N3)cc1OC.c1nc[nH]n1>N1=CC=CC=C1>COc1ccc(-c2cnc3nc(NC(C)=O)nc(-c4nc[nH]n4)c3n2)cc1OC
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-0613de76870a471481a9a851d9c28680
CCOc1nc(N)nc2nc(-c3ccc(OC)c(OC)c3)cnc12>>COc1ccc(-c2cnc3c(OC)nc(N)nc3n2)cc1OC
COC=1C=C(C=CC1OC)C(=O)C=O.CO.NC1=NC2=NC(=CN=C2C(=N1)OCC)C1=CC(=C(C=C1)OC)OC>>NC1=NC2=NC(=CN=C2C(=N1)OC)C1=CC(=C(C=C1)OC)OC
C[CH2:13][O:12][c:11]1[c:10]2[n:9][cH:8][c:7](-[c:6]3[cH:5][cH:4][c:3]([O:2][CH3:1])[c:21]([O:22][CH3:23])[cH:20]3)[n:19][c:18]2[n:17][c:15]([NH2:16])[n:14]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6](-[c:7]2[cH:8][n:9][c:10]3[c:11]([O:12][CH3:13])[n:14][c:15]([NH2:16])[n:17][c:18]3[n:19]2)[cH:20][c:21]1[O:22][CH3:23]
CCOc1nc(N)nc2nc(-c3ccc(OC)c(OC)c3)cnc12
COc1ccc(-c2cnc3c(OC)nc(N)nc3n2)cc1OC
null
null
C(C)(C)O
Miscellaneous
OtherReaction
4aaa63d92793bb3347780900c7890c124a30137b2f711b41f0f3898a6907ad65
bced64702950df7cf56df22d8c2487b007734fece951727fd2c8a1c63fbcf6cc
c1ccc(-c2cnc3cncnc3n2)cc1
C-[CH2;D2;+0:1]-[#8:2]-[c:3](:[#7;a:4]):[c:5]:[#7;a:6]>>[#7;a:4]:[c:3](-[#8:2]-[CH3;D1;+0:1]):[c:5]:[#7;a:6]
null
[]
null
null
null
null
The sequence of reactions described in examples 53 to 57 was followed, however starting from 3,4-dimethoxyphenylglyoxal instead of 4-methoxyphenylglyoxal in the first step, and from methanol instead if isopropanol in the last step. This provided 2-amino-4-ethoxy-7-(3,4-dimethoxyphenyl) pteridine, a compound which was f...
10.6084/m9.figshare.5104873.v1
null
Ether
Ether
null
null
c1ccccc1.c1cnc2ncncc2n1
Other
C(C)(C)O
null
null
CCOc1nc(N)nc2nc(-c3ccc(OC)c(OC)c3)cnc12>C(C)(C)O>COc1ccc(-c2cnc3c(OC)nc(N)nc3n2)cc1OC
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9cac5a6be1a440569a97960ad86d737e
[Cl-].[Cl-]>>Cl.Cl
C1(=CC=CC=C1)C.S(=O)(=O)(O)O.CSC1=NC(=C(C(=N1)N)N)N.O.O.[Cl-].[Ba+2].[Cl-]>>Cl.Cl.NC1=NC(=NC(=C1N)N)SC
[Cl-:13].[Cl-:12]>>[ClH:12].[ClH:13]
[Cl-].[Cl-]
Cl.Cl
null
null
O
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
null
[Cl-;H0;D0:1].[Cl-;H0;D0:2]>>[ClH;D0;+0:2].[ClH;D0;+0:1]
209.9
[{"value": 94.0, "product": "Cl.Cl.NC1=NC(=NC(=C1N)N)SC", "details": "PERCENTYIELD", "is_desired": false}, {"value": 209.9, "product": "Cl.Cl.NC1=NC(=NC(=C1N)N)SC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
80
CELSIUS
30
MINUTE
To a suspension of a 2-methylmercapto-4,5,6-triamino-pyrimidine sulfate (44.3 mmole), which may be prepared and characterised for instance as disclosed by Taylor et al. in J. Am. Chem. Soc. (1952) 74:1644-1647, in water (135 ml) at 80° C. was added dropwise a solution of barium chloride dihydrate (39.8 mmole) in water ...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
null
null
O
80
0.5
[Cl-].[Cl-]>O>Cl.Cl
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-2a52eb2a457545149d25ef6aa9099ef1
C1COCCN1.Nc1cc(Cl)nc(N)n1>>Cl.Cl.Nc1nc(N)c(N)c(N2CCOCC2)n1
NC1=NC(=CC(=N1)Cl)N.[OH-].[Na+].N(=O)[O-].[Na+].C(C)(=O)O.[O-]S(=O)S(=O)[O-].[Na+].[Na+].N1CCOCC1>>Cl.Cl.NC1=NC(=C(C(=N1)N1CCOCC1)N)N
[NH:11]1[CH2:12][CH2:13][O:14][CH2:15][CH2:16]1.[Cl:1][c:10]1[n:5][c:6]([NH2:7])[n:17][c:4]([NH2:3])[cH:8]1>>[ClH:1].[ClH:2].[NH2:3][c:4]1[n:5][c:6]([NH2:7])[c:8]([NH2:9])[c:10]([N:11]2[CH2:12][CH2:13][O:14][CH2:15][CH2:16]2)[n:17]1
C1COCCN1.Nc1cc(Cl)nc(N)n1
Cl.Cl.Nc1nc(N)c(N)c(N2CCOCC2)n1
null
null
O
Functional Group Addition
OtherReaction
5d919bfd9fb985f9b74c387511f1e5e568f78dc5a39a9fa80c2ae2f1613e3a9f
e0c2fc0877589be5a2f60d823fe4ba547f59cb9f5f6884aee9c9c03b2aa675f7
c1cc(N2CCOCC2)ncn1
[#8:1]1-[C:2]-[C:3]-[NH;D2;+0:4]-[C:5]-[C:6]-1.[Cl;H0;D1;+0:7]-[c;H0;D3;+0:8]1:[cH;D2;+0:9]:[c;H0;D3;+0:10](-[N;D1;H2:11]):[n;H0;D2;+0:12]:[c;H0;D3;+0:13](-[N;D1;H2:14]):[n;H0;D2;+0:15]:1>>[ClH;D0;+0:7].[N;D1;H2:11]-[c;H0;D3;+0:10]1:[n;H0;D2;+0:12]:[c;H0;D3;+0:8](-[N;H0;D3;+0:4]2-[C:3]-[C:2]-[#8:1]-[C:6]-[C:5]-2):[c;H0...
141.3
[{"value": 54.1, "product": "Cl.Cl.NC1=NC(=C(C(=N1)N1CCOCC1)N)N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 141.3, "product": "Cl.Cl.NC1=NC(=C(C(=N1)N1CCOCC1)N)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
21
CELSIUS
null
null
In a 10 L 4-neck flask equipped with a mechanical stirrer, a thermometer and a heating mantle was placed 2,6-diamino-4-chloropyrimidine (870.5 g; 6.0 mol) In water (3190 ml). To the stirred resulting white suspension was added morpholine (1113 g; 12.8 moles) in one portion. The temperature raised from 14 to 28° C. and ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Secondary amine
Primary amine.Tertiary amine
C1COCCN1.c1cncnc1
c1cncnc1.C1COCC[NH]1
c1cncnc1.C1COCC[NH]1
Other
O
21
null
C1COCCN1.Nc1cc(Cl)nc(N)n1>O>Cl.Cl.Nc1nc(N)c(N)c(N2CCOCC2)n1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-186682100cc14e9eb9f5399f077666f1
COC(=O)C12CC3SC(C1)SC(C2)S3>>OCC12CC3SC(C1)SC(C2)S3
COC(=O)C12CC3SC(SC(C1)S3)C2.C1(=CC=CC=C1)C.[H-].C(C(C)C)[Al+]CC(C)C>>OCC12CC3SC(SC(C1)S3)C2
CO[C:2](=[O:1])[C:3]12[CH2:4][CH:5]3[S:6][CH:7]([CH2:8]1)[S:9][CH:10]([CH2:11]2)[S:12]3>>[OH:1][CH2:2][C:3]12[CH2:4][CH:5]3[S:6][CH:7]([CH2:8]1)[S:9][CH:10]([CH2:11]2)[S:12]3
COC(=O)C12CC3SC(C1)SC(C2)S3
OCC12CC3SC(C1)SC(C2)S3
null
null
CCCCCC
Reduction
Reduction of ester to primary alcohol
21d61543c6ec8a8cebe1b3ef55ef3dd20acbf79a4f1c12a7fb51e32be7a3248a
1fbcd628a0426673c5d10aa49a977cd2d1ae02a8cdf57bbb10d94aa03a94e937
C1C2CC3SC1SC(C2)S3
C-O-[C;H0;D3;+0:1](=[O;H0;D1;+0:2])-[C:3](-[C:4])(-[C:5])-[C:6]>>[C:4]-[C:3](-[CH2;D2;+0:1]-[OH;D1;+0:2])(-[C:5])-[C:6]
99
[{"value": 97.0, "product": "OCC12CC3SC(SC(C1)S3)C2", "details": "PERCENTYIELD", "is_desired": false}, {"value": 99.0, "product": "OCC12CC3SC(SC(C1)S3)C2", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
null
null
A flame-dried, 25 mL round-bottomed flask equipped with a Teflon-coated magnetic bar and a septum with an argon inlet was charged with 270 mg (1.10 mmol) of 2,4,9-Trithia-tricyclo[3.3.1.13,7]decane-7-carboxylic acid methyl ester and 5 mL of dry toluene. Cooled by an ice bath, the solution was charged with 1.60 mL of 1....
10.6084/m9.figshare.5104873.v1
null
Ester
Primary alcohol
null
null
C1C2CC3SC1SC(C2)S3
Other
CCCCCC
0
null
COC(=O)C12CC3SC(C1)SC(C2)S3>CCCCCC>OCC12CC3SC(C1)SC(C2)S3
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-6548c61644844463a0b82f95a1cc807e
COP(=O)(CC(C)=O)OC.CS(=O)(=O)N=[N+]=[N-]>>COP(=O)(OC)C(=[N+]=[N-])C(C)=O
[H-].[Na+].COP(OC)(=O)CC(C)=O.CS(=O)(=O)N=[N+]=[N-].CS(=O)(=O)Cl.[N-]=[N+]=[N-].[Na+]>>COP(OC)(=O)C(C(C)=O)=[N+]=[N-]
[CH3:1][O:2][P:3](=[O:4])([O:5][CH3:6])[CH2:7][C:10]([CH3:11])=[O:12].CS(=O)(=O)N=[N+:8]=[N-:9]>>[CH3:1][O:2][P:3](=[O:4])([O:5][CH3:6])[C:7](=[N+:8]=[N-:9])[C:10]([CH3:11])=[O:12]
COP(=O)(CC(C)=O)OC.CS(=O)(=O)N=[N+]=[N-]
COP(=O)(OC)C(=[N+]=[N-])C(C)=O
null
null
O1CCCC1.C1(=CC=CC=C1)C
Heteroatom Alkylation and Arylation
OtherReaction
f525e973623c74e01f3c5a05c7cc01f891477a2a97f7aa217686a22e249ae6e4
de0f460205316603b40264b68ab409d0fff8afb864d7a608428f60cbfbf83e35
null
C-S(=O)(=O)-N=[N+;H0;D2:1]=[N;-;D1;H0:2].[#8:3]-[#15:4](-[#8:5])(=[O;D1;H0:6])-[CH2;D2;+0:7]-[C:8](-[C;D1;H3:9])=[O;D1;H0:10]>>[#8:3]-[#15:4](-[#8:5])(=[O;D1;H0:6])-[C;H0;D3;+0:7](=[N+;H0;D2:1]=[N;-;D1;H0:2])-[C:8](-[C;D1;H3:9])=[O;D1;H0:10]
null
[]
null
null
1
HOUR
To an ice-cooled solution of sodium hydride in dry toluene, (2-oxo-propyl)-phosphonic acid dimethyl ester was added slowly. The solution mixture was stirred for 1 hour. Methanesulfonyl azide, prepared by the reaction of methanesulfonyl chloride and sodium azide, dissolved in dry toluene and dry tetrahydrofuran was adde...
10.6084/m9.figshare.5104873.v1
null
Ketone.Azide
Ketone.Diazo
null
null
null
HO-
O1CCCC1.C1(=CC=CC=C1)C
null
1
COP(=O)(CC(C)=O)OC.CS(=O)(=O)N=[N+]=[N-]>O1CCCC1.C1(=CC=CC=C1)C>COP(=O)(OC)C(=[N+]=[N-])C(C)=O
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9e724b691bf843049a0831ed12bdc474
C=C(CC(=O)O)C(=O)O.Nc1ccc(OCc2cccc(F)c2)cc1>>O=C(O)C1CC(=O)N(c2ccc(OCc3cccc(F)c3)cc2)C1
FC=1C=C(COC2=CC=C(C=C2)N)C=CC1.C(C(=C)CC(=O)O)(=O)O>>FC=1C=C(COC2=CC=C(C=C2)N2CC(CC2=O)C(=O)O)C=CC1
O[C:6]([CH2:5][C:4]([C:2](=[O:1])[OH:3])=[CH2:24])=[O:7].[NH2:8][c:9]1[cH:10][cH:11][c:12]([O:13][CH2:14][c:15]2[cH:16][cH:17][cH:18][c:19]([F:20])[cH:21]2)[cH:22][cH:23]1>>[O:1]=[C:2]([OH:3])[CH:4]1[CH2:5][C:6](=[O:7])[N:8]([c:9]2[cH:10][cH:11][c:12]([O:13][CH2:14][c:15]3[cH:16][cH:17][cH:18][c:19]([F:20])[cH:21]3)[cH...
C=C(CC(=O)O)C(=O)O.Nc1ccc(OCc2cccc(F)c2)cc1
O=C(O)C1CC(=O)N(c2ccc(OCc3cccc(F)c3)cc2)C1
null
null
C(C)(=O)O.C1(=CC=CC=C1)C
Protection
OtherReaction
37f4b8492750c7e46b0bee57601630c72bf8c7b6f749d4f241362f847080c4db
b19cad91dafaf954b8c8699d684122617f52c7d55786fc526451153a6a86c1ce
O=C1CCCN1c1ccc(OCc2ccccc2)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]-[C;H0;D3;+0:4](=[CH2;D1;+0:5])-[C:6](=[O;D1;H0:7])-[O;D1;H1:8].[NH2;D1;+0:9]-[c:10](:[c:11]):[c:12]>>[O;D1;H0:7]=[C:6](-[O;D1;H1:8])-[CH;D3;+0:4]1-[C:3]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[N;H0;D3;+0:9](-[c:10](:[c:11]):[c:12])-[CH2;D2;+0:5]-1
85.4
[{"value": 85.4, "product": "FC=1C=C(COC2=CC=C(C=C2)N2CC(CC2=O)C(=O)O)C=CC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
101
CELSIUS
3
HOUR
4-(3-Fluoro-benzyloxy)-phenylamine (31.2 g, 144 mmol) was dissolved in toluene (208 mL) and acetic acid (52 mL). Itaconic acid (18.96 g, 144 mmol) was added to the stirred mixture. The mixture was heated to reflux (101° C.) and kept at this temperature for 3 h. On cooling, the product started to crystallize. At 10° C.,...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine.Vinyl
Tertiary amide
null
C1CC[NH]C1
C1CC[NH]C1.c1ccccc1.c1ccccc1
HO-
C(C)(=O)O.C1(=CC=CC=C1)C
101
3
C=C(CC(=O)O)C(=O)O.Nc1ccc(OCc2cccc(F)c2)cc1>C(C)(=O)O.C1(=CC=CC=C1)C>O=C(O)C1CC(=O)N(c2ccc(OCc3cccc(F)c3)cc2)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-72c2bd1bad3a4eaf8405910a86c23279
O=C(O)C1CC(=O)N(c2ccc(OCc3cccc(F)c3)cc2)C1>>O=C(O)[C@H]1CC(=O)N(c2ccc(OCc3cccc(F)c3)cc2)C1
C1(=CC=CC=C1)[C@@H](N)CO.FC=1C=C(COC2=CC=C(C=C2)N2CC(CC2=O)C(=O)O)C=CC1.C1(=CC=CC=C1)[C@@H](N)CO>>FC=1C=C(COC2=CC=C(C=C2)N2C[C@H](CC2=O)C(=O)O)C=CC1
[O:1]=[C:2]([OH:3])[CH:4]1[CH2:5][C:6](=[O:7])[N:8]([c:9]2[cH:10][cH:11][c:12]([O:13][CH2:14][c:15]3[cH:16][cH:17][cH:18][c:19]([F:20])[cH:21]3)[cH:22][cH:23]2)[CH2:24]1>>[O:1]=[C:2]([OH:3])[C@H:4]1[CH2:5][C:6](=[O:7])[N:8]([c:9]2[cH:10][cH:11][c:12]([O:13][CH2:14][c:15]3[cH:16][cH:17][cH:18][c:19]([F:20])[cH:21]3)[cH:...
O=C(O)C1CC(=O)N(c2ccc(OCc3cccc(F)c3)cc2)C1
O=C(O)[C@H]1CC(=O)N(c2ccc(OCc3cccc(F)c3)cc2)C1
null
null
C(C)#N.O
Miscellaneous
OtherReaction
40ba59785861b8226ce5af6bdcbb9a37f0ff50a8c7ec7d4fc4c524cf906cc65c
56ebed4a8b3cebec83c37a71d68f0c87d1e404ab05a9ce792691e4e18a2379dd
O=C1CCCN1c1ccc(OCc2ccccc2)cc1
null
44.1
[{"value": 44.0, "product": "FC=1C=C(COC2=CC=C(C=C2)N2C[C@H](CC2=O)C(=O)O)C=CC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 44.1, "product": "FC=1C=C(COC2=CC=C(C=C2)N2C[C@H](CC2=O)C(=O)O)C=CC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
The salt of the (S)-(II) compound with (R)-(−)-2-phenylglycinol was prepared in an analogous manner as described in Example 2a) from rac-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid (5 g, 15.2 mmol) in acetonitrile/water 95:5 (50 mL) using a solution of only 1.46 g (R)-(−)-2-phenylglycinol (10....
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
C1CC[NH]C1.c1ccccc1.c1ccccc1
null
C(C)#N.O
null
null
O=C(O)C1CC(=O)N(c2ccc(OCc3cccc(F)c3)cc2)C1>C(C)#N.O>O=C(O)[C@H]1CC(=O)N(c2ccc(OCc3cccc(F)c3)cc2)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-3274c4ad445b487685d712c5420123db
O=C(O)[C@H]1CC(=O)N(c2ccc(OCc3cccc(F)c3)cc2)C1>>NC(=O)[C@H]1CC(=O)N(c2ccc(OCc3cccc(F)c3)cc2)C1
C(=O)(N1C=NC=C1)N1C=NC=C1.FC=1C=C(COC2=CC=C(C=C2)N2C[C@H](CC2=O)C(=O)O)C=CC1>>FC=1C=C(COC2=CC=C(C=C2)N2C[C@H](CC2=O)C(=O)N)C=CC1
O[C:2](=[O:3])[C@H:4]1[CH2:5][C:6](=[O:7])[N:8]([c:9]2[cH:10][cH:11][c:12]([O:13][CH2:14][c:15]3[cH:16][cH:17][cH:18][c:19]([F:20])[cH:21]3)[cH:22][cH:23]2)[CH2:24]1>>[NH2:1][C:2](=[O:3])[C@H:4]1[CH2:5][C:6](=[O:7])[N:8]([c:9]2[cH:10][cH:11][c:12]([O:13][CH2:14][c:15]3[cH:16][cH:17][cH:18][c:19]([F:20])[cH:21]3)[cH:22]...
O=C(O)[C@H]1CC(=O)N(c2ccc(OCc3cccc(F)c3)cc2)C1
NC(=O)[C@H]1CC(=O)N(c2ccc(OCc3cccc(F)c3)cc2)C1
null
null
O1CCCC1
Functional Group Interconversion
OtherReaction
e1b1a1f71ee10336b9e90a021457b106dbfe08a22161aaad6804675a8134a46f
5d384be3554a01fd49be5eb779c3b10075a4cc9a2373eb20aaa867286d4e28a9
O=C1CCCN1c1ccc(OCc2ccccc2)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]1-[C:4]-[#7:5]-[C:6](=[O;D1;H0:7])-[C:8]-1>>[N;D1;H2:9]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]1-[C:4]-[#7:5]-[C:6](=[O;D1;H0:7])-[C:8]-1
96.7
[{"value": 96.0, "product": "FC=1C=C(COC2=CC=C(C=C2)N2C[C@H](CC2=O)C(=O)N)C=CC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 96.7, "product": "FC=1C=C(COC2=CC=C(C=C2)N2C[C@H](CC2=O)C(=O)N)C=CC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
18
CELSIUS
15
MINUTE
1,1′-carbonyldiimidazole (8.27 g, 51.0 mmol) was suspended and partly dissolved in tetrahydrofuran (110 mL) at 18° C. (S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid (14.0 g, 42.5 mmol; enantiomeric purity (S):(R)=99.5:0.5) was added as a solid together with tetrahydrofuran (30 mL) used for ri...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid
Primary amide
null
null
C1CC[NH]C1.c1ccccc1.c1ccccc1
null
O1CCCC1
18
0.25
O=C(O)[C@H]1CC(=O)N(c2ccc(OCc3cccc(F)c3)cc2)C1>O1CCCC1>NC(=O)[C@H]1CC(=O)N(c2ccc(OCc3cccc(F)c3)cc2)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-99a3cd4705164cea8d3bb8067b7d2d30
O=C(O)[C@H]1CC(=O)N(c2ccc(OCc3cccc(F)c3)cc2)C1>>NC(=O)[C@H]1CC(=O)N(c2ccc(OCc3cccc(F)c3)cc2)C1
ClC(=O)OCC.FC=1C=C(COC2=CC=C(C=C2)N2C[C@H](CC2=O)C(=O)O)C=CC1.CN1CCOCC1>>FC=1C=C(COC2=CC=C(C=C2)N2C[C@H](CC2=O)C(=O)N)C=CC1
O[C:2](=[O:3])[C@H:4]1[CH2:5][C:6](=[O:7])[N:8]([c:9]2[cH:10][cH:11][c:12]([O:13][CH2:14][c:15]3[cH:16][cH:17][cH:18][c:19]([F:20])[cH:21]3)[cH:22][cH:23]2)[CH2:24]1>>[NH2:1][C:2](=[O:3])[C@H:4]1[CH2:5][C:6](=[O:7])[N:8]([c:9]2[cH:10][cH:11][c:12]([O:13][CH2:14][c:15]3[cH:16][cH:17][cH:18][c:19]([F:20])[cH:21]3)[cH:22]...
O=C(O)[C@H]1CC(=O)N(c2ccc(OCc3cccc(F)c3)cc2)C1
NC(=O)[C@H]1CC(=O)N(c2ccc(OCc3cccc(F)c3)cc2)C1
null
null
O1CCCC1
Functional Group Interconversion
OtherReaction
e1b1a1f71ee10336b9e90a021457b106dbfe08a22161aaad6804675a8134a46f
5d384be3554a01fd49be5eb779c3b10075a4cc9a2373eb20aaa867286d4e28a9
O=C1CCCN1c1ccc(OCc2ccccc2)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]1-[C:4]-[#7:5]-[C:6](=[O;D1;H0:7])-[C:8]-1>>[N;D1;H2:9]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[C:3]1-[C:4]-[#7:5]-[C:6](=[O;D1;H0:7])-[C:8]-1
88
[{"value": 88.0, "product": "FC=1C=C(COC2=CC=C(C=C2)N2C[C@H](CC2=O)C(=O)N)C=CC1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 87.8, "product": "FC=1C=C(COC2=CC=C(C=C2)N2C[C@H](CC2=O)C(=O)N)C=CC1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
20
MINUTE
To (S)-1-[4-(3-fluoro-benzyloxy)-phenyl]-5-oxo-pyrrolidine-3-carboxylic acid (2.0 g, 6.07 mmol; enantiomeric purity (S):(R)>99.9:0.1) in tetrahydrofuran (40 mL), N-methylmor-pholine (676 mg, 6.68 mmol) was added at 0° C. After stirring for 20 min, a solution of ethyl chloroformate (725 mg, 6.68 mmol) was added dropwise...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid
Primary amide
null
null
C1CC[NH]C1.c1ccccc1.c1ccccc1
null
O1CCCC1
null
0.333333
O=C(O)[C@H]1CC(=O)N(c2ccc(OCc3cccc(F)c3)cc2)C1>O1CCCC1>NC(=O)[C@H]1CC(=O)N(c2ccc(OCc3cccc(F)c3)cc2)C1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9d5f7e23615a49bb80c50ab907f1f4fa
CC(C)=CC(C)CCCCC=O>>CC(C)=CC(C)CCCCCO
[BH4-].[Na+].CC(CCCCC=O)C=C(C)C.CC(=O)C>>CC(CCCCCO)C=C(C)C
[CH3:1][C:2]([CH3:3])=[CH:4][CH:5]([CH3:6])[CH2:7][CH2:8][CH2:9][CH2:10][CH:11]=[O:12]>>[CH3:1][C:2]([CH3:3])=[CH:4][CH:5]([CH3:6])[CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][OH:12]
CC(C)=CC(C)CCCCC=O
CC(C)=CC(C)CCCCCO
null
null
C(C)O
Reduction
Reduction of aldehydes and ketones to alcohols
e7895795cd3f75445716c94697823c5929dcd4b5344525875fe75d36bca2f9d7
21bb81d5469aaaca71ab12c186bea4016451717fad8780cf288858a7d8fbc55a
null
[C:1]-[C:2]-[CH;D2;+0:3]=[O;H0;D1;+0:4]>>[C:1]-[C:2]-[CH2;D2;+0:3]-[OH;D1;+0:4]
72.7
[{"value": 72.7, "product": "CC(CCCCCO)C=C(C)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
16
HOUR
18 g (0.11 mol) of 6,8-dimethylnon-7-enal (1) and 96.0 g of ethanol are placed in a 500 ml round-bottomed flask equipped with a thermometer. Cooling is carried out to 5° C. and 2.0 g of sodium borohydride are added in small portions without exceeding a bulk temperature of 10° C. The mixture is stirred at ambient temper...
10.6084/m9.figshare.5104873.v1
null
Aldehyde
Primary alcohol
null
null
null
null
C(C)O
null
16
CC(C)=CC(C)CCCCC=O>C(C)O>CC(C)=CC(C)CCCCCO
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-8a0cfead0535481bb11cf20b7fe8c21b
CC(=O)Cl.CC(C)=CC(C)CCCCCO>>CC(=O)OCCCCCC(C)C=C(C)C
Cl.C(C)(=O)Cl.CC(CCCCCO)C=C(C)C.C(C)N(CC)CC>>C(C)(=O)OCCCCCC(C=C(C)C)C
Cl[C:2]([CH3:1])=[O:3].[OH:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]([CH3:11])[CH:12]=[C:13]([CH3:14])[CH3:15]>>[CH3:1][C:2](=[O:3])[O:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH:10]([CH3:11])[CH:12]=[C:13]([CH3:14])[CH3:15]
CC(=O)Cl.CC(C)=CC(C)CCCCCO
CC(=O)OCCCCCC(C)C=C(C)C
null
null
CC(C)(C)OC.COC(C)(C)C
Acylation
Schotten-Baumann to ester
6cefe709828c5bd4655f254e75d5dff9e8876e192e7dd47256c1bc0067bc5291
d8a7643b81ed07a6f633aa99465180dfa0565e61ae25aef36338ebb9837c9cef
null
Cl-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3].[C:4]-[C:5]-[OH;D1;+0:6]>>[C:4]-[C:5]-[O;H0;D2;+0:6]-[C;H0;D3;+0:1](-[C;D1;H3:2])=[O;D1;H0:3]
76
[{"value": 76.0, "product": "C(C)(=O)OCCCCCC(C=C(C)C)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
14
HOUR
13 g (76 mmol) of 6,8-dimethylnon-7-enol (2), 10.8 g (107 mmol) of triethylamine and 200 ml of t-butyl methyl ether (MTBE) are placed in a 500 ml round-bottomed flask equipped with a thermometer and with a dropping funnel. Cooling is carried out to 5° C. and 8.4 g (107 mmol) of acetylchloride diluted in 20 ml of MTBE a...
10.6084/m9.figshare.5104873.v1
null
Acyl halide.Primary alcohol
Ester
null
null
null
HCl
CC(C)(C)OC.COC(C)(C)C
null
14
CC(=O)Cl.CC(C)=CC(C)CCCCCO>CC(C)(C)OC.COC(C)(C)C>CC(=O)OCCCCCC(C)C=C(C)C
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-9f255ad1273e447f8231f3257934c590
C1=Cc2cc3ccc(cc4nc(cc5ccc(cc1n2)[nH]5)C=C4)[nH]3.O.O=C(O)C(F)(F)F>>O=Cc1c2nc(cc3ccc([nH]3)c(C=O)c3nc(cc4ccc1[nH]4)C=C3)C=C2
C(Cl)Cl.C(=O)(C(F)(F)F)O.O.C12=CC=C(N1)C=C1C=CC(=N1)C=C1C=CC(N1)=CC=1C=CC(N1)=C2>>C(=O)C=1C2=CC=C(N2)C=C2C=CC(C(=C3C=CC(=CC=4C=CC1N4)N3)C=O)=N2
[cH:3]1[c:4]2[n:12][c:11]([cH:13][c:8]3[nH:5][c:6]([cH:7][c:16]4[n:17][c:18]([cH:19][c:20]5[cH:21][cH:22][c:23]1[nH:24]5)[CH:25]=[CH:26]4)[cH:27][cH:9]3)[CH:14]=[CH:28]2.[OH2:15].O[C:2](C(F)(F)F)=[O:1]>>[O:1]=[CH:2][c:3]1[c:4]2[n:5][c:6]([cH:7][c:8]3[cH:9][cH:10][c:11]([nH:12]3)[c:13]([CH:14]=[O:15])[c:16]3[n:17][c:18]...
C1=Cc2cc3ccc(cc4nc(cc5ccc(cc1n2)[nH]5)C=C4)[nH]3.O.O=C(O)C(F)(F)F
O=Cc1c2nc(cc3ccc([nH]3)c(C=O)c3nc(cc4ccc1[nH]4)C=C3)C=C2
null
null
null
C-C Coupling
OtherReaction
443dd67cc9c01ed0795d185a67926577b0f416fb123913db5536a50fb92d4b8f
7da96aa513b345413c024fd57b4b61b8e16a6aa46bc791df63a30112399db1fc
C1=Cc2cc3ccc(cc4nc(cc5ccc(cc1n2)[nH]5)C=C4)[nH]3
F-C(-F)(-F)-[C;H0;D3;+0:1](-O)=[O;D1;H0:2].[OH2;D0;+0:3].[c:4]:[#7;a:5]:[c:6](:[c:7]):[cH;D2;+0:8]:[c;H0;D3;+0:9]1:[n;H0;D2;+0:10]:[c;H0;D3;+0:11](:[cH;D2;+0:12]:[c;H0;D3;+0:13]2:[cH;D2;+0:14]:[cH;D2;+0:15]:[c:16](:[cH;D2;+0:17]:[c;H0;D3;+0:18]3:[#7;a:19]:[c:20]-[C:21]=[C:22]-3):[nH;D2;+0:23]:2)-[CH;D2;+0:24]=[CH;D2;+0...
90
[{"value": 90.0, "product": "C(=O)C=1C2=CC=C(N2)C=C2C=CC(C(=C3C=CC(=CC=4C=CC1N4)N3)C=O)=N2", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The route that employs a dipyrromethane-monocarbinol bearing the acetal at the 5-position begins with dipyrromethane 2. Treatment of 2 under the standard conditions for 1-acylation16 with pyridyl thioester 6 afforded the 1-acyldipyrromethane 7 in 72% yield. Reduction of 7 with NaBH4 and self-condensation16,21 of the re...
10.6084/m9.figshare.5104873.v1
null
Trifluoro group.Carboxylic acid
Aldehyde.Aldehyde
C1=Cc2cc3ccc(cc4nc(cc5ccc(cc1n2)n5)C=C4)n3
C1=Cc2cc3ccc(cc4nc(cc5ccc(cc1n2)n5)C=C4)n3
C1=Cc2cc3ccc(cc4nc(cc5ccc(cc1n2)n5)C=C4)n3
HF
null
null
null
C1=Cc2cc3ccc(cc4nc(cc5ccc(cc1n2)[nH]5)C=C4)[nH]3.O.O=C(O)C(F)(F)F>>O=Cc1c2nc(cc3ccc([nH]3)c(C=O)c3nc(cc4ccc1[nH]4)C=C3)C=C2
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-4a1c97c9bb4c4b699f0f6ce0d76f9695
CC(C)(CO)CO.O=CC=O>>CC1(C)COC(C=O)OC1
[O-]S(=O)(=O)[O-].[Na+].[Na+].C(=O)C=O.CC(CO)(CO)C.C1(=CC=C(C=C1)S(=O)(=O)O)C.C(=O)(O)[O-].[Na+]>>C(=O)C1OCC(CO1)(C)C
O[CH2:10][C:2]([CH3:1])([CH3:3])[CH2:4][OH:5].[CH:6]([CH:7]=[O:8])=[O:9]>>[CH3:1][C:2]1([CH3:3])[CH2:4][O:5][CH:6]([CH:7]=[O:8])[O:9][CH2:10]1
CC(C)(CO)CO.O=CC=O
CC1(C)COC(C=O)OC1
null
null
C1=CC=CC=C1
Heteroatom Alkylation and Arylation
OtherReaction
73c19e1dd216070b15ec212a551c866306f9ce0633eef38c38086c49c4ffca15
84f906b915b11ab21e1cc1ae9ab26ccac04fa933222d2c0dda259055bdf62145
C1COCOC1
O-[CH2;D2;+0:1]-[C:2](-[C;D1;H3:3])(-[C;D1;H3:4])-[C:5]-[OH;D1;+0:6].[O;D1;H0:7]=[C:8]-[CH;D2;+0:9]=[O;H0;D1;+0:10]>>[C;D1;H3:3]-[C:2]1(-[C;D1;H3:4])-[C:5]-[O;H0;D2;+0:6]-[CH;D3;+0:9](-[C:8]=[O;D1;H0:7])-[O;H0;D2;+0:10]-[CH2;D2;+0:1]-1
4.1
[{"value": 4.0, "product": "C(=O)C1OCC(CO1)(C)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 4.1, "product": "C(=O)C1OCC(CO1)(C)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
A mixture of glyoxal (10.0 g of 40 wt. % aqueous solution, 0.070 mol), 2,2-dimethyl-1,3-propanediol (7.28 g, 0.070 mol) and p-toluenesulfonic acid (0.260 g, 1.36 mmol) in benzene (140 mL) was refluxed for 4 h in a flask fitted with a Soxhlet extractor containing Na2SO4. Then the reaction mixture was treated with solid ...
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Aldehyde.Primary alcohol.Primary alcohol
Aldehyde.Ether.Ether
null
C1COCOC1
C1COCOC1
HO-
C1=CC=CC=C1
null
null
CC(C)(CO)CO.O=CC=O>C1=CC=CC=C1>CC1(C)COC(C=O)OC1
ord_dataset-c31cb9b44c404c10ba3aa533aa079e2b
ord-d72dde9035f24cf9900e94d149553176
CC(C)(CO)CO.O=CC=O>>CC1(C)COC(C=O)OC1
C(=O)C=O.CC(CO)(CO)C.C1(=CC=C(C=C1)S(=O)(=O)O)C.C(=O)(O)[O-].[Na+].[O-]S(=O)(=O)[O-].[Na+].[Na+]>>C(=O)C1OCC(CO1)(C)C
O[CH2:10][C:2]([CH3:1])([CH3:3])[CH2:4][OH:5].[CH:6]([CH:7]=[O:8])=[O:9]>>[CH3:1][C:2]1([CH3:3])[CH2:4][O:5][CH:6]([CH:7]=[O:8])[O:9][CH2:10]1
CC(C)(CO)CO.O=CC=O
CC1(C)COC(C=O)OC1
null
null
C1=CC=CC=C1
Heteroatom Alkylation and Arylation
OtherReaction
73c19e1dd216070b15ec212a551c866306f9ce0633eef38c38086c49c4ffca15
84f906b915b11ab21e1cc1ae9ab26ccac04fa933222d2c0dda259055bdf62145
C1COCOC1
O-[CH2;D2;+0:1]-[C:2](-[C;D1;H3:3])(-[C;D1;H3:4])-[C:5]-[OH;D1;+0:6].[O;D1;H0:7]=[C:8]-[CH;D2;+0:9]=[O;H0;D1;+0:10]>>[C;D1;H3:3]-[C:2]1(-[C;D1;H3:4])-[C:5]-[O;H0;D2;+0:6]-[CH;D3;+0:9](-[C:8]=[O;D1;H0:7])-[O;H0;D2;+0:10]-[CH2;D2;+0:1]-1
50
[{"value": 50.0, "product": "C(=O)C1OCC(CO1)(C)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Streamlined Synthesis of 5-(5,5-Dimethyl-1,3-dioxan-2-yl)dipyrromethane (2). A mixture of glyoxal (10.0 g of 40 wt. % aqueous solution, 0.070 mol), 2,2-dimethyl 1,3-propanediol (7.28 g, 0.070 mol) and p-toluenesulfonic acid (0.260 g, 1.36 mmol) in benzene (140 mL) was refluxed for 4 h in a flask fitted with a Soxhlet e...
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Aldehyde.Primary alcohol.Primary alcohol
Aldehyde.Ether.Ether
null
C1COCOC1
C1COCOC1
HO-
C1=CC=CC=C1
null
null
CC(C)(CO)CO.O=CC=O>C1=CC=CC=C1>CC1(C)COC(C=O)OC1