dataset_id
large_stringclasses
414 values
reaction_id
large_stringlengths
36
36
reaction_smiles
large_stringlengths
4
873
rxn_insight_reaction
large_stringlengths
19
1.07k
mapped_reaction_smiles
large_stringlengths
14
3.37k
reactant_smiles
large_stringlengths
1
581
product_smiles
large_stringlengths
1
433
reagent_smiles
large_stringclasses
634 values
catalyst_smiles
large_stringlengths
1
683
solvent_smiles
large_stringlengths
1
245
rxn_insight_class
large_stringclasses
11 values
rxn_insight_name
large_stringclasses
346 values
rxn_insight_tag
large_stringlengths
64
64
rxn_insight_tag2
large_stringlengths
64
64
rxn_insight_scaffold
large_stringlengths
5
288
rxn_insight_template
large_stringlengths
24
2.64k
yield_percent
float64
-0.8
90,205,160,000B
yield_measurements
large_stringlengths
2
864
temperature_value
float64
-230
30.1k
temperature_units
large_stringclasses
3 values
reaction_time_value
float64
0
4k
time_units
large_stringclasses
4 values
procedure_details
large_stringlengths
1
23.6k
reference
large_stringclasses
96 values
doi
large_stringclasses
19 values
functional_groups_reactants
large_stringlengths
3
716
functional_groups_products
large_stringlengths
3
539
participating_rings_reactants
large_stringlengths
5
293
participating_rings_products
large_stringlengths
5
271
all_rings_products
large_stringlengths
5
271
byproduct_smiles
large_stringclasses
176 values
agent_smiles
large_stringlengths
1
712
temperature_c
float64
-230
30.1k
reaction_time_hours
float64
0
2.16k
reaction_smiles_with_agents
large_stringlengths
4
882
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-1e238da9ec0441dc8fe8397dcb8c5375
C#Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1>>CCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)C#C)F>>C(C)C1=CC(=C(C=C1)NC1=C(C(=O)O)C=CC(=C1F)F)F
[CH:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([NH:7][c:8]2[c:9]([C:10](=[O:11])[OH:12])[cH:13][cH:14][c:15]([F:16])[c:17]2[F:18])[c:19]([F:20])[cH:21]1>>[CH3:1][CH2:2][c:3]1[cH:4][cH:5][c:6]([NH:7][c:8]2[c:9]([C:10](=[O:11])[OH:12])[cH:13][cH:14][c:15]([F:16])[c:17]2[F:18])[c:19]([F:20])[cH:21]1
C#Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
CCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
null
[Pd]
C(C)O
Reduction
OtherReaction
2bb8d5b532a2781e0a7c069a5cd3e8a7e8d44660c0ec1d9e17c04d8ba2cb383b
1990560e9c55934bde8ca0feaed9c61d80f37f94f0cf240a9929dc374d0a33aa
c1ccc(Nc2ccccc2)cc1
[CH;D1;+0:1]#[C;H0;D2;+0:2]-[c:3](:[c:4]):[c:5]>>[CH3;D1;+0:1]-[CH2;D2;+0:2]-[c:3](:[c:4]):[c:5]
92.1
[{"value": 92.0, "product": "C(C)C1=CC(=C(C=C1)NC1=C(C(=O)O)C=CC(=C1F)F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 92.1, "product": "C(C)C1=CC(=C(C=C1)NC1=C(C(=O)O)C=CC(=C1F)F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
The product of Step C, 3,4-difluoro-2-[(4-ethynyl-2-fluorophenyl)amino]benzoic acid (300 mg, 1.03 mmol), was dissolved in absolute ethanol (30 mL) and 5% Pd/C (30 mg) added. This mixture was stirred under an atmosphere of hydrogen (60 psi) for 2 hours at room temperature. The Pd/C was removed over Celite®, which was wa...
10.6084/m9.figshare.5104873.v1
null
Alkyne
null
null
null
c1ccccc1.c1ccccc1
null
[Pd].C(C)O
null
2
C#Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1>[Pd].C(C)O>CCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-4ecc0f5765204fb38ea527400b4d8bc4
CCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO>>CCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
[N-]1C=NC=C1.NOCCO.C(C)C1=CC(=C(C=C1)NC1=C(C(=O)O)C=CC(=C1F)F)F.C(=O)(N1C=NC=C1)N1C=NC=C1>>C(C)C1=CC(=C(C=C1)NC1=C(C(=O)NOCCO)C=CC(=C1F)F)F
O[C:10]([c:9]1[c:8]([NH:7][c:6]2[cH:5][cH:4][c:3]([CH2:2][CH3:1])[cH:25][c:23]2[F:24])[c:21]([F:22])[c:19]([F:20])[cH:18][cH:17]1)=[O:11].[NH2:12][O:13][CH2:14][CH2:15][OH:16]>>[CH3:1][CH2:2][c:3]1[cH:4][cH:5][c:6]([NH:7][c:8]2[c:9]([C:10](=[O:11])[NH:12][O:13][CH2:14][CH2:15][OH:16])[cH:17][cH:18][c:19]([F:20])[c:21]2...
CCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO
CCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
null
null
C1CCOC1
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
c1ccc(Nc2ccccc2)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C:6]-[#8:7]-[NH2;D1;+0:8]>>[C:6]-[#8:7]-[NH;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
65
[{"value": 65.0, "product": "C(C)C1=CC(=C(C=C1)NC1=C(C(=O)NOCCO)C=CC(=C1F)F)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
10
MINUTE
The title compound was prepared from the reaction of the product of Step D, 2-[(4-ethyl-2-fluorophenyl)amino]-3,4-difluorobenzoic acid (93 mg, 0.32 mmol) dissolved in dry THF (5 mL), and carbonyldiimidazole (CDI) (102 mg, 0.63 mmol). Within 10 minutes, a bright yellow solution was obtained and conversion to the imidazo...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccccc1.c1ccccc1
HO-
C1CCOC1
null
0.166667
CCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO>C1CCOC1>CCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-899d1d4e9b5d4a96af3a362160180f80
O=C(O)c1ccc(F)c(F)c1Nc1ccc(I)cc1Cl.O=C(Oc1c(F)c(F)c(F)c(F)c1F)C(F)(F)F>>O=C(Oc1c(F)c(F)c(F)c(F)c1F)c1ccc(F)c(F)c1Nc1ccc(I)cc1Cl
ClC1=C(C=CC(=C1)I)NC1=C(C(=O)O)C=CC(=C1F)F.ClC1=C(C=CC(=C1)I)NC1=C(C(=O)O)C=CC(=C1F)F.N1=CC=CC=C1.FC(C(=O)OC1=C(C(=C(C(=C1F)F)F)F)F)(F)F>>FC1=C(C(=C(C(=C1OC(C1=C(C(=C(C=C1)F)F)NC1=C(C=C(C=C1)I)Cl)=O)F)F)F)F
O=C(O)[c:15]1[cH:16][cH:17][c:18]([F:19])[c:20]([F:21])[c:22]1[NH:23][c:24]1[cH:25][cH:26][c:27]([I:28])[cH:29][c:30]1[Cl:31].FC(F)(F)[C:2](=[O:1])[O:3][c:4]1[c:5]([F:6])[c:7]([F:8])[c:9]([F:10])[c:11]([F:12])[c:13]1[F:14]>>[O:1]=[C:2]([O:3][c:4]1[c:5]([F:6])[c:7]([F:8])[c:9]([F:10])[c:11]([F:12])[c:13]1[F:14])[c:15]1[...
O=C(O)c1ccc(F)c(F)c1Nc1ccc(I)cc1Cl.O=C(Oc1c(F)c(F)c(F)c(F)c1F)C(F)(F)F
O=C(Oc1c(F)c(F)c(F)c(F)c1F)c1ccc(F)c(F)c1Nc1ccc(I)cc1Cl
null
null
CN(C=O)C.C(C)(=O)OCC
C-C Coupling
OtherReaction
a107b7fa240a00727def35d9f3f3d79f77e3bfda9f2cc9627f9211a6797e9acc
c8a900bd957c46e0c8e28722dfe9262f44e12b24af7a12a545c112943e69a54a
O=C(Oc1ccccc1)c1ccccc1Nc1ccccc1
F-C(-F)(-F)-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[c:4].O-C(=O)-[c;H0;D3;+0:5](:[c:6]:[c:7]):[c:8](-[#7:9]):[c:10]>>[#7:9]-[c:8](:[c:10]):[c;H0;D3;+0:5](-[C;H0;D3;+0:1](=[O;D1;H0:2])-[#8:3]-[c:4]):[c:6]:[c:7]
91
[{"value": 91.0, "product": "FC1=C(C(=C(C(=C1OC(C1=C(C(=C(C=C1)F)F)NC1=C(C=C(C=C1)I)Cl)=O)F)F)F)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
To a solution of the product of Example 2, Step A, 2-(2-chloro-4-iodophenylamino)-3,4-difluorobenzoic acid (10.0 g, 24.4 mmol), and pyridine (2.16 mL, 26.8 mmol) in anhydrous dimethylformamide (49 mL) was added pentafluorophenyl trifluoroacetate (5.35 mL, 30.5 mmol). The resultant solution was stirred at ambient temper...
10.6084/m9.figshare.5104873.v1
null
Trifluoro group.Carboxylic acid.Ester
Ester
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1.c1ccccc1
HF
CN(C=O)C.C(C)(=O)OCC
null
null
O=C(O)c1ccc(F)c(F)c1Nc1ccc(I)cc1Cl.O=C(Oc1c(F)c(F)c(F)c(F)c1F)C(F)(F)F>CN(C=O)C.C(C)(=O)OCC>O=C(Oc1c(F)c(F)c(F)c(F)c1F)c1ccc(F)c(F)c1Nc1ccc(I)cc1Cl
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-67ba23b4a90d4811a82556d842bf0a11
NOCCO.O=C(Oc1c(F)c(F)c(F)c(F)c1F)c1ccc(F)c(F)c1Nc1ccc(I)cc1Cl>>O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(I)cc1Cl
C(C)(C)N(C(C)C)CC.FC1=C(C(=C(C(=C1OC(C1=C(C(=C(C=C1)F)F)NC1=C(C=C(C=C1)I)Cl)=O)F)F)F)F.FC1=C(C(=C(C(=C1OC(C1=C(C(=C(C=C1)F)F)NC1=C(C=C(C=C1)I)Cl)=O)F)F)F)F.NOCCO>>ClC1=C(C=CC(=C1)I)NC1=C(C(=O)NOCCO)C=CC(=C1F)F
[NH2:3][O:4][CH2:5][CH2:6][OH:7].Fc1c(F)c(F)c(O[C:2](=[O:1])[c:8]2[cH:9][cH:10][c:11]([F:12])[c:13]([F:14])[c:15]2[NH:16][c:17]2[cH:18][cH:19][c:20]([I:21])[cH:22][c:23]2[Cl:24])c(F)c1F>>[O:1]=[C:2]([NH:3][O:4][CH2:5][CH2:6][OH:7])[c:8]1[cH:9][cH:10][c:11]([F:12])[c:13]([F:14])[c:15]1[NH:16][c:17]1[cH:18][cH:19][c:20](...
NOCCO.O=C(Oc1c(F)c(F)c(F)c(F)c1F)c1ccc(F)c(F)c1Nc1ccc(I)cc1Cl
O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(I)cc1Cl
null
null
CN(C=O)C
Acylation
Aminolysis of esters
bee80c17ba750e5b878660daaf03b34b83cc65c10d42a24fde7726a66e741f89
f21fd5f8c88779686ca0dcd2a6ec464a4e9cd0b9a76d99bbd673ae535081dde3
c1ccc(Nc2ccccc2)cc1
F-c1:c(-F):c(-F):c(-O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]):c(-F):c:1-F.[C:6]-[#8:7]-[NH2;D1;+0:8]>>[C:6]-[#8:7]-[NH;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
90
[{"value": 90.0, "product": "ClC1=C(C=CC(=C1)I)NC1=C(C(=O)NOCCO)C=CC(=C1F)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
To a solution of the product of Example 2, Step B, 2-(2-chloro-4-iodo-phenylamino)-3,4-difluorobenzoic acid pentafluorophenyl ester (10.0 g, 17.4 mmol), in anhydrous dimethylformamide (36 mL) was added 2-(aminooxy)-ethanol [prepared by the literature procedure: Dhanak, D.; Reese, C. B., J. Chem. Soc., Perkin Trans. 198...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Aromatic halide.Aromatic halide.Aromatic halide.Ester.Primary amine
Secondary amide
c1ccccc1
null
c1ccccc1.c1ccccc1
HF
CN(C=O)C
null
null
NOCCO.O=C(Oc1c(F)c(F)c(F)c(F)c1F)c1ccc(F)c(F)c1Nc1ccc(I)cc1Cl>CN(C=O)C>O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(I)cc1Cl
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-73439d27f39b4390aed46e812a67376f
C=Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(Cl)c1>>CCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(Cl)c1
ClC1=C(C=CC(=C1)C=C)NC1=C(C(=O)NOCCO)C=CC(=C1F)F.ClC1=C(C=CC(=C1)C=C)NC1=C(C(=O)NOCCO)C=CC(=C1F)F>>ClC1=C(C=CC(=C1)CC)NC1=C(C(=O)NOCCO)C=CC(=C1F)F
[CH2:1]=[CH:2][c:3]1[cH:4][cH:5][c:6]([NH:7][c:8]2[c:9]([C:10](=[O:11])[NH:12][O:13][CH2:14][CH2:15][OH:16])[cH:17][cH:18][c:19]([F:20])[c:21]2[F:22])[c:23]([Cl:24])[cH:25]1>>[CH3:1][CH2:2][c:3]1[cH:4][cH:5][c:6]([NH:7][c:8]2[c:9]([C:10](=[O:11])[NH:12][O:13][CH2:14][CH2:15][OH:16])[cH:17][cH:18][c:19]([F:20])[c:21]2[F...
C=Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(Cl)c1
CCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(Cl)c1
null
[Pd]
O1CCCC1.CO
Reduction
Hydrogenation (double to single)
8276b4fb5ddc7d15dec6d92474e91e2dbb2fb8b81e5b5720762e5d89cb27aa69
1ccae9f2e86499601fc3421041ff4588c8e6fd53048e86c3b6ed12ae873609c0
c1ccc(Nc2ccccc2)cc1
[CH2;D1;+0:1]=[CH;D2;+0:2]-[c:3](:[c:4]):[c:5]>>[CH3;D1;+0:1]-[CH2;D2;+0:2]-[c:3](:[c:4]):[c:5]
null
[]
null
null
6
HOUR
A solution of the product of Example 2, Step D, 2-(2-chloro-4-vinyl-phenylamino)-3,4-difluoro-N-(2-hydroxy-ethoxy)-benzamide (0.291 g, 0.789 mmol) in tetrahydrofuran (16 mL) was hydrogenated over 10% palladium on carbon (0.08 g) at 6900 psig at room temperature for 17 hours. The catalyst was removed by filtration and t...
10.6084/m9.figshare.5104873.v1
null
Vinyl
null
null
null
c1ccccc1.c1ccccc1
null
[Pd].O1CCCC1.CO
null
6
C=Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(Cl)c1>[Pd].O1CCCC1.CO>CCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(Cl)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-652bcc1582d54f0ca58d7b36a9a67c78
Cc1ccc(N)c(F)c1.O=C(O)c1ccc(F)c(F)c1F>>Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
FC1=C(C(=O)O)C=CC(=C1F)F.FC1=C(N)C=CC(=C1)C.[Li+].C[Si](C)(C)[N-][Si](C)(C)C>>FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)C)F
[CH3:1][c:2]1[cH:3][cH:4][c:5]([NH2:6])[c:18]([F:19])[cH:20]1.F[c:7]1[c:8]([C:9](=[O:10])[OH:11])[cH:12][cH:13][c:14]([F:15])[c:16]1[F:17]>>[CH3:1][c:2]1[cH:3][cH:4][c:5]([NH:6][c:7]2[c:8]([C:9](=[O:10])[OH:11])[cH:12][cH:13][c:14]([F:15])[c:16]2[F:17])[c:18]([F:19])[cH:20]1
Cc1ccc(N)c(F)c1.O=C(O)c1ccc(F)c(F)c1F
Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
da9dae6a655c4bd18887b692f91621e77027436294d6e1fc7be7295afb364796
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(Nc2ccccc2)cc1
F-[c;H0;D3;+0:1](:[c:2](-[F;D1;H0:3]):[c:4]):[c:5](-[C:6](=[O;D1;H0:7])-[O;D1;H1:8]):[c:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[F;D1;H0:3]-[c:2](:[c:4]):[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[c:5](-[C:6](=[O;D1;H0:7])-[O;D1;H1:8]):[c:9]
null
[]
null
null
null
null
2,3,4-Trifluorobenzoic acid and 2-fluoro-4-methylaniline were reacted in the presence of LiHMDS solution in THF by the general procedure of Example 1, Step B. After workup, 3,4-difluoro-2-[2-fluoro-4-methylanilino]benzoic acid was isolated as a crude pale brown solid which was reacted directly with 2-(aminooxy)ethanol ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HF
C1CCOC1
null
null
Cc1ccc(N)c(F)c1.O=C(O)c1ccc(F)c(F)c1F>C1CCOC1>Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-2bae50fd47ff4a1cbb15b2e0c82c7bc1
C#Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1>>C=Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
C(#C)C1=CC(=C(C=C1)NC1=C(C(=O)O)C=CC(=C1F)F)F.N1=CC=CC2=CC=CC=C12>>FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)C=C)F
[CH:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([NH:7][c:8]2[c:9]([C:10](=[O:11])[OH:12])[cH:13][cH:14][c:15]([F:16])[c:17]2[F:18])[c:19]([F:20])[cH:21]1>>[CH2:1]=[CH:2][c:3]1[cH:4][cH:5][c:6]([NH:7][c:8]2[c:9]([C:10](=[O:11])[OH:12])[cH:13][cH:14][c:15]([F:16])[c:17]2[F:18])[c:19]([F:20])[cH:21]1
C#Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
C=Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
null
[Pd].CC(=O)[O-].CC(=O)[O-].[Pb+2]
C1CCOC1
Reduction
Hydrogenation (triple to double)
9fb9e3bcd1979ce1ec380a62b41fc2baa9493f4b62d173fd793175200be9b0be
d06db8777adee8a754da5dc5b637b0f3c536c729d38bcda44c5eb217b809e799
c1ccc(Nc2ccccc2)cc1
[CH;D1;+0:1]#[C;H0;D2;+0:2]-[c:3](:[c:4]):[c:5]>>[CH2;D1;+0:1]=[CH;D2;+0:2]-[c:3](:[c:4]):[c:5]
72
[{"value": 72.0, "product": "FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)C=C)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 71.5, "product": "FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)C=C)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
15
MINUTE
The product of Example 1, Step C, 2-[(4-ethynyl-2-fluorophenyl)amino]-3,4-difluorobenzoic acid (540 mg, 1.86 mmol) and quinoline (220 mg) were dissolved in THF (50 mL), then Lindlar catalyst (11 mg) added. This mixture was stirred under an atmosphere of hydrogen (60 psi) for 3 periods of 15 minutes and monitored carefu...
10.6084/m9.figshare.5104873.v1
null
Alkyne
Vinyl
null
null
c1ccccc1.c1ccccc1
null
[Pd].CC(=O)[O-].CC(=O)[O-].[Pb+2].C1CCOC1
null
0.25
C#Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1>[Pd].CC(=O)[O-].CC(=O)[O-].[Pb+2].C1CCOC1>C=Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-6cd6518d59e44a37a1277486b0c0d90a
C=Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO>>C=Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)C=C)F.C1=CN(C=N1)C(=O)N2C=CN=C2.NOCCO>>FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)C=C)F
O[C:10]([c:9]1[c:8]([NH:7][c:6]2[cH:5][cH:4][c:3]([CH:2]=[CH2:1])[cH:25][c:23]2[F:24])[c:21]([F:22])[c:19]([F:20])[cH:18][cH:17]1)=[O:11].[NH2:12][O:13][CH2:14][CH2:15][OH:16]>>[CH2:1]=[CH:2][c:3]1[cH:4][cH:5][c:6]([NH:7][c:8]2[c:9]([C:10](=[O:11])[NH:12][O:13][CH2:14][CH2:15][OH:16])[cH:17][cH:18][c:19]([F:20])[c:21]2...
C=Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO
C=Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
null
null
null
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
c1ccc(Nc2ccccc2)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C:6]-[#8:7]-[NH2;D1;+0:8]>>[C:6]-[#8:7]-[NH;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
78
[{"value": 78.0, "product": "FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)C=C)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was prepared from reaction of the product of Example 4, Step A, 3,4-difluoro-2-[(2-fluoro-4-vinylphenyl)amino]benzoic acid with CDI and 2-(aminooxy)ethanol by the general procedure of Example 1, Step E, then purified by flash column chromatography on silica gel (10% EtOAc/hexanes) to give 3,4-difluor...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccccc1.c1ccccc1
HO-
null
null
null
C=Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO>>C=Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-05e03083de6c4618867870fed822e0e5
COCCOC.O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(I)cc1F>>C=Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)I)F.C(OC)COC.O.C(=O)([O-])[O-].[K+].[K+].O.[B]>>C(=C)C1=CC(=C(C=C1)NC1=C(C(=O)NOCCO)C=CC(=C1F)F)F
COCCO[CH3:1].I[c:3]1[cH:4][cH:5][c:6]([NH:7][c:8]2[c:9]([C:10](=[O:11])[NH:12][O:13][CH2:14][CH2:15][OH:16])[cH:17][cH:18][c:19]([F:20])[c:21]2[F:22])[c:23]([F:24])[cH:25]1>>[CH2:1]=[CH:2][c:3]1[cH:4][cH:5][c:6]([NH:7][c:8]2[c:9]([C:10](=[O:11])[NH:12][O:13][CH2:14][CH2:15][OH:16])[cH:17][cH:18][c:19]([F:20])[c:21]2[F:...
COCCOC.O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(I)cc1F
C=Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
null
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1
[Cl-].[Na+].O
C-C Coupling
OtherReaction
63d3206d581071ef7b7bb23b8ca08334fbab0b6c6d066dc8a9ac56ee0ddb7824
23c65ae2aa282ff569a38af7d0cad288cbe289bcf57e497c7f4b894b7dbcb571
c1ccc(Nc2ccccc2)cc1
C-O-C-C-O-[CH3;D1;+0:1].I-[c;H0;D3;+0:2](:[c:3]:[c:4]):[c:5]:[c:6]>>[CH2;D1;+0:1]=[C:7]-[c;H0;D3;+0:2](:[c:3]:[c:4]):[c:5]:[c:6]
76
[{"value": 76.0, "product": "C(=C)C1=CC(=C(C=C1)NC1=C(C(=O)NOCCO)C=CC(=C1F)F)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
20
MINUTE
3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-benzamide (1.00 g, 2.21 mmol) was dissolved in dry dimethoxyethane (DME, 18 ml) under a nitrogen atmosphere, Pd(Ph3P)4 (0.13 g, 0.11 mmol) was added and the resulting yellow solution was stirred at ambient temperature for 20 min. K2CO3 (−325 mesh, 0.31 g...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Ether.Ether
Vinyl
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HI
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.[Cl-].[Na+].O
null
0.333333
COCCOC.O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(I)cc1F>C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.[Cl-].[Na+].O>C=Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-2dc6b170e3ac4f2cbf2e0c712791378e
C=C[CH2][Sn]([CH2]CCC)([CH2]CCC)[CH2]CCC.COC(=O)c1ccc(F)c(F)c1Nc1ccc(I)cc1F>>C=CCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
Cl.O1CCOCC1.C(C=C)[Sn](CCCC)(CCCC)CCCC.FC=1C(=C(C(=O)OC)C=CC1F)NC1=C(C=C(C=C1)I)F>>C(C=C)C1=CC(=C(NC2=C(C(=O)O)C=CC(=C2F)F)C=C1)F
CCC[CH2][Sn]([CH2]CCC)([CH2]CCC)[CH2:3][CH:2]=[CH2:1].C[O:13][C:11]([c:10]1[c:9]([NH:8][c:7]2[cH:6][cH:5][c:4](I)[cH:22][c:20]2[F:21])[c:18]([F:19])[c:16]([F:17])[cH:15][cH:14]1)=[O:12]>>[CH2:1]=[CH:2][CH2:3][c:4]1[cH:5][cH:6][c:7]([NH:8][c:9]2[c:10]([C:11](=[O:12])[OH:13])[cH:14][cH:15][c:16]([F:17])[c:18]2[F:19])[c:2...
C=C[CH2][Sn]([CH2]CCC)([CH2]CCC)[CH2]CCC.COC(=O)c1ccc(F)c(F)c1Nc1ccc(I)cc1F
C=CCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
null
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1
O.CCO.[OH-].[Na+]
C-C Coupling
OtherReaction
9844ab3c1e1bce74e59a0bb4609e30f2e92db385fb12d8c99463ca9efeaf158b
fe5f5a8472b016fdb14f74f8a0f437bcda3556c00d888a32c2afe280635279e6
c1ccc(Nc2ccccc2)cc1
C-C-C-[CH2]-[Sn](-[CH2;D2;+0:1]-[C:2]=[C;D1;H2:3])(-[CH2]-C-C-C)-[CH2]-C-C-C.C-[O;H0;D2;+0:4]-[C:5](=[O;D1;H0:6])-[c:7].I-[c;H0;D3;+0:8](:[c:9]:[c:10]):[c:11]:[c:12]>>[C;D1;H2:3]=[C:2]-[CH2;D2;+0:1]-[c;H0;D3;+0:8](:[c:9]:[c:10]):[c:11]:[c:12].[O;D1;H0:6]=[C:5](-[OH;D1;+0:4])-[c:7]
77.2
[{"value": 72.0, "product": "C(C=C)C1=CC(=C(NC2=C(C(=O)O)C=CC(=C2F)F)C=C1)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 77.2, "product": "C(C=C)C1=CC(=C(NC2=C(C(=O)O)C=CC(=C2F)F)C=C1)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
Methyl 3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzoate (1.00 g), 2.45 mmol) and (Ph3P)4Pd (568 mg, 0.49 mmol) were weighed into a dry flask which was fitted with a condensor and flushed with nitrogen. Dioxane (20 mL) and allyltributyltin (976 mg, 2.95 mmol) were added via syringe and the entire mixture heated at reflux...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Ester.Allyl.Tin
Carboxylic acid.Allyl
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HI.Sn
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.O.CCO.[OH-].[Na+]
null
8
C=C[CH2][Sn]([CH2]CCC)([CH2]CCC)[CH2]CCC.COC(=O)c1ccc(F)c(F)c1Nc1ccc(I)cc1F>C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.O.CCO.[OH-].[Na+]>C=CCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-bee613de47d04e23943809275f1c17bb
C=CCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO>>C=CCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
[Cl-].COC1=NC(=NC(=N1)OC)[N+]1(CCOCC1)C.NOCCO.C(C=C)C1=CC(=C(NC2=C(C(=O)O)C=CC(=C2F)F)C=C1)F.[Cl-].COC1=NC(=NC(=N1)OC)[N+]1(CCOCC1)C>>C(C=C)C1=CC(=C(NC2=C(C(=O)NOCCO)C=CC(=C2F)F)C=C1)F
O[C:11]([c:10]1[c:9]([NH:8][c:7]2[cH:6][cH:5][c:4]([CH2:3][CH:2]=[CH2:1])[cH:26][c:24]2[F:25])[c:22]([F:23])[c:20]([F:21])[cH:19][cH:18]1)=[O:12].[NH2:13][O:14][CH2:15][CH2:16][OH:17]>>[CH2:1]=[CH:2][CH2:3][c:4]1[cH:5][cH:6][c:7]([NH:8][c:9]2[c:10]([C:11](=[O:12])[NH:13][O:14][CH2:15][CH2:16][OH:17])[cH:18][cH:19][c:20...
C=CCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO
C=CCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
null
null
CO
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
c1ccc(Nc2ccccc2)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C:6]-[#8:7]-[NH2;D1;+0:8]>>[C:6]-[#8:7]-[NH;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
88
[{"value": 88.0, "product": "C(C=C)C1=CC(=C(NC2=C(C(=O)NOCCO)C=CC(=C2F)F)C=C1)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 87.9, "product": "C(C=C)C1=CC(=C(NC2=C(C(=O)NOCCO)C=CC(=C2F)F)C=C1)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
15
HOUR
2-(4-Allyl-2-fluoroanilino)-3,4-difluorobenzoic acid (700 mg, 2.28 mmol) was dissolved in MeOH (20 mL) to which was added 2-(aminooxy)ethanol (263 mg, 3.42 mmol), followed by 4-(4,6-dimethoxy-1,3,5-triazin-2-yl)-4-methymorpholinium chloride [DMT-MM, prepared according to the procedure of Kunishima et al [Tetrahedron, 5...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccccc1.c1ccccc1
HO-
CO
null
15
C=CCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO>CO>C=CCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-efdf57ef69424c9cb693f35b63f73eb8
C#Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO>>C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
[N-]1C=NC=C1.FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)C#C)F.NOCCO.C(=O)(N1C=NC=C1)N1C=NC=C1>>C(#C)C1=CC(=C(C=C1)NC1=C(C(=O)NOCCO)C=CC(=C1F)F)F
O[C:10]([c:9]1[c:8]([NH:7][c:6]2[cH:5][cH:4][c:3]([C:2]#[CH:1])[cH:25][c:23]2[F:24])[c:21]([F:22])[c:19]([F:20])[cH:18][cH:17]1)=[O:11].[NH2:12][O:13][CH2:14][CH2:15][OH:16]>>[CH:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([NH:7][c:8]2[c:9]([C:10](=[O:11])[NH:12][O:13][CH2:14][CH2:15][OH:16])[cH:17][cH:18][c:19]([F:20])[c:21]2[F:2...
C#Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO
C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
null
null
C1CCOC1
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
c1ccc(Nc2ccccc2)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C:6]-[#8:7]-[NH2;D1;+0:8]>>[C:6]-[#8:7]-[NH;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
55.2
[{"value": 55.0, "product": "C(#C)C1=CC(=C(C=C1)NC1=C(C(=O)NOCCO)C=CC(=C1F)F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 55.2, "product": "C(#C)C1=CC(=C(C=C1)NC1=C(C(=O)NOCCO)C=CC(=C1F)F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
10
MINUTE
The product of Example 1, Step C, 3,4-difluoro-2-[(4-ethynyl-2-fluorophenyl)amino]benzoic acid (349 mg, 1.20 mmol) was dissolved in dry THF (15 mL), to which was added carbonyldiimidazole (CDI) (389 mg, 2.40 mmol). Within 10 minutes, a bright yellow solution was obtained and conversion to the imidazolide was confirmed ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccccc1.c1ccccc1
HO-
C1CCOC1
null
0.166667
C#Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO>C1CCOC1>C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-940f3b3425414b03972be03656888992
C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1>>CCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
C(#C)C1=CC(=C(C=C1)NC1=C(C(=O)NOCCO)C=CC(=C1F)F)F>>C(C)C1=CC(=C(C=C1)NC1=C(C(=O)NOCCO)C=CC(=C1F)F)F
[CH:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([NH:7][c:8]2[c:9]([C:10](=[O:11])[NH:12][O:13][CH2:14][CH2:15][OH:16])[cH:17][cH:18][c:19]([F:20])[c:21]2[F:22])[c:23]([F:24])[cH:25]1>>[CH3:1][CH2:2][c:3]1[cH:4][cH:5][c:6]([NH:7][c:8]2[c:9]([C:10](=[O:11])[NH:12][O:13][CH2:14][CH2:15][OH:16])[cH:17][cH:18][c:19]([F:20])[c:21]2[F:22...
C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
CCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
null
[Pd]
CO.C1CCOC1
Reduction
OtherReaction
2bb8d5b532a2781e0a7c069a5cd3e8a7e8d44660c0ec1d9e17c04d8ba2cb383b
1990560e9c55934bde8ca0feaed9c61d80f37f94f0cf240a9929dc374d0a33aa
c1ccc(Nc2ccccc2)cc1
[CH;D1;+0:1]#[C;H0;D2;+0:2]-[c:3](:[c:4]):[c:5]>>[CH3;D1;+0:1]-[CH2;D2;+0:2]-[c:3](:[c:4]):[c:5]
null
[]
null
null
14.8
HOUR
A mixture of the product of Example 7A, 2-[(4-ethynyl-2-fluorophenyl)amino]-3,4-difluoro-N-(2-hydroxy-ethoxy)benzamide (11.0 g, 31.40 mmol), Pd—C (10%, 1.0 g) in THF (100 mL) and MeOH (100 mL) was subject to hydrogenation (25 psi) for 14.8 hrs (The reaction was followed by HPLC until all SM peak disappeared.). The mixt...
10.6084/m9.figshare.5104873.v1
null
Alkyne
null
null
null
c1ccccc1.c1ccccc1
null
[Pd].CO.C1CCOC1
null
14.8
C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1>[Pd].CO.C1CCOC1>CCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a1c05f4c5d514d3ca0e088de67bfd785
C#C[Si](C)(C)C.O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(I)cc1Cl>>C[Si](C)(C)C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(Cl)c1
ClC1=C(C=CC(=C1)I)NC1=C(C(=O)NOCCO)C=CC(=C1F)F.ClC1=C(C=CC(=C1)I)NC1=C(C(=O)NOCCO)C=CC(=C1F)F.C[Si](C)(C)C#C>>ClC1=C(C=CC(=C1)C#C[Si](C)(C)C)NC1=C(C(=O)NOCCO)C=CC(=C1F)F
[CH3:1][Si:2]([CH3:3])([CH3:4])[C:5]#[CH:6].I[c:7]1[cH:8][cH:9][c:10]([NH:11][c:12]2[c:13]([C:14](=[O:15])[NH:16][O:17][CH2:18][CH2:19][OH:20])[cH:21][cH:22][c:23]([F:24])[c:25]2[F:26])[c:27]([Cl:28])[cH:29]1>>[CH3:1][Si:2]([CH3:3])([CH3:4])[C:5]#[C:6][c:7]1[cH:8][cH:9][c:10]([NH:11][c:12]2[c:13]([C:14](=[O:15])[NH:16]...
C#C[Si](C)(C)C.O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(I)cc1Cl
C[Si](C)(C)C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(Cl)c1
null
Cl[Pd]([P](C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3)([P](C4=CC=CC=C4)(C5=CC=CC=C5)C6=CC=CC=C6)Cl
C(C)N(CC)CC
C-C Coupling
Sonogashira alkyne_aryl halide
15c08902746c61a960c314898ce6bb5fcc5e189f9e057388c59dba9ec9d0c81c
305eca0fd2975da49e7f69e4edfb9dc1cbce82513954bc5a73be3289e70e5f76
c1ccc(Nc2ccccc2)cc1
I-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[C;D1;H3:6]-[#14:7](-[C;D1;H3:8])(-[C;D1;H3:9])-[C:10]#[CH;D1;+0:11]>>[C;D1;H3:6]-[#14:7](-[C;D1;H3:8])(-[C;D1;H3:9])-[C:10]#[C;H0;D2;+0:11]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5]
76
[{"value": 76.0, "product": "ClC1=C(C=CC(=C1)C#C[Si](C)(C)C)NC1=C(C(=O)NOCCO)C=CC(=C1F)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
20
MINUTE
The product of Example 2, Step C, 2-(2-chloro-4-iodo-phenylamino)-3,4-difluoro-N-(2-hydroxy-ethoxy)-benzamide (3.25 g, 6.93 mmol) and (trimethylsilyl)acetylene (1.10 mL, 7.78 mmol) were combined in triethylamine (17 mL). Dichlorobis(triphenylphosphine)-palladium(II) (0.120 g, 0.017 mol) and cuprous iodide (0.033 g, 0.1...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Alkyne
Alkyne
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HI
Cl[Pd]([P](C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3)([P](C4=CC=CC=C4)(C5=CC=CC=C5)C6=CC=CC=C6)Cl.C(C)N(CC)CC
null
0.333333
C#C[Si](C)(C)C.O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(I)cc1Cl>Cl[Pd]([P](C1=CC=CC=C1)(C2=CC=CC=C2)C3=CC=CC=C3)([P](C4=CC=CC=C4)(C5=CC=CC=C5)C6=CC=CC=C6)Cl.C(C)N(CC)CC>C[Si](C)(C)C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(Cl)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-abf0c5ff35c141c0a0a8eb3ff909fa59
C[Si](C)(C)C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(Cl)c1>>C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(Cl)c1
ClC1=C(C=CC(=C1)C#C[Si](C)(C)C)NC1=C(C(=O)NOCCO)C=CC(=C1F)F.ClC1=C(C=CC(=C1)C#C[Si](C)(C)C)NC1=C(C(=O)NOCCO)C=CC(=C1F)F.C(C)(=O)O.[F-].[Cs+]>>ClC1=C(C=CC(=C1)C#C)NC1=C(C(=O)NOCCO)C=CC(=C1F)F
C[Si](C)(C)[C:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([NH:7][c:8]2[c:9]([C:10](=[O:11])[NH:12][O:13][CH2:14][CH2:15][OH:16])[cH:17][cH:18][c:19]([F:20])[c:21]2[F:22])[c:23]([Cl:24])[cH:25]1>>[CH:1]#[C:2][c:3]1[cH:4][cH:5][c:6]([NH:7][c:8]2[c:9]([C:10](=[O:11])[NH:12][O:13][CH2:14][CH2:15][OH:16])[cH:17][cH:18][c:19]([F:20])[c:...
C[Si](C)(C)C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(Cl)c1
C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(Cl)c1
null
null
CO
Deprotection
TMS deprotection from alkyne
e85676bb81da384790c9c858d44f182cdd01e3a79f77f7a239fe38487234cb96
56d526d7c9cb1bd7bee4940e216a9b1dd4597fd025a186b8d6e4675d8f4db26b
c1ccc(Nc2ccccc2)cc1
C-[Si](-C)(-C)-[C;H0;D2;+0:1]#[C:2]-[c:3]>>[CH;D1;+0:1]#[C:2]-[c:3]
null
[]
null
null
26
HOUR
To a solution of the product of Example 8, Step A, 2-(2-Chloro-4-trimethylsilanylethynyl-phenylamino)-3,4-difluoro-N-(2-hydroxy-ethoxy)-benzamide (0.704 g, 1.60 mmol) in methanol (21 mL) was added acetic acid (0.1 mL) and cesium fluoride (0.600 g, 3.95 mmol). The resultant solution was stirred at ambient temperature. A...
10.6084/m9.figshare.5104873.v1
null
Alkyne.Silyl protective group
Alkyne
null
null
c1ccccc1.c1ccccc1
Other
CO
null
26
C[Si](C)(C)C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(Cl)c1>CO>C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(Cl)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-1d409171efd4418290188d6fe86a4dd7
C#CCN.O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(I)cc1F>>NCC#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
C(C#C)N.FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)I)F>>NCC#CC1=CC(=C(NC2=C(C(=O)NOCCO)C=CC(=C2F)F)C=C1)F
[NH2:1][CH2:2][C:3]#[CH:4].I[c:5]1[cH:6][cH:7][c:8]([NH:9][c:10]2[c:11]([C:12](=[O:13])[NH:14][O:15][CH2:16][CH2:17][OH:18])[cH:19][cH:20][c:21]([F:22])[c:23]2[F:24])[c:25]([F:26])[cH:27]1>>[NH2:1][CH2:2][C:3]#[C:4][c:5]1[cH:6][cH:7][c:8]([NH:9][c:10]2[c:11]([C:12](=[O:13])[NH:14][O:15][CH2:16][CH2:17][OH:18])[cH:19][c...
C#CCN.O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(I)cc1F
NCC#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
null
null
null
C-C Coupling
Sonogashira alkyne_aryl halide
15c08902746c61a960c314898ce6bb5fcc5e189f9e057388c59dba9ec9d0c81c
305eca0fd2975da49e7f69e4edfb9dc1cbce82513954bc5a73be3289e70e5f76
c1ccc(Nc2ccccc2)cc1
I-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[C:6]-[C:7]#[CH;D1;+0:8]>>[C:6]-[C:7]#[C;H0;D2;+0:8]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5]
100
[{"value": 100.0, "product": "NCC#CC1=CC(=C(NC2=C(C(=O)NOCCO)C=CC(=C2F)F)C=C1)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was prepared by Sonogashira reaction of propargyl amine and 3,4-difluoro-2-(2-fluoro-4-iodo-phenylamino)-N-(2-hydroxy-ethoxy)-benzamide by the general procedure of Example 1, Step A. The orange oil resulting from workup was purified by chromatography on silica gel (10% MeOH/CH2Cl2 as eluant), to give...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Alkyne
Alkyne
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HI
null
null
null
C#CCN.O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(I)cc1F>>NCC#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-0ff016bab27144549569c92e42e28f21
Nc1ccc(C#CCOC2CCCCO2)cc1F.O=C(O)c1ccc(F)c(F)c1F>>O=C(O)c1ccc(F)c(F)c1Nc1ccc(C#CCOC2CCCCO2)cc1F
FC1=C(C(=O)O)C=CC(=C1F)F.FC1=C(N)C=CC(=C1)C#CCOC1OCCCC1.[Li+].C[Si](C)(C)[N-][Si](C)(C)C>>FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)C#CCOC1OCCCC1)F
[NH2:12][c:13]1[cH:14][cH:15][c:16]([C:17]#[C:18][CH2:19][O:20][CH:21]2[CH2:22][CH2:23][CH2:24][CH2:25][O:26]2)[cH:27][c:28]1[F:29].F[c:11]1[c:4]([C:2](=[O:1])[OH:3])[cH:5][cH:6][c:7]([F:8])[c:9]1[F:10]>>[O:1]=[C:2]([OH:3])[c:4]1[cH:5][cH:6][c:7]([F:8])[c:9]([F:10])[c:11]1[NH:12][c:13]1[cH:14][cH:15][c:16]([C:17]#[C:18...
Nc1ccc(C#CCOC2CCCCO2)cc1F.O=C(O)c1ccc(F)c(F)c1F
O=C(O)c1ccc(F)c(F)c1Nc1ccc(C#CCOC2CCCCO2)cc1F
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
da9dae6a655c4bd18887b692f91621e77027436294d6e1fc7be7295afb364796
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
C(#Cc1ccc(Nc2ccccc2)cc1)COC1CCCCO1
F-[c;H0;D3;+0:1](:[c:2](-[C:3](=[O;D1;H0:4])-[O;D1;H1:5]):[c:6]):[c:7](-[F;D1;H0:8]):[c:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[F;D1;H0:8]-[c:7](:[c:9]):[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[c:2](-[C:3](=[O;D1;H0:4])-[O;D1;H1:5]):[c:6]
68
[{"value": 68.0, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
2,3,4-Trifluorobenzoic acid and 2-fluoro-4-[3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl]aniline were reacted in the presence of LiHMDS solution in THF by the general procedure of Example 1, Step B. After workup, followed by purification by chromatography on silica gel (50% EtOAc/PE as eluant), 3,4-difluoro-2-{2-fluoro-4...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1.C1CCOCC1
HF
C1CCOC1
null
null
Nc1ccc(C#CCOC2CCCCO2)cc1F.O=C(O)c1ccc(F)c(F)c1F>C1CCOC1>O=C(O)c1ccc(F)c(F)c1Nc1ccc(C#CCOC2CCCCO2)cc1F
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-1e3f5e894c964094bd2b7980d8d4d6f3
NOCCO.O=C(O)c1ccc(F)c(F)c1Nc1ccc(C#CCOC2CCCCO2)cc1F>>O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(C#CCOC2CCCCO2)cc1F
FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)C#CCOC1OCCCC1)F.C1=CN(C=N1)C(=O)N2C=CN=C2.NOCCO>>FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)C#CCOC1OCCCC1)F
[NH2:3][O:4][CH2:5][CH2:6][OH:7].O[C:2](=[O:1])[c:8]1[cH:9][cH:10][c:11]([F:12])[c:13]([F:14])[c:15]1[NH:16][c:17]1[cH:18][cH:19][c:20]([C:21]#[C:22][CH2:23][O:24][CH:25]2[CH2:26][CH2:27][CH2:28][CH2:29][O:30]2)[cH:31][c:32]1[F:33]>>[O:1]=[C:2]([NH:3][O:4][CH2:5][CH2:6][OH:7])[c:8]1[cH:9][cH:10][c:11]([F:12])[c:13]([F:...
NOCCO.O=C(O)c1ccc(F)c(F)c1Nc1ccc(C#CCOC2CCCCO2)cc1F
O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(C#CCOC2CCCCO2)cc1F
null
null
null
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
C(#Cc1ccc(Nc2ccccc2)cc1)COC1CCCCO1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C:6]-[#8:7]-[NH2;D1;+0:8]>>[C:6]-[#8:7]-[NH;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
69
[{"value": 69.0, "product": "FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)C#CCOC1OCCCC1)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was prepared from reaction of 3,4-difluoro-2-{2-fluoro-4-[3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl]anilino}benzoic acid with CDI and 2-(aminooxy)ethanol by the general procedure of Example 1, Step E, then purified by column chromatography on silica gel (50% EtOAc/PE) as eluant), to give 3,4-difluor...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccccc1.c1ccccc1.C1CCOCC1
HO-
null
null
null
NOCCO.O=C(O)c1ccc(F)c(F)c1Nc1ccc(C#CCOC2CCCCO2)cc1F>>O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(C#CCOC2CCCCO2)cc1F
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-443998a5f675458886606cde78f87851
O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(C#CCOC2CCCCO2)cc1F>>O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(C#CCO)cc1F
FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)C#CCOC1OCCCC1)F>>FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)C#CCO)F
C1CCC([O:24][CH2:23][C:22]#[C:21][c:20]2[cH:19][cH:18][c:17]([NH:16][c:15]3[c:8]([C:2](=[O:1])[NH:3][O:4][CH2:5][CH2:6][OH:7])[cH:9][cH:10][c:11]([F:12])[c:13]3[F:14])[c:26]([F:27])[cH:25]2)OC1>>[O:1]=[C:2]([NH:3][O:4][CH2:5][CH2:6][OH:7])[c:8]1[cH:9][cH:10][c:11]([F:12])[c:13]([F:14])[c:15]1[NH:16][c:17]1[cH:18][cH:19...
O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(C#CCOC2CCCCO2)cc1F
O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(C#CCO)cc1F
null
Cl
O.CCO
Reduction
Ether cleavage to primary alcohol
69ac283008defddd09d640f7879e86f66dd29371b5c835a2facf24163ef14e9f
a4561cbdd42f56679299e19ea8b11070a39a15f6a95fb8a877e677f11b7ff57f
c1ccc(Nc2ccccc2)cc1
[c:1]-[C:2]#[C:3]-[C:4]-[O;H0;D2;+0:5]-C1-C-C-C-C-O-1>>[OH;D1;+0:5]-[C:4]-[C:3]#[C:2]-[c:1]
100
[{"value": 100.0, "product": "FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)C#CCO)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 98.9, "product": "FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)C#CCO)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
8
HOUR
3,4-Difluoro-2-{2-fluoro-4-[3-(tetrahydro-2H-pyran-2-yloxy)-1-propynyl]anilino}-N-(2-hydroxyethoxy)benzamide (115 mg, 0.25 mmol) was dissolved in EtOH (4 mL) to which was added 1 M HCl (5 drops). This reaction mixture was stirred overnight at RT, then the mixture was diluted with water (50 mL) and extracted with EtOAc ...
10.6084/m9.figshare.5104873.v1
null
Ether.Ether
Primary alcohol
C1CCOCC1
null
c1ccccc1.c1ccccc1
HO-
Cl.O.CCO
null
8
O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(C#CCOC2CCCCO2)cc1F>Cl.O.CCO>O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(C#CCO)cc1F
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-17aba261fdd1485b9bacfe6e52bb4f75
Nc1ccc(C#CCCOC2CCCCO2)cc1F.O=C(O)c1ccc(F)c(F)c1F>>O=C(O)c1ccc(F)c(F)c1Nc1ccc(C#CCCOC2CCCCO2)cc1F
FC1=C(C(=O)O)C=CC(=C1F)F.FC1=C(N)C=CC(=C1)C#CCCOC1OCCCC1.[Li+].C[Si](C)(C)[N-][Si](C)(C)C>>FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)C#CCCOC1OCCCC1)F
[NH2:12][c:13]1[cH:14][cH:15][c:16]([C:17]#[C:18][CH2:19][CH2:20][O:21][CH:22]2[CH2:23][CH2:24][CH2:25][CH2:26][O:27]2)[cH:28][c:29]1[F:30].F[c:11]1[c:4]([C:2](=[O:1])[OH:3])[cH:5][cH:6][c:7]([F:8])[c:9]1[F:10]>>[O:1]=[C:2]([OH:3])[c:4]1[cH:5][cH:6][c:7]([F:8])[c:9]([F:10])[c:11]1[NH:12][c:13]1[cH:14][cH:15][c:16]([C:1...
Nc1ccc(C#CCCOC2CCCCO2)cc1F.O=C(O)c1ccc(F)c(F)c1F
O=C(O)c1ccc(F)c(F)c1Nc1ccc(C#CCCOC2CCCCO2)cc1F
null
null
CCOCC.CCCCCC
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
da9dae6a655c4bd18887b692f91621e77027436294d6e1fc7be7295afb364796
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
C(#Cc1ccc(Nc2ccccc2)cc1)CCOC1CCCCO1
F-[c;H0;D3;+0:1](:[c:2](-[C:3](=[O;D1;H0:4])-[O;D1;H1:5]):[c:6]):[c:7](-[F;D1;H0:8]):[c:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[F;D1;H0:8]-[c:7](:[c:9]):[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[c:2](-[C:3](=[O;D1;H0:4])-[O;D1;H1:5]):[c:6]
null
[]
null
null
null
null
2,3,4-Trifluorobenzoic acid and 2-fluoro-4-[4-(tetrahydro-2H-pyran-2-yloxy)-1-butynyl]aniline were reacted in the presence of LiHMDS solution by the general procedure of Example 1, Step B. After workup, followed by purification by column chromatography on silica gel (50% EtOAc as eluant), unreacted aniline (26%), follo...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1.C1CCOCC1
HF
CCOCC.CCCCCC
null
null
Nc1ccc(C#CCCOC2CCCCO2)cc1F.O=C(O)c1ccc(F)c(F)c1F>CCOCC.CCCCCC>O=C(O)c1ccc(F)c(F)c1Nc1ccc(C#CCCOC2CCCCO2)cc1F
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-56cd40aec004470d9237abd900b00daa
NOCCO.O=C(O)c1ccc(F)c(F)c1Nc1ccc(C#CCCOC2CCCCO2)cc1F.O=C(n1ccnc1)n1ccnc1>>O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(C#CCCO)cc1F.O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(C#CCCOC2CCCCO2)cc1F
FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)C#CCCOC1OCCCC1)F.C1=CN(C=N1)C(=O)N2C=CN=C2.NOCCO>>FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)C#CCCO)F.FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)C#CCCOC1OCCCC1)F
[NH2:31][O:32][CH2:33][CH2:34][OH:35].[O:1]=[C:2]([OH:4])[c:8]1[cH:9][cH:10][c:11]([F:12])[c:13]([F:14])[c:15]1[NH:16][c:17]1[cH:18][cH:19][c:20]([C:21]#[C:22][CH2:23][CH2:24][O:25][CH:54]2[CH2:55][CH2:56][CH2:57][CH2:58][O:59]2)[cH:26][c:27]1[F:28].n1[cH:5][cH:43][n:44]([C:30]([n:3]2[cH:41]n[cH:48][cH:49]2)=[O:29])[cH...
NOCCO.O=C(O)c1ccc(F)c(F)c1Nc1ccc(C#CCCOC2CCCCO2)cc1F.O=C(n1ccnc1)n1ccnc1
O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(C#CCCO)cc1F.O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(C#CCCOC2CCCCO2)cc1F
null
null
null
Acylation
OtherReaction
5fb95cee82a26dfaba6e7018d41e90867d30bb3af34775da82469a1c8bbc056d
6d390f3343af917fc24ba1a240c9ee274754782a0537624e103b6f40d10d3dce
C(#Cc1ccc(Nc2ccccc2)cc1)CCOC1CCCCO1.c1ccc(Nc2ccccc2)cc1
[C:1]#[C:2]-[C:3]-[C:4]-[O;H0;D2;+0:5]-[CH;D3;+0:6](-[#8:7]-[C:8])-[C:9]-[C:10].[O;D1;H0:11]=[C;H0;D3;+0:12](-[OH;D1;+0:13])-[c:14](:[c:15]):[c:16].[C:17]-[#8:18]-[NH2;D1;+0:19].[O;D1;H0:20]=[C;H0;D3;+0:21](-[n;H0;D3;+0:22]1:[cH;D2;+0:23]:n:[cH;D2;+0:24]:[cH;D2;+0:25]:1)-[n;H0;D3;+0:26]1:[cH;D2;+0:27]:[cH;D2;+0:28]:n:[...
null
[]
null
null
null
null
The title compound was prepared by reaction of 3,4-difluoro-2-{2-fluoro-4-[4-(tetrahydro-2H-pyran-2-yloxy)-1-butynyl]anilino}benzoic acid with CDI and 2-(aminooxy)ethanol by the general procedure of Example 1, Step E, then purified by column chromatography on silica gel (50% EtOAc/PE as eluant) to give 3,4-difluoro-2-{...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Ether.Ether.Primary amine
Aromatic halide.Aromatic halide.Aromatic halide.Ether.Ether.Secondary amide.Secondary amide.Primary alcohol.Primary alcohol.Secondary amine.Alkyne
C1CCOCC1.c1c[nH]cn1.c1c[nH]cn1
c1ccccc1.c1ccccc1.C1CCOCC1
c1ccccc1.c1ccccc1.c1ccccc1.c1ccccc1.C1CCOCC1
null
null
null
null
NOCCO.O=C(O)c1ccc(F)c(F)c1Nc1ccc(C#CCCOC2CCCCO2)cc1F.O=C(n1ccnc1)n1ccnc1>>O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(C#CCCO)cc1F.O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(C#CCCOC2CCCCO2)cc1F
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-2309c2bbab4d4155a5295bdf10122a8d
C#CC(C)(C)O.O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(I)cc1F>>CC(C)(O)C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)I)F.CC(C)(C#C)O>>FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)C#CC(C)(C)O)F
[CH3:1][C:2]([CH3:3])([OH:4])[C:5]#[CH:6].I[c:7]1[cH:8][cH:9][c:10]([NH:11][c:12]2[c:13]([C:14](=[O:15])[NH:16][O:17][CH2:18][CH2:19][OH:20])[cH:21][cH:22][c:23]([F:24])[c:25]2[F:26])[c:27]([F:28])[cH:29]1>>[CH3:1][C:2]([CH3:3])([OH:4])[C:5]#[C:6][c:7]1[cH:8][cH:9][c:10]([NH:11][c:12]2[c:13]([C:14](=[O:15])[NH:16][O:17...
C#CC(C)(C)O.O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(I)cc1F
CC(C)(O)C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
null
[Cu]I
CCOCC.CO
C-C Coupling
Sonogashira alkyne_aryl halide
15c08902746c61a960c314898ce6bb5fcc5e189f9e057388c59dba9ec9d0c81c
305eca0fd2975da49e7f69e4edfb9dc1cbce82513954bc5a73be3289e70e5f76
c1ccc(Nc2ccccc2)cc1
I-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[C:6]-[C:7]#[CH;D1;+0:8]>>[C:6]-[C:7]#[C;H0;D2;+0:8]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5]
97
[{"value": 97.0, "product": "FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)C#CC(C)(C)O)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
4
HOUR
3,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)benzamide, which can be prepared according to the procedure in PCT Publication No. WO 00/41505, and 2-methyl-3-butyn-2-ol were reacted in the presence of CuI and (PhP3)2Cl2 by the general procedure of Example 1, Step A, and the mixture stirred at RT for 4 h. Th...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Alkyne
Alkyne
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HI
[Cu]I.CCOCC.CO
null
4
C#CC(C)(C)O.O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(I)cc1F>[Cu]I.CCOCC.CO>CC(C)(O)C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-93773aa78aea4709b88b8a4e3c2a60c6
C#CC(C)(O)CC.O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(I)cc1F>>CCC(C)(O)C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)I)F.CC(C#C)(CC)O>>FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)C#CC(CC)(C)O)F
[CH3:1][CH2:2][C:3]([CH3:4])([OH:5])[C:6]#[CH:7].I[c:8]1[cH:9][cH:10][c:11]([NH:12][c:13]2[c:14]([C:15](=[O:16])[NH:17][O:18][CH2:19][CH2:20][OH:21])[cH:22][cH:23][c:24]([F:25])[c:26]2[F:27])[c:28]([F:29])[cH:30]1>>[CH3:1][CH2:2][C:3]([CH3:4])([OH:5])[C:6]#[C:7][c:8]1[cH:9][cH:10][c:11]([NH:12][c:13]2[c:14]([C:15](=[O:...
C#CC(C)(O)CC.O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(I)cc1F
CCC(C)(O)C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
null
[Cu]I
CCOCC.CO
C-C Coupling
Sonogashira alkyne_aryl halide
15c08902746c61a960c314898ce6bb5fcc5e189f9e057388c59dba9ec9d0c81c
305eca0fd2975da49e7f69e4edfb9dc1cbce82513954bc5a73be3289e70e5f76
c1ccc(Nc2ccccc2)cc1
I-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[C:6]-[C:7]#[CH;D1;+0:8]>>[C:6]-[C:7]#[C;H0;D2;+0:8]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5]
77
[{"value": 77.0, "product": "FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)C#CC(CC)(C)O)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
4
HOUR
3,4-difluoro-2-(2-fluoro-4-iodoanilino)-N-(2-hydroxyethoxy)benzamide which can be prepared according to the procedure in PCT Publication No. WO 00/41505, and 3-methyl-1-pentyn-3-ol were reacted in the presence of CuI and (PhP3)2PdCl2 by the general procedure of Example 1, Step A, and the mixture stirred at RT for 4 h. ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Alkyne
Alkyne
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HI
[Cu]I.CCOCC.CO
null
4
C#CC(C)(O)CC.O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(I)cc1F>[Cu]I.CCOCC.CO>CCC(C)(O)C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-703e0c7bf0ba48d2916d2a4a288c816a
NCC#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1>>NCCCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
NCC#CC1=CC(=C(NC2=C(C(=O)NOCCO)C=CC(=C2F)F)C=C1)F>>NCCCC1=CC(=C(NC2=C(C(=O)NOCCO)C=CC(=C2F)F)C=C1)F
[NH2:1][CH2:2][C:3]#[C:4][c:5]1[cH:6][cH:7][c:8]([NH:9][c:10]2[c:11]([C:12](=[O:13])[NH:14][O:15][CH2:16][CH2:17][OH:18])[cH:19][cH:20][c:21]([F:22])[c:23]2[F:24])[c:25]([F:26])[cH:27]1>>[NH2:1][CH2:2][CH2:3][CH2:4][c:5]1[cH:6][cH:7][c:8]([NH:9][c:10]2[c:11]([C:12](=[O:13])[NH:14][O:15][CH2:16][CH2:17][OH:18])[cH:19][c...
NCC#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
NCCCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
null
null
[Pd].CCO
Reduction
OtherReaction
2bb8d5b532a2781e0a7c069a5cd3e8a7e8d44660c0ec1d9e17c04d8ba2cb383b
1990560e9c55934bde8ca0feaed9c61d80f37f94f0cf240a9929dc374d0a33aa
c1ccc(Nc2ccccc2)cc1
[N;D1;H2:1]-[C:2]-[C;H0;D2;+0:3]#[C;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]>>[N;D1;H2:1]-[C:2]-[CH2;D2;+0:3]-[CH2;D2;+0:4]-[c:5](:[c:6]):[c:7]
46
[{"value": 46.0, "product": "NCCCC1=CC(=C(NC2=C(C(=O)NOCCO)C=CC(=C2F)F)C=C1)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The product of Example 9, 2-[4-(3-amino-1-propynyl)-2-fluoroanilino]-3,4-difluoro-N-(2-hydroxyethoxy)benzamide was dissolved in absolute EtOH and hydrogenated in the presence of 5% Pd/C by the general procedure of Example 1, Step D. Purification of the resulting oil was carried out by column chromatography on silica ge...
10.6084/m9.figshare.5104873.v1
null
Alkyne
null
null
null
c1ccccc1.c1ccccc1
null
[Pd].CCO
null
null
NCC#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1>[Pd].CCO>NCCCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3d3cfd5131e3410bbcdb5fd0eff6d6d5
C#CCO.COC(=O)c1ccc(F)c(F)c1Nc1ccc(I)cc1F>>COC(=O)c1ccc(F)c(F)c1Nc1ccc(C#CCO)cc1F
C(C#C)O.FC=1C(=C(C(=O)OC)C=CC1F)NC1=C(C=C(C=C1)I)F>>FC=1C(=C(C(=O)OC)C=CC1F)NC1=C(C=C(C=C1)C#CCO)F
[CH:18]#[C:19][CH2:20][OH:21].I[c:17]1[cH:16][cH:15][c:14]([NH:13][c:12]2[c:5]([C:3]([O:2][CH3:1])=[O:4])[cH:6][cH:7][c:8]([F:9])[c:10]2[F:11])[c:23]([F:24])[cH:22]1>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([F:9])[c:10]([F:11])[c:12]1[NH:13][c:14]1[cH:15][cH:16][c:17]([C:18]#[C:19][CH2:20][OH:21])[cH:22][c:23]...
C#CCO.COC(=O)c1ccc(F)c(F)c1Nc1ccc(I)cc1F
COC(=O)c1ccc(F)c(F)c1Nc1ccc(C#CCO)cc1F
null
null
null
C-C Coupling
Sonogashira alkyne_aryl halide
15c08902746c61a960c314898ce6bb5fcc5e189f9e057388c59dba9ec9d0c81c
305eca0fd2975da49e7f69e4edfb9dc1cbce82513954bc5a73be3289e70e5f76
c1ccc(Nc2ccccc2)cc1
I-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[C:6]-[C:7]#[CH;D1;+0:8]>>[C:6]-[C:7]#[C;H0;D2;+0:8]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5]
94
[{"value": 94.0, "product": "FC=1C(=C(C(=O)OC)C=CC1F)NC1=C(C=C(C=C1)C#CCO)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was prepared by Sonogashira reaction of propargyl alcohol and methyl 3,4-difluoro-2-(2-fluoro-4-iodoanilino)benzoate by the general procedure of Example 1, Step A. The oil resulting from workup was purified by chromatography on silica gel (20% EtOAc/PE as eluant), to give methyl 3,4-difluoro-2-[2-flu...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Alkyne
Alkyne
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HI
null
null
null
C#CCO.COC(=O)c1ccc(F)c(F)c1Nc1ccc(I)cc1F>>COC(=O)c1ccc(F)c(F)c1Nc1ccc(C#CCO)cc1F
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-c2fd9b05bc69478ca881d4e35f1b42be
COC(=O)c1ccc(F)c(F)c1Nc1ccc(C#CCO)cc1F>>COC(=O)c1ccc(F)c(F)c1Nc1ccc(CCCO)cc1F
FC=1C(=C(C(=O)OC)C=CC1F)NC1=C(C=C(C=C1)C#CCO)F>>FC=1C(=C(C(=O)OC)C=CC1F)NC1=C(C=C(C=C1)CCCO)F
[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([F:9])[c:10]([F:11])[c:12]1[NH:13][c:14]1[cH:15][cH:16][c:17]([C:18]#[C:19][CH2:20][OH:21])[cH:22][c:23]1[F:24]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([F:9])[c:10]([F:11])[c:12]1[NH:13][c:14]1[cH:15][cH:16][c:17]([CH2:18][CH2:19][CH2:20][OH:21])[cH:22][c:23]1[...
COC(=O)c1ccc(F)c(F)c1Nc1ccc(C#CCO)cc1F
COC(=O)c1ccc(F)c(F)c1Nc1ccc(CCCO)cc1F
null
null
[Pd].CCO
Reduction
OtherReaction
2bb8d5b532a2781e0a7c069a5cd3e8a7e8d44660c0ec1d9e17c04d8ba2cb383b
1990560e9c55934bde8ca0feaed9c61d80f37f94f0cf240a9929dc374d0a33aa
c1ccc(Nc2ccccc2)cc1
[O;D1;H1:1]-[C:2]-[C;H0;D2;+0:3]#[C;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]>>[O;D1;H1:1]-[C:2]-[CH2;D2;+0:3]-[CH2;D2;+0:4]-[c:5](:[c:6]):[c:7]
93
[{"value": 93.0, "product": "FC=1C(=C(C(=O)OC)C=CC1F)NC1=C(C=C(C=C1)CCCO)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Methyl 3,4-difluoro-2-[2-fluoro-4-(3-hydroxy-1-propynyl)anilino]benzoate was dissolved in absolute EtOH and hydrogenated in the presence of 5% Pd/C by the general procedure of Example 1, Step D. Purification of the resulting oil was carried out by column chromatography on silica gel (20% EtOAc/PE as eluant) to give met...
10.6084/m9.figshare.5104873.v1
null
Alkyne
null
null
null
c1ccccc1.c1ccccc1
null
[Pd].CCO
null
null
COC(=O)c1ccc(F)c(F)c1Nc1ccc(C#CCO)cc1F>[Pd].CCO>COC(=O)c1ccc(F)c(F)c1Nc1ccc(CCCO)cc1F
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b48c2cfe1c3e42d2a0c217f5c156ec51
C=COCCON.O=C(O)c1ccc(F)c(F)c1Nc1ccc(CCCO)cc1F>>C=COCCONC(=O)c1ccc(F)c(F)c1Nc1ccc(CCCO)cc1F
FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)CCCO)F.NOCCOC=C.C[N+]1(CCOCC1)C2=NC(=NC(=N2)OC)OC.[Cl-]>>FC=1C(=C(C(=O)NOCCOC=C)C=CC1F)NC1=C(C=C(C=C1)CCCO)F
[CH2:1]=[CH:2][O:3][CH2:4][CH2:5][O:6][NH2:7].O[C:8](=[O:9])[c:10]1[cH:11][cH:12][c:13]([F:14])[c:15]([F:16])[c:17]1[NH:18][c:19]1[cH:20][cH:21][c:22]([CH2:23][CH2:24][CH2:25][OH:26])[cH:27][c:28]1[F:29]>>[CH2:1]=[CH:2][O:3][CH2:4][CH2:5][O:6][NH:7][C:8](=[O:9])[c:10]1[cH:11][cH:12][c:13]([F:14])[c:15]([F:16])[c:17]1[N...
C=COCCON.O=C(O)c1ccc(F)c(F)c1Nc1ccc(CCCO)cc1F
C=COCCONC(=O)c1ccc(F)c(F)c1Nc1ccc(CCCO)cc1F
null
null
null
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
c1ccc(Nc2ccccc2)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C:6]-[#8:7]-[NH2;D1;+0:8]>>[C:6]-[#8:7]-[NH;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
46
[{"value": 46.0, "product": "FC=1C(=C(C(=O)NOCCOC=C)C=CC1F)NC1=C(C=C(C=C1)CCCO)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was prepared from reaction of 3,4-difluoro-2-[2-fluoro-4-(3-hydroxypropyl)anilino]benzoic acid with 1-[2-(aminooxy)ethoxy]ethylene and DMT-MM by the general procedure of Example 6, Step B, then purified by column chromatography on silica gel (20% EtOAc/PE as eluant) to give 3,4-difluoro-2-[2-fluoro-4...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccccc1.c1ccccc1
HO-
null
null
null
C=COCCON.O=C(O)c1ccc(F)c(F)c1Nc1ccc(CCCO)cc1F>>C=COCCONC(=O)c1ccc(F)c(F)c1Nc1ccc(CCCO)cc1F
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a17282e9a7c047d2bd19b7693a12a426
C=COCCONC(=O)c1ccc(F)c(F)c1Nc1ccc(CCCI)cc1F.CNC>>CN(C)CCCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
C(=O)([O-])[O-].[K+].[K+].CNC.Cl.[Na+].[Cl-].FC=1C(=C(C(=O)NOCCOC=C)C=CC1F)NC1=C(C=C(C=C1)CCCI)F>>CN(CCCC1=CC(=C(NC2=C(C(=O)NOCCO)C=CC(=C2F)F)C=C1)F)C
C=C[O:20][CH2:19][CH2:18][O:17][NH:16][C:14]([c:13]1[c:12]([NH:11][c:10]2[cH:9][cH:8][c:7]([CH2:6][CH2:5][CH2:4]I)[cH:29][c:27]2[F:28])[c:25]([F:26])[c:23]([F:24])[cH:22][cH:21]1)=[O:15].[CH3:1][NH:2][CH3:3]>>[CH3:1][N:2]([CH3:3])[CH2:4][CH2:5][CH2:6][c:7]1[cH:8][cH:9][c:10]([NH:11][c:12]2[c:13]([C:14](=[O:15])[NH:16][...
C=COCCONC(=O)c1ccc(F)c(F)c1Nc1ccc(CCCI)cc1F.CNC
CN(C)CCCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
null
null
O.CC(=O)N(C)C.CCO
Heteroatom Alkylation and Arylation
OtherReaction
ec14f640305641a4a365da0f794c766899026d32803845716c9aad4957b3e910
7b457ef06260012b6a578b0b100111ddb70017121857acb4be1c04046ed64590
c1ccc(Nc2ccccc2)cc1
C=C-[O;H0;D2;+0:1]-[C:2]-[C:3].I-[CH2;D2;+0:4]-[C:5]-[C:6].[C;D1;H3:7]-[NH;D2;+0:8]-[C;D1;H3:9]>>[C:6]-[C:5]-[CH2;D2;+0:4]-[N;H0;D3;+0:8](-[C;D1;H3:7])-[C;D1;H3:9].[C:3]-[C:2]-[OH;D1;+0:1]
36
[{"value": 36.0, "product": "CN(CCCC1=CC(=C(NC2=C(C(=O)NOCCO)C=CC(=C2F)F)C=C1)F)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
15
HOUR
3,4-Difluoro-2-[2-fluoro-4-(3-iodopropyl)anilino]-N-[2-(vinyloxy)ethoxy]benzamide (200 mg, 0.39 mmol) was dissolved in DMA (10 mL), to which was added dimethylamine (0.15 mL of a 40% solution in water). This mixture was stirred at RT for 15 hours, then the DMA removed under reduced pressure, affording a yellow oil. Thi...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ether.Secondary amine.Vinyl
Primary alcohol.Tertiary amine
null
null
c1ccccc1.c1ccccc1
HI
O.CC(=O)N(C)C.CCO
null
15
C=COCCONC(=O)c1ccc(F)c(F)c1Nc1ccc(CCCI)cc1F.CNC>O.CC(=O)N(C)C.CCO>CN(C)CCCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-25003a94f8114147ba64c74b46faf942
C=COCCONC(=O)c1ccc(F)c(F)c1Nc1ccc(CCCI)cc1F.CN>>CNCCCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
FC=1C(=C(C(=O)NOCCOC=C)C=CC1F)NC1=C(C=C(C=C1)CCCI)F.CN>>FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)CCCNC)F
C=C[O:19][CH2:18][CH2:17][O:16][NH:15][C:13]([c:12]1[c:11]([NH:10][c:9]2[cH:8][cH:7][c:6]([CH2:5][CH2:4][CH2:3]I)[cH:28][c:26]2[F:27])[c:24]([F:25])[c:22]([F:23])[cH:21][cH:20]1)=[O:14].[CH3:1][NH2:2]>>[CH3:1][NH:2][CH2:3][CH2:4][CH2:5][c:6]1[cH:7][cH:8][c:9]([NH:10][c:11]2[c:12]([C:13](=[O:14])[NH:15][O:16][CH2:17][CH...
C=COCCONC(=O)c1ccc(F)c(F)c1Nc1ccc(CCCI)cc1F.CN
CNCCCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
null
null
null
Heteroatom Alkylation and Arylation
OtherReaction
e35ad961f1e6d9861787b321abc3cacad15211219fc7a442b2c63e9cc68174b1
e6f261fd8878f8a8d14bee33bef7e6af925a72342ff9d3817ff3eacc59eda654
c1ccc(Nc2ccccc2)cc1
C=C-[O;H0;D2;+0:1]-[C:2]-[C:3].I-[CH2;D2;+0:4]-[C:5]-[C:6].[C;D1;H3:7]-[NH2;D1;+0:8]>>[C:6]-[C:5]-[CH2;D2;+0:4]-[NH;D2;+0:8]-[C;D1;H3:7].[C:3]-[C:2]-[OH;D1;+0:1]
32
[{"value": 32.0, "product": "FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)CCCNC)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The product of Example 15, Step E, 3,4-Difluoro-2-[2-fluoro-4-(3-iodopropyl)anilino]-N-[2-(vinyloxy)ethoxy]benzamide was reacted with methylamine and then deprotected according to the general procedure of Example 15, Step F, to afford 3,4-difluoro-2-{2-fluoro-4-[3-(methylamino)propyl] anilino}-N-(2-hydroxyethoxy)benzam...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ether.Primary amine.Vinyl
Primary alcohol.Secondary amine
null
null
c1ccccc1.c1ccccc1
HI
null
null
null
C=COCCONC(=O)c1ccc(F)c(F)c1Nc1ccc(CCCI)cc1F.CN>>CNCCCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-85064afb2c2d4ee08e4b9df3eb3468d1
COC(=O)c1ccc(N)cc1.O=C(O)c1ccc(F)c(F)c1F>>COC(=O)c1ccc(Nc2c(C(=O)O)ccc(F)c2F)cc1
FC1=C(C(=O)O)C=CC(=C1F)F.NC1=CC=C(C(=O)OC)C=C1.[Li+].C[Si](C)(C)[N-][Si](C)(C)C>>FC=1C(=C(C(=O)O)C=CC1F)NC1=CC=C(C=C1)C(=O)OC
[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([NH2:9])[cH:21][cH:22]1.F[c:10]1[c:11]([C:12](=[O:13])[OH:14])[cH:15][cH:16][c:17]([F:18])[c:19]1[F:20]>>[CH3:1][O:2][C:3](=[O:4])[c:5]1[cH:6][cH:7][c:8]([NH:9][c:10]2[c:11]([C:12](=[O:13])[OH:14])[cH:15][cH:16][c:17]([F:18])[c:19]2[F:20])[cH:21][cH:22]1
COC(=O)c1ccc(N)cc1.O=C(O)c1ccc(F)c(F)c1F
COC(=O)c1ccc(Nc2c(C(=O)O)ccc(F)c2F)cc1
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
da9dae6a655c4bd18887b692f91621e77027436294d6e1fc7be7295afb364796
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(Nc2ccccc2)cc1
F-[c;H0;D3;+0:1](:[c:2](-[C:3](=[O;D1;H0:4])-[O;D1;H1:5]):[c:6]):[c:7](-[F;D1;H0:8]):[c:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[F;D1;H0:8]-[c:7](:[c:9]):[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[c:2](-[C:3](=[O;D1;H0:4])-[O;D1;H1:5]):[c:6]
null
[]
null
null
null
null
2,3,4-Trifluorobenzoic acid and methyl 4-aminobenzoate were reacted in the presence of LiHMDS solution in THF by the general procedure of Example 1, Step B, to afford after workup, crude 3,4-difluoro-2-[[4-(methoxycarbonyl)-phenyl]amino]benzoic acid as a cream solid. This material was then coupled directly with 2-(amin...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HF
C1CCOC1
null
null
COC(=O)c1ccc(N)cc1.O=C(O)c1ccc(F)c(F)c1F>C1CCOC1>COC(=O)c1ccc(Nc2c(C(=O)O)ccc(F)c2F)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-8d18dcc7634a42be912c43fc3087cdf0
COC(=O)c1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)cc1>>O=C(O)c1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)cc1
Cl.FC1=C(C(=CC=C1F)C(=O)NOCCO)NC1=CC=C(C(=O)OC)C=C1.[OH-].[Na+]>>FC1=C(C(=CC=C1F)C(=O)NOCCO)NC1=CC=C(C(=O)O)C=C1
C[O:3][C:2](=[O:1])[c:4]1[cH:5][cH:6][c:7]([NH:8][c:9]2[c:10]([C:11](=[O:12])[NH:13][O:14][CH2:15][CH2:16][OH:17])[cH:18][cH:19][c:20]([F:21])[c:22]2[F:23])[cH:24][cH:25]1>>[O:1]=[C:2]([OH:3])[c:4]1[cH:5][cH:6][c:7]([NH:8][c:9]2[c:10]([C:11](=[O:12])[NH:13][O:14][CH2:15][CH2:16][OH:17])[cH:18][cH:19][c:20]([F:21])[c:22...
COC(=O)c1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)cc1
O=C(O)c1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)cc1
null
null
C(C)O
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(Nc2ccccc2)cc1
C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]>>[O;D1;H0:3]=[C:2](-[OH;D1;+0:1])-[c:4]
57
[{"value": 57.0, "product": "FC1=C(C(=CC=C1F)C(=O)NOCCO)NC1=CC=C(C(=O)O)C=C1", "details": "PERCENTYIELD", "is_desired": false}, {"value": 56.8, "product": "FC1=C(C(=CC=C1F)C(=O)NOCCO)NC1=CC=C(C(=O)O)C=C1", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
15
HOUR
The product of Example 17, Step A, methyl 4-[[2,3-difluoro-6-[[(2-hydroxyethoxy)amino]carbonyl]phenyl]amino]benzoate (306 mg, 0.84 mmol) was dissolved in ethanol (40 mL), to which was added 1 M NaOH solution (40 mL). This mixture was stirred at room temperature for 15 hours, then poured into 1 M HCl solution (100 mL). ...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.c1ccccc1
Other
C(C)O
null
15
COC(=O)c1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)cc1>C(C)O>O=C(O)c1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-84f9ed7f26984a379b554b4c90bb3f70
O=C(Oc1c(F)c(F)c(F)c(F)c1F)c1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)cc1>>O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(CO)cc1
Cl.FC1=C(C(=CC=C1F)C(=O)NOCCO)NC1=CC=C(C(=O)OC2=C(C(=C(C(=C2F)F)F)F)F)C=C1.[BH4-].[Na+]>>FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=CC=C(C=C1)CO
Fc1c(F)c(F)c(O[C:21]([c:20]2[cH:19][cH:18][c:17]([NH:16][c:15]3[c:8]([C:2](=[O:1])[NH:3][O:4][CH2:5][CH2:6][OH:7])[cH:9][cH:10][c:11]([F:12])[c:13]3[F:14])[cH:24][cH:23]2)=[O:22])c(F)c1F>>[O:1]=[C:2]([NH:3][O:4][CH2:5][CH2:6][OH:7])[c:8]1[cH:9][cH:10][c:11]([F:12])[c:13]([F:14])[c:15]1[NH:16][c:17]1[cH:18][cH:19][c:20]...
O=C(Oc1c(F)c(F)c(F)c(F)c1F)c1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)cc1
O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(CO)cc1
null
null
O.C1CCOC1
Reduction
Reduction of ester to primary alcohol
b575eec76a4c9ad8acb617ea1e7a79320fb3fbdc661ff7c5ebff9aea18f305c7
b3072e135d22925398f326e6f6481a4c91699920b3f0efb5c65dcb31aeadb549
c1ccc(Nc2ccccc2)cc1
F-c1:c(-F):c(-F):c(-O-[C;H0;D3;+0:1](=[O;H0;D1;+0:2])-[c:3](:[c:4]):[c:5]):c(-F):c:1-F>>[OH;D1;+0:2]-[CH2;D2;+0:1]-[c:3](:[c:4]):[c:5]
37
[{"value": 37.0, "product": "FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=CC=C(C=C1)CO", "details": "PERCENTYIELD", "is_desired": false}, {"value": 36.7, "product": "FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=CC=C(C=C1)CO", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
The product of Example 17, Step C, 2,3,4,5,6-pentafluorophenyl 4-[[2,3-difluoro-6-[[(2-hydroxyethoxy)amino]carbonyl]phenyl]amino]benzoate (150 mg, 0.29 mmol) was dissolved in THF (2 mL), then added dropwise to a solution of NaBH4 (110 mg, 2.90 mmol) in water (2 mL). This mixture was stirred at room temperature for 2 ho...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Aromatic halide.Aromatic halide.Aromatic halide.Ester
Primary alcohol
c1ccccc1
null
c1ccccc1.c1ccccc1
Other
O.C1CCOC1
null
2
O=C(Oc1c(F)c(F)c(F)c(F)c1F)c1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)cc1>O.C1CCOC1>O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(CO)cc1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a93240bc8b454d4bb2f7365f9cfe6b9f
COC(=O)c1ccc(F)c(F)c1Nc1ccc(CCO)cc1F>>O=C(O)c1ccc(F)c(F)c1Nc1ccc(CCO)cc1F
FC=1C(=C(C(=O)OC)C=CC1F)NC1=C(C=C(C=C1)CCO)F>>FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)CCO)F
C[O:3][C:2](=[O:1])[c:4]1[cH:5][cH:6][c:7]([F:8])[c:9]([F:10])[c:11]1[NH:12][c:13]1[cH:14][cH:15][c:16]([CH2:17][CH2:18][OH:19])[cH:20][c:21]1[F:22]>>[O:1]=[C:2]([OH:3])[c:4]1[cH:5][cH:6][c:7]([F:8])[c:9]([F:10])[c:11]1[NH:12][c:13]1[cH:14][cH:15][c:16]([CH2:17][CH2:18][OH:19])[cH:20][c:21]1[F:22]
COC(=O)c1ccc(F)c(F)c1Nc1ccc(CCO)cc1F
O=C(O)c1ccc(F)c(F)c1Nc1ccc(CCO)cc1F
null
null
CCO
Deprotection
Ester saponification (methyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccc(Nc2ccccc2)cc1
C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4]>>[O;D1;H0:3]=[C:2](-[OH;D1;+0:1])-[c:4]
93
[{"value": 93.0, "product": "FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)CCO)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Methyl 3,4-difluoro-2-[2-fluoro-4-(2-hydroxyethyl)anilino]benzoate was deprotected using EtOH/1 M NaOH as above to afford 3,4-difluoro-2-[2-fluoro-4-(2-hydroxyethyl)anilino]benzoic acid as a crystalline cream solid (93%); m.p. (EtOAc/hexane) 196–200° C. 1H NMR [400 MHz, (CD3)2SO] δ 13.67 (v br s, 1 H), 9.28 (br s, 1 H)...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccccc1.c1ccccc1
Other
CCO
null
null
COC(=O)c1ccc(F)c(F)c1Nc1ccc(CCO)cc1F>CCO>O=C(O)c1ccc(F)c(F)c1Nc1ccc(CCO)cc1F
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-f15fc43c037f4f37b8ec705d194eed15
NOCCO.O=C(O)c1ccc(F)c(F)c1Nc1ccc(CCO)cc1F>>O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(CCO)cc1F
FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)CCO)F.NOCCO.C[N+]1(CCOCC1)C2=NC(=NC(=N2)OC)OC.[Cl-]>>FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)CCO)F
[NH2:3][O:4][CH2:5][CH2:6][OH:7].O[C:2](=[O:1])[c:8]1[cH:9][cH:10][c:11]([F:12])[c:13]([F:14])[c:15]1[NH:16][c:17]1[cH:18][cH:19][c:20]([CH2:21][CH2:22][OH:23])[cH:24][c:25]1[F:26]>>[O:1]=[C:2]([NH:3][O:4][CH2:5][CH2:6][OH:7])[c:8]1[cH:9][cH:10][c:11]([F:12])[c:13]([F:14])[c:15]1[NH:16][c:17]1[cH:18][cH:19][c:20]([CH2:...
NOCCO.O=C(O)c1ccc(F)c(F)c1Nc1ccc(CCO)cc1F
O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(CCO)cc1F
null
null
CO
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
c1ccc(Nc2ccccc2)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C:6]-[#8:7]-[NH2;D1;+0:8]>>[C:6]-[#8:7]-[NH;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
57
[{"value": 57.0, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
3,4-Difluoro-2-[2-fluoro-4-(2-hydroxyethyl)anilino]benzoic acid was dissolved in MeOH and prepared from reaction with 2(aminooxy)ethanol and DMT-MM by the general procedure of Example 6, Step B, affording a crude yellow oil after workup which was purified by filtration through a plug of silica gel (100% EtOAc as eluant...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccccc1.c1ccccc1
HO-
CO
null
null
NOCCO.O=C(O)c1ccc(F)c(F)c1Nc1ccc(CCO)cc1F>CO>O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(CCO)cc1F
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-ac5dfe3769464fd4a6214661ea172ebc
O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(C#CCO)cc1F>>O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(CCCO)cc1F
FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)C#CCO)F>>FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)CCCO)F
[O:1]=[C:2]([NH:3][O:4][CH2:5][CH2:6][OH:7])[c:8]1[cH:9][cH:10][c:11]([F:12])[c:13]([F:14])[c:15]1[NH:16][c:17]1[cH:18][cH:19][c:20]([C:21]#[C:22][CH2:23][OH:24])[cH:25][c:26]1[F:27]>>[O:1]=[C:2]([NH:3][O:4][CH2:5][CH2:6][OH:7])[c:8]1[cH:9][cH:10][c:11]([F:12])[c:13]([F:14])[c:15]1[NH:16][c:17]1[cH:18][cH:19][c:20]([CH...
O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(C#CCO)cc1F
O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(CCCO)cc1F
null
[Pd]
CCO
Reduction
OtherReaction
2bb8d5b532a2781e0a7c069a5cd3e8a7e8d44660c0ec1d9e17c04d8ba2cb383b
1990560e9c55934bde8ca0feaed9c61d80f37f94f0cf240a9929dc374d0a33aa
c1ccc(Nc2ccccc2)cc1
[O;D1;H1:1]-[C:2]-[C;H0;D2;+0:3]#[C;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]>>[O;D1;H1:1]-[C:2]-[CH2;D2;+0:3]-[CH2;D2;+0:4]-[c:5](:[c:6]):[c:7]
73
[{"value": 73.0, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The product of Example 10, Step D, 3,4-Difluoro-2-[2-fluoro-4-(3-hydroxy-1-propynyl)anilino]-N-(2-hydroxyethoxy)-benzamide was hydrogenated in absolute EtOH in the presence of 5% Pd/C by the procedure of Example 1, Step D. An off-white solid was isolated which was purified by filtration through a plug of silica gel (Et...
10.6084/m9.figshare.5104873.v1
null
Alkyne
null
null
null
c1ccccc1.c1ccccc1
null
[Pd].CCO
null
null
O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(C#CCO)cc1F>[Pd].CCO>O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(CCCO)cc1F
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a3eb01a097864b2887c7d147dccbe10d
O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(C#CCCO)cc1F>>O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(CCCCO)cc1F
FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)C#CCCO)F>>FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)CCCCO)F
[O:1]=[C:2]([NH:3][O:4][CH2:5][CH2:6][OH:7])[c:8]1[cH:9][cH:10][c:11]([F:12])[c:13]([F:14])[c:15]1[NH:16][c:17]1[cH:18][cH:19][c:20]([C:21]#[C:22][CH2:23][CH2:24][OH:25])[cH:26][c:27]1[F:28]>>[O:1]=[C:2]([NH:3][O:4][CH2:5][CH2:6][OH:7])[c:8]1[cH:9][cH:10][c:11]([F:12])[c:13]([F:14])[c:15]1[NH:16][c:17]1[cH:18][cH:19][c...
O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(C#CCCO)cc1F
O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(CCCCO)cc1F
null
[Pd]
CCO
Reduction
OtherReaction
2bb8d5b532a2781e0a7c069a5cd3e8a7e8d44660c0ec1d9e17c04d8ba2cb383b
1990560e9c55934bde8ca0feaed9c61d80f37f94f0cf240a9929dc374d0a33aa
c1ccc(Nc2ccccc2)cc1
[C:1]-[C:2]-[C;H0;D2;+0:3]#[C;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]>>[C:1]-[C:2]-[CH2;D2;+0:3]-[CH2;D2;+0:4]-[c:5](:[c:6]):[c:7]
46
[{"value": 46.0, "product": "FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)CCCCO)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The product of Example 11, 3,4-Difluoro-2-[2-fluoro-4-(4-hydroxy-1-butynyl)anilino]-N-(2-hydroxyethoxy)-benzamide was hydrogenated in absolute EtOH in the presence of 5% Pd/C by the procedure of Example 1, Step D. Purification of the resulting oil was carried out by filtration through a plug of silica gel (EtOAc as elu...
10.6084/m9.figshare.5104873.v1
null
Alkyne
null
null
null
c1ccccc1.c1ccccc1
null
[Pd].CCO
null
null
O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(C#CCCO)cc1F>[Pd].CCO>O=C(NOCCO)c1ccc(F)c(F)c1Nc1ccc(CCCCO)cc1F
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-96917a0bbab24ac9829bc12390da4106
CC(C)(O)C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1>>CC(C)(O)CCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)C#CC(C)(C)O)F>>FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)CCC(C)(C)O)F
[CH3:1][C:2]([CH3:3])([OH:4])[C:5]#[C:6][c:7]1[cH:8][cH:9][c:10]([NH:11][c:12]2[c:13]([C:14](=[O:15])[NH:16][O:17][CH2:18][CH2:19][OH:20])[cH:21][cH:22][c:23]([F:24])[c:25]2[F:26])[c:27]([F:28])[cH:29]1>>[CH3:1][C:2]([CH3:3])([OH:4])[CH2:5][CH2:6][c:7]1[cH:8][cH:9][c:10]([NH:11][c:12]2[c:13]([C:14](=[O:15])[NH:16][O:17...
CC(C)(O)C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
CC(C)(O)CCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
null
[Pd]
C(C)O
Reduction
OtherReaction
2bb8d5b532a2781e0a7c069a5cd3e8a7e8d44660c0ec1d9e17c04d8ba2cb383b
1990560e9c55934bde8ca0feaed9c61d80f37f94f0cf240a9929dc374d0a33aa
c1ccc(Nc2ccccc2)cc1
[C;D1;H3:1]-[C:2](-[C;D1;H3:3])(-[O;D1;H1:4])-[C;H0;D2;+0:5]#[C;H0;D2;+0:6]-[c:7](:[c:8]):[c:9]>>[C;D1;H3:1]-[C:2](-[C;D1;H3:3])(-[O;D1;H1:4])-[CH2;D2;+0:5]-[CH2;D2;+0:6]-[c:7](:[c:8]):[c:9]
99
[{"value": 99.0, "product": "FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)CCC(C)(C)O)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The product of Example 12, 3,4-difluoro-2-[2-fluoro-4-(3-hydroxy-3-methyl-1-butynyl)anilino]-N-(2-hydroxyethoxy)benzamide was hydrogenated in absolute ethanol in the presence of 5% Pd/C by the general procedure of Example 1, Step D. The resulting crude solid was purified by filtration through a plug of silica (MeOH as ...
10.6084/m9.figshare.5104873.v1
null
Alkyne
null
null
null
c1ccccc1.c1ccccc1
null
[Pd].C(C)O
null
null
CC(C)(O)C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1>[Pd].C(C)O>CC(C)(O)CCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-4595e47307364b58b48b58bd2015dbac
CCC(C)(O)C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1>>CCC(C)(O)CCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)C#CC(CC)(C)O)F>>FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)CCC(CC)(C)O)F
[CH3:1][CH2:2][C:3]([CH3:4])([OH:5])[C:6]#[C:7][c:8]1[cH:9][cH:10][c:11]([NH:12][c:13]2[c:14]([C:15](=[O:16])[NH:17][O:18][CH2:19][CH2:20][OH:21])[cH:22][cH:23][c:24]([F:25])[c:26]2[F:27])[c:28]([F:29])[cH:30]1>>[CH3:1][CH2:2][C:3]([CH3:4])([OH:5])[CH2:6][CH2:7][c:8]1[cH:9][cH:10][c:11]([NH:12][c:13]2[c:14]([C:15](=[O:...
CCC(C)(O)C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
CCC(C)(O)CCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
null
[Pd]
C(C)O
Reduction
OtherReaction
2bb8d5b532a2781e0a7c069a5cd3e8a7e8d44660c0ec1d9e17c04d8ba2cb383b
1990560e9c55934bde8ca0feaed9c61d80f37f94f0cf240a9929dc374d0a33aa
c1ccc(Nc2ccccc2)cc1
[C:1]-[C:2](-[C;D1;H3:3])(-[O;D1;H1:4])-[C;H0;D2;+0:5]#[C;H0;D2;+0:6]-[c:7](:[c:8]):[c:9]>>[C:1]-[C:2](-[C;D1;H3:3])(-[O;D1;H1:4])-[CH2;D2;+0:5]-[CH2;D2;+0:6]-[c:7](:[c:8]):[c:9]
98
[{"value": 98.0, "product": "FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)CCC(CC)(C)O)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The product of Example 13, 3,4-difluoro-2-[2-fluoro-4-(3-hydroxy-3-methyl-1-pentynyl)anilino]-N-(2-hydroxyethoxy)benzamide was hydrogenated in absolute ethanol in the presence of 5% Pd/C by the general procedure of Example 1, Step D. The resulting crude solid was purified by filtration through a plug of silica (MeOH as...
10.6084/m9.figshare.5104873.v1
null
Alkyne
null
null
null
c1ccccc1.c1ccccc1
null
[Pd].C(C)O
null
null
CCC(C)(O)C#Cc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1>[Pd].C(C)O>CCC(C)(O)CCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-c439634243f14a188004ab61d850db02
COCC#Cc1ccc(N)c(F)c1.O=C(O)c1ccc(F)c(F)c1F>>COCC#Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
FC1=C(C(=O)O)C=CC(=C1F)F.FC1=C(N)C=CC(=C1)C#CCOC.[Li+].C[Si](C)(C)[N-][Si](C)(C)C>>FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)C#CCOC)F
[CH3:1][O:2][CH2:3][C:4]#[C:5][c:6]1[cH:7][cH:8][c:9]([NH2:10])[c:22]([F:23])[cH:24]1.F[c:11]1[c:12]([C:13](=[O:14])[OH:15])[cH:16][cH:17][c:18]([F:19])[c:20]1[F:21]>>[CH3:1][O:2][CH2:3][C:4]#[C:5][c:6]1[cH:7][cH:8][c:9]([NH:10][c:11]2[c:12]([C:13](=[O:14])[OH:15])[cH:16][cH:17][c:18]([F:19])[c:20]2[F:21])[c:22]([F:23]...
COCC#Cc1ccc(N)c(F)c1.O=C(O)c1ccc(F)c(F)c1F
COCC#Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
da9dae6a655c4bd18887b692f91621e77027436294d6e1fc7be7295afb364796
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(Nc2ccccc2)cc1
F-[c;H0;D3;+0:1](:[c:2](-[C:3](=[O;D1;H0:4])-[O;D1;H1:5]):[c:6]):[c:7](-[F;D1;H0:8]):[c:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[F;D1;H0:8]-[c:7](:[c:9]):[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[c:2](-[C:3](=[O;D1;H0:4])-[O;D1;H1:5]):[c:6]
null
[]
null
null
null
null
2,3,4-Trifluorobenzoic acid and the product of Example 25, Step A, 2-fluoro-4-(3-methoxy-1-propynyl)aniline, were reacted in the presence of LiHMDS solution in THF by the general procedure of Example 1, Step B. After workup, followed by purification by chromatography on silica gel (10% EtOAc/hexanes as eluant), 3,4-dif...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HF
C1CCOC1
null
null
COCC#Cc1ccc(N)c(F)c1.O=C(O)c1ccc(F)c(F)c1F>C1CCOC1>COCC#Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a4eaf013c6c34739bc3f9746bb483624
COCC#Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1>>COCCCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)C#CCOC)F>>FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)CCCOC)F
[CH3:1][O:2][CH2:3][C:4]#[C:5][c:6]1[cH:7][cH:8][c:9]([NH:10][c:11]2[c:12]([C:13](=[O:14])[OH:15])[cH:16][cH:17][c:18]([F:19])[c:20]2[F:21])[c:22]([F:23])[cH:24]1>>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][c:6]1[cH:7][cH:8][c:9]([NH:10][c:11]2[c:12]([C:13](=[O:14])[OH:15])[cH:16][cH:17][c:18]([F:19])[c:20]2[F:21])[c:22]([F:23]...
COCC#Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
COCCCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
null
[Pd]
C(C)O
Reduction
OtherReaction
2bb8d5b532a2781e0a7c069a5cd3e8a7e8d44660c0ec1d9e17c04d8ba2cb383b
1990560e9c55934bde8ca0feaed9c61d80f37f94f0cf240a9929dc374d0a33aa
c1ccc(Nc2ccccc2)cc1
[#8:1]-[C:2]-[C;H0;D2;+0:3]#[C;H0;D2;+0:4]-[c:5](:[c:6]):[c:7]>>[#8:1]-[C:2]-[CH2;D2;+0:3]-[CH2;D2;+0:4]-[c:5](:[c:6]):[c:7]
65
[{"value": 65.0, "product": "FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)CCCOC)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The product of Example 25, Step B, 3,4-difluoro-2-[[2-fluoro-4-(3-methoxy-1-propynyl)phenyl]amino]benzoic acid, was hydrogenated in absolute ethanol in the presence of 5% Pd/C as above in Example 1, Step D. The resulting crude solid was purified by filtration through a plug of silica gel (50% EtOAc/hexanes as eluant) t...
10.6084/m9.figshare.5104873.v1
null
Alkyne
null
null
null
c1ccccc1.c1ccccc1
null
[Pd].C(C)O
null
null
COCC#Cc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1>[Pd].C(C)O>COCCCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-21ffa39c779d46b29f1fddda419cf3ee
COCCCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO>>COCCCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)CCCOC)F.C1=CN(C=N1)C(=O)N2C=CN=C2.NOCCO>>FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)CCCOC)F
O[C:13]([c:12]1[c:11]([NH:10][c:9]2[cH:8][cH:7][c:6]([CH2:5][CH2:4][CH2:3][O:2][CH3:1])[cH:28][c:26]2[F:27])[c:24]([F:25])[c:22]([F:23])[cH:21][cH:20]1)=[O:14].[NH2:15][O:16][CH2:17][CH2:18][OH:19]>>[CH3:1][O:2][CH2:3][CH2:4][CH2:5][c:6]1[cH:7][cH:8][c:9]([NH:10][c:11]2[c:12]([C:13](=[O:14])[NH:15][O:16][CH2:17][CH2:18...
COCCCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO
COCCCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
null
null
null
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
c1ccc(Nc2ccccc2)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C:6]-[#8:7]-[NH2;D1;+0:8]>>[C:6]-[#8:7]-[NH;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
69
[{"value": 69.0, "product": "FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)CCCOC)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was prepared from reaction of the product of Example 25, Step C, 3,4-difluoro-2-[[2-fluoro-4-(3-methoxypropyl)phenyl]amino]benzoic acid with CDI and 2-(aminooxy)ethanol, by the general procedure of Example 1, Step E, then purified by flash column chromatography on silica gel (50% EtOAc/hexanes) to gi...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccccc1.c1ccccc1
HO-
null
null
null
COCCCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO>>COCCCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3d5a5d07896b4feea0298b3cb0ee8fb8
N#C[S-].Nc1ccccc1F>>N#CSc1ccc(N)c(F)c1
C(=O)([O-])[O-].[Na+].[Na+].BrBr.FC1=C(N)C=CC=C1.[S-]C#N.[K+]>>NC1=C(C=C(C=C1)SC#N)F
[N:1]#[C:2][S-:3].[cH:4]1[cH:5][cH:6][c:7]([NH2:8])[c:9]([F:10])[cH:11]1>>[N:1]#[C:2][S:3][c:4]1[cH:5][cH:6][c:7]([NH2:8])[c:9]([F:10])[cH:11]1
N#C[S-].Nc1ccccc1F
N#CSc1ccc(N)c(F)c1
null
null
O.[Br-].[Na+].CO
Heteroatom Alkylation and Arylation
OtherReaction
29d483be92b78aea9894649c5ff004e9773d34416f95eeab1829acdbdeaacc59
21e67be598c63344ea1fea503581f1ce4855b092ed4079749b71ebb3b04166d6
c1ccccc1
[N;D1;H0:1]#[C:2]-[S-;H0;D1:3].[c:4]:[c:5]:[cH;D2;+0:6]:[c:7]:[c:8]>>[N;D1;H0:1]#[C:2]-[S;H0;D2;+0:3]-[c;H0;D3;+0:6](:[c:7]:[c:8]):[c:5]:[c:4]
53
[{"value": 53.0, "product": "NC1=C(C=C(C=C1)SC#N)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 52.8, "product": "NC1=C(C=C(C=C1)SC#N)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
0.5
HOUR
A solution of bromine (3.02 g, 18.9 mmol) in sodium bromide-saturated methanol (11 mL) was added dropwise to a solution of 2-fluoroaniline (2.00 g, 18.0 mmol) and potassium thiocyanate (5.25 g, 54.0 mmol) in methanol (45 mL). The mixture was stirred for 0.5 hours, at room temperature, poured into water (300 mL) and mad...
10.6084/m9.figshare.5104873.v1
null
null
Monosulfide
c1ccccc1
c1ccccc1
c1ccccc1
null
O.[Br-].[Na+].CO
null
0.5
N#C[S-].Nc1ccccc1F>O.[Br-].[Na+].CO>N#CSc1ccc(N)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-627d2afbdee44368942c36f3c6bcaed6
CI.N#CSc1ccc(N)c(F)c1>>CSc1ccc(N)c(F)c1
CI.NC1=C(C=C(C=C1)SC#N)F.NC1=C(C=C(C=C1)SC#N)F.O.[S-2].[Na+].[Na+]>>FC1=C(N)C=CC(=C1)SC
I[CH3:1].N#C[S:2][c:3]1[cH:4][cH:5][c:6]([NH2:7])[c:8]([F:9])[cH:10]1>>[CH3:1][S:2][c:3]1[cH:4][cH:5][c:6]([NH2:7])[c:8]([F:9])[cH:10]1
CI.N#CSc1ccc(N)c(F)c1
CSc1ccc(N)c(F)c1
null
null
O.C(C)O
Heteroatom Alkylation and Arylation
OtherReaction
814eda62f542c6c8a8489fc07e9c3a90fd7f13ede724ebe06dfb3edcf3916fdf
811ffad760b193ef7d543b0a95fb44c366861bf32d67304b457c7f95b7fc4f13
c1ccccc1
I-[CH3;D1;+0:1].N#C-[S;H0;D2;+0:2]-[c:3](:[c:4]):[c:5]>>[CH3;D1;+0:1]-[S;H0;D2;+0:2]-[c:3](:[c:4]):[c:5]
87
[{"value": 87.0, "product": "FC1=C(N)C=CC(=C1)SC", "details": "PERCENTYIELD", "is_desired": false}]
50
CELSIUS
4
HOUR
A solution of the product of Example 26, Step A, 4-amino-3-fluorophenyl thiocyanate (500 mg, 2.97 mmol), in ethanol (7.5 mL) was added to a solution of sodium sulfide monohydrate (714 mg, 2.97 mmol) in water (1.5 mL) and the mixture heated at 50° C. for 2 hours. Methyl iodide (464 mg, 3.27 mmol) in ethanol (0.5 mL) was...
10.6084/m9.figshare.5104873.v1
null
Nitrile.Monosulfide
Monosulfide
null
null
c1ccccc1
I-
O.C(C)O
50
4
CI.N#CSc1ccc(N)c(F)c1>O.C(C)O>CSc1ccc(N)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-32e71b0cf85c4ae48b219b6ae0e5c41b
CSc1ccc(N)c(F)c1.O=C(O)c1ccc(F)c(F)c1F>>CSc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
FC1=C(C(=O)O)C=CC(=C1F)F.FC1=C(N)C=CC(=C1)SC.FC1=C(N)C=CC(=C1)SC.[Li+].C[Si](C)(C)[N-][Si](C)(C)C>>FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)SC)F
[CH3:1][S:2][c:3]1[cH:4][cH:5][c:6]([NH2:7])[c:19]([F:20])[cH:21]1.F[c:8]1[c:9]([C:10](=[O:11])[OH:12])[cH:13][cH:14][c:15]([F:16])[c:17]1[F:18]>>[CH3:1][S:2][c:3]1[cH:4][cH:5][c:6]([NH:7][c:8]2[c:9]([C:10](=[O:11])[OH:12])[cH:13][cH:14][c:15]([F:16])[c:17]2[F:18])[c:19]([F:20])[cH:21]1
CSc1ccc(N)c(F)c1.O=C(O)c1ccc(F)c(F)c1F
CSc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
da9dae6a655c4bd18887b692f91621e77027436294d6e1fc7be7295afb364796
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(Nc2ccccc2)cc1
F-[c;H0;D3;+0:1](:[c:2](-[F;D1;H0:3]):[c:4]):[c:5](-[C:6](=[O;D1;H0:7])-[O;D1;H1:8]):[c:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[F;D1;H0:3]-[c:2](:[c:4]):[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[c:5](-[C:6](=[O;D1;H0:7])-[O;D1;H1:8]):[c:9]
52
[{"value": 52.0, "product": "FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)SC)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
2,3,4-Trifluorobenzoic acid and the product of Example 26, Step B, 2-fluoro-4-methylthioaniline, were reacted in the presence of LiHMDS solution in THF by the general procedure of Example 1, Step B. After workup, this material was purified by dry flash column chromatography on silica (0.5% Et2O in 1:1 CH2Cl2/hexanes as...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HF
C1CCOC1
null
null
CSc1ccc(N)c(F)c1.O=C(O)c1ccc(F)c(F)c1F>C1CCOC1>CSc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-32b5d7eabf2d45a28e6a0c51f337a23b
CSc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO>>CSc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)SC)F.C1=CN(C=N1)C(=O)N2C=CN=C2.NOCCO>>FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)SC)F
O[C:10]([c:9]1[c:8]([NH:7][c:6]2[cH:5][cH:4][c:3]([S:2][CH3:1])[cH:25][c:23]2[F:24])[c:21]([F:22])[c:19]([F:20])[cH:18][cH:17]1)=[O:11].[NH2:12][O:13][CH2:14][CH2:15][OH:16]>>[CH3:1][S:2][c:3]1[cH:4][cH:5][c:6]([NH:7][c:8]2[c:9]([C:10](=[O:11])[NH:12][O:13][CH2:14][CH2:15][OH:16])[cH:17][cH:18][c:19]([F:20])[c:21]2[F:2...
CSc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO
CSc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
null
null
null
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
c1ccc(Nc2ccccc2)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C:6]-[#8:7]-[NH2;D1;+0:8]>>[C:6]-[#8:7]-[NH;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
80
[{"value": 80.0, "product": "FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)SC)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was prepared from reaction of the product of Example 26, Step C, 3,4-difluoro-2-[[2-fluoro-4-(methylthio)phenyl]amino]benzoic acid, with CDI and 2-(aminooxy)ethanol by the general procedure of Example 1, Step E. Then, after workup, the crude solid triturated with Et2O and washed with pentane to affor...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccccc1.c1ccccc1
HO-
null
null
null
CSc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO>>CSc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-0951191161c74f289d2fe6513a0f5e04
CCI.N#CSc1ccc(N)c(F)c1>>CCSc1ccc(N)c(F)c1
C(C)I.NC1=C(C=C(C=C1)SC#N)F.NC1=C(C=C(C=C1)SC#N)F>>FC1=C(N)C=CC(=C1)SCC
I[CH2:2][CH3:1].N#C[S:3][c:4]1[cH:5][cH:6][c:7]([NH2:8])[c:9]([F:10])[cH:11]1>>[CH3:1][CH2:2][S:3][c:4]1[cH:5][cH:6][c:7]([NH2:8])[c:9]([F:10])[cH:11]1
CCI.N#CSc1ccc(N)c(F)c1
CCSc1ccc(N)c(F)c1
null
null
O.C(C)O
Heteroatom Alkylation and Arylation
OtherReaction
7a537837424ff035199d862c139991b73a0343ed1d8917ad14792f97a1d81ece
d9ceb7062b176f3e6428d11b6c9b4fb9a42d21fd0f34ba5ae00249f992efd6c5
c1ccccc1
I-[CH2;D2;+0:1]-[C;D1;H3:2].N#C-[S;H0;D2;+0:3]-[c:4](:[c:5]):[c:6]>>[C;D1;H3:2]-[CH2;D2;+0:1]-[S;H0;D2;+0:3]-[c:4](:[c:5]):[c:6]
92
[{"value": 92.0, "product": "FC1=C(N)C=CC(=C1)SCC", "details": "PERCENTYIELD", "is_desired": false}]
50
CELSIUS
1
HOUR
A solution of the product of Example 26, Step A, 4-amino-3-fluorophenyl thiocyanate (500 mg, 2.97 mmol), in ethanol (7 mL) was added dropwise to a solution of Na2S.9H2O (714 mg, 2.97 mmol) in water (1.5 mL) and the resulting mixture stirred at 50° C. for 1 hour. A solution of ethyl iodide (510 mg, 3.27 mmol) in ethanol...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Nitrile.Monosulfide
Monosulfide
null
null
c1ccccc1
I-
O.C(C)O
50
1
CCI.N#CSc1ccc(N)c(F)c1>O.C(C)O>CCSc1ccc(N)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-abfaeb570e064d149175c8c236dc2def
CCSc1ccc(N)c(F)c1.O=C(O)c1ccc(F)c(F)c1F>>CCSc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
FC1=C(C(=O)O)C=CC(=C1F)F.FC1=C(N)C=CC(=C1)SCC.FC1=C(N)C=CC(=C1)SCC.[Li+].C[Si](C)(C)[N-][Si](C)(C)C>>FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)SCC)F
[CH3:1][CH2:2][S:3][c:4]1[cH:5][cH:6][c:7]([NH2:8])[c:20]([F:21])[cH:22]1.F[c:9]1[c:10]([C:11](=[O:12])[OH:13])[cH:14][cH:15][c:16]([F:17])[c:18]1[F:19]>>[CH3:1][CH2:2][S:3][c:4]1[cH:5][cH:6][c:7]([NH:8][c:9]2[c:10]([C:11](=[O:12])[OH:13])[cH:14][cH:15][c:16]([F:17])[c:18]2[F:19])[c:20]([F:21])[cH:22]1
CCSc1ccc(N)c(F)c1.O=C(O)c1ccc(F)c(F)c1F
CCSc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
da9dae6a655c4bd18887b692f91621e77027436294d6e1fc7be7295afb364796
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(Nc2ccccc2)cc1
F-[c;H0;D3;+0:1](:[c:2](-[C:3](=[O;D1;H0:4])-[O;D1;H1:5]):[c:6]):[c:7](-[F;D1;H0:8]):[c:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[F;D1;H0:8]-[c:7](:[c:9]):[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[c:2](-[C:3](=[O;D1;H0:4])-[O;D1;H1:5]):[c:6]
55
[{"value": 55.0, "product": "FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)SCC)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
2,3,4-Trifluorobenzoic acid and the product of Example 27, Step A, 2-fluoro-4-ethylthioaniline, were reacted in the presence of LiHMDS solution in THF by the general procedure of Example 1, Step B. After workup, a yellow solid was obtained which was purified by dry flash column chromatography on silica (0.5% Et2O in 1:...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HF
C1CCOC1
null
null
CCSc1ccc(N)c(F)c1.O=C(O)c1ccc(F)c(F)c1F>C1CCOC1>CCSc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-cafa73904e494338b7ca5974bfa59ba8
CCSc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO>>CCSc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)SCC)F.C1=CN(C=N1)C(=O)N2C=CN=C2.NOCCO>>FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)SCC)F
O[C:11]([c:10]1[c:9]([NH:8][c:7]2[cH:6][cH:5][c:4]([S:3][CH2:2][CH3:1])[cH:26][c:24]2[F:25])[c:22]([F:23])[c:20]([F:21])[cH:19][cH:18]1)=[O:12].[NH2:13][O:14][CH2:15][CH2:16][OH:17]>>[CH3:1][CH2:2][S:3][c:4]1[cH:5][cH:6][c:7]([NH:8][c:9]2[c:10]([C:11](=[O:12])[NH:13][O:14][CH2:15][CH2:16][OH:17])[cH:18][cH:19][c:20]([F...
CCSc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO
CCSc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
null
null
null
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
c1ccc(Nc2ccccc2)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C:6]-[#8:7]-[NH2;D1;+0:8]>>[C:6]-[#8:7]-[NH;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
65
[{"value": 65.0, "product": "FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)SCC)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was prepared from reaction of the product of Example 27, Step B, 3,4-difluoro-2-[[2-fluoro-4-(ethylthio)phenyl]amino]benzoic acid with CDI and 2-(aminooxy)ethanol by the general procedure of Example 1, Step E. Then, after workup, the crude solid triturated with Et2O and washed with pentane to afford ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccccc1.c1ccccc1
HO-
null
null
null
CCSc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO>>CCSc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d1b37f0aa5984735a6aee631497d85bc
CS(=O)(=O)c1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO>>CS(=O)(=O)c1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
FC=1C(=C(C(=O)O)C=CC1F)NC1=C(C=C(C=C1)S(=O)(=O)C)F.C1=CN(C=N1)C(=O)N2C=CN=C2.NOCCO>>FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)S(=O)(=O)C)F
O[C:12]([c:11]1[c:10]([NH:9][c:8]2[cH:7][cH:6][c:5]([S:2]([CH3:1])(=[O:3])=[O:4])[cH:27][c:25]2[F:26])[c:23]([F:24])[c:21]([F:22])[cH:20][cH:19]1)=[O:13].[NH2:14][O:15][CH2:16][CH2:17][OH:18]>>[CH3:1][S:2](=[O:3])(=[O:4])[c:5]1[cH:6][cH:7][c:8]([NH:9][c:10]2[c:11]([C:12](=[O:13])[NH:14][O:15][CH2:16][CH2:17][OH:18])[cH...
CS(=O)(=O)c1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO
CS(=O)(=O)c1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
null
null
null
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
c1ccc(Nc2ccccc2)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C:6]-[#8:7]-[NH2;D1;+0:8]>>[C:6]-[#8:7]-[NH;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
52
[{"value": 52.0, "product": "FC=1C(=C(C(=O)NOCCO)C=CC1F)NC1=C(C=C(C=C1)S(=O)(=O)C)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was prepared from reaction of the product of Example 28, Step A, 3,4-difluoro-2-[[2-fluoro-4-(methylsulfonyl)phenyl]amino]benzoic acid, with CDI and 2-(aminooxy)ethanol by the general procedure of Example 1, Step E. Then, after workup, the crude solid purified by dry flash column chromatography on si...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccccc1.c1ccccc1
HO-
null
null
null
CS(=O)(=O)c1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO>>CS(=O)(=O)c1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a4c682bcb2c3452aabe8dcc2de953953
Nc1ccc(I)cc1F.[Li][CH2]CCC>>CCCCc1ccc(N)c(F)c1
[Li]CCCC.FC1=C(N)C=CC(=C1)I>>C(CCC)C1=CC(=C(N)C=C1)F
I[c:5]1[cH:6][cH:7][c:8]([NH2:9])[c:10]([F:11])[cH:12]1.[Li][CH2:4][CH2:3][CH2:2][CH3:1]>>[CH3:1][CH2:2][CH2:3][CH2:4][c:5]1[cH:6][cH:7][c:8]([NH2:9])[c:10]([F:11])[cH:12]1
Nc1ccc(I)cc1F.[Li][CH2]CCC
CCCCc1ccc(N)c(F)c1
null
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.[Cl-].[Cl-].[Zn+2]
C1CCOC1
C-C Coupling
Reaction of alkyl halides with organometallic coumpounds
0066f9b754d2f38fc3a3e00bd00efaa68e272a14d59eb48de899b8731ef9f439
191bc7600fa9483952eddd0040b2b21cf731d54d9c6629540e93105469ea07da
c1ccccc1
I-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5].[C:6]-[C:7]-[CH2;D2;+0:8]-[Li]>>[C:6]-[C:7]-[CH2;D2;+0:8]-[c;H0;D3;+0:1](:[c:2]:[c:3]):[c:4]:[c:5]
30
[{"value": 30.0, "product": "C(CCC)C1=CC(=C(N)C=C1)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 29.1, "product": "C(CCC)C1=CC(=C(N)C=C1)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
0
CELSIUS
15
MINUTE
ZnCl2 (5.17 g, 38.0 mmol) was weighed into a flask, which was then flame dried and flushed with N2. Anhydrous THF (20 ml) was then added at 0° C., followed by 2.5 M nBuLi (15.2 ml, 38.0 mmol). The reaction mixture was stirred at 0° C. for 15 min, after which 2-fluoro-4-iodoaniline (3.00 g, 12.7 mmol) in anhydrous THF (...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Alkyl lithium
null
c1ccccc1
c1ccccc1
c1ccccc1
I-.Li
C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.[Cl-].[Cl-].[Zn+2].C1CCOC1
0
0.25
Nc1ccc(I)cc1F.[Li][CH2]CCC>C=1C=CC(=CC1)[P](C=2C=CC=CC2)(C=3C=CC=CC3)[Pd]([P](C=4C=CC=CC4)(C=5C=CC=CC5)C=6C=CC=CC6)([P](C=7C=CC=CC7)(C=8C=CC=CC8)C=9C=CC=CC9)[P](C=1C=CC=CC1)(C=1C=CC=CC1)C=1C=CC=CC1.[Cl-].[Cl-].[Zn+2].C1CCOC1>CCCCc1ccc(N)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b6599587cad34dc3995cc971754ba0f6
CCCCc1ccc(N)c(F)c1.O=C(O)c1ccc(F)c(F)c1F>>CCCCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
FC1=C(C(=O)O)C=CC(=C1F)F.C(CCC)C1=CC(=C(N)C=C1)F.[Li+].C[Si](C)(C)[N-][Si](C)(C)C>>C(CCC)C1=CC(=C(NC2=C(C(=O)O)C=CC(=C2F)F)C=C1)F
[CH3:1][CH2:2][CH2:3][CH2:4][c:5]1[cH:6][cH:7][c:8]([NH2:9])[c:21]([F:22])[cH:23]1.F[c:10]1[c:11]([C:12](=[O:13])[OH:14])[cH:15][cH:16][c:17]([F:18])[c:19]1[F:20]>>[CH3:1][CH2:2][CH2:3][CH2:4][c:5]1[cH:6][cH:7][c:8]([NH:9][c:10]2[c:11]([C:12](=[O:13])[OH:14])[cH:15][cH:16][c:17]([F:18])[c:19]2[F:20])[c:21]([F:22])[cH:2...
CCCCc1ccc(N)c(F)c1.O=C(O)c1ccc(F)c(F)c1F
CCCCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
null
null
C1CCOC1
Heteroatom Alkylation and Arylation
Buchwald-Hartwig/Ullmann-Goldberg/N-arylation primary amine
da9dae6a655c4bd18887b692f91621e77027436294d6e1fc7be7295afb364796
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1ccc(Nc2ccccc2)cc1
F-[c;H0;D3;+0:1](:[c:2](-[C:3](=[O;D1;H0:4])-[O;D1;H1:5]):[c:6]):[c:7](-[F;D1;H0:8]):[c:9].[NH2;D1;+0:10]-[c:11](:[c:12]):[c:13]>>[F;D1;H0:8]-[c:7](:[c:9]):[c;H0;D3;+0:1](-[NH;D2;+0:10]-[c:11](:[c:12]):[c:13]):[c:2](-[C:3](=[O;D1;H0:4])-[O;D1;H1:5]):[c:6]
40
[{"value": 40.0, "product": "C(CCC)C1=CC(=C(NC2=C(C(=O)O)C=CC(=C2F)F)C=C1)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
2,3,4-Trifluorobenzoic acid and 4-butyl-2-fluoroaniline were reacted in the presence of LiHMDS solution in THF by the general procedure of Example 1, Step B, affording crude 2-(4-butyl-2-fluoroanilino)-3,4-difluorobenzoic acid after workup. The crude material was further purified by flash chromatography on silica (10% ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1ccccc1
c1ccccc1
c1ccccc1.c1ccccc1
HF
C1CCOC1
null
null
CCCCc1ccc(N)c(F)c1.O=C(O)c1ccc(F)c(F)c1F>C1CCOC1>CCCCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-6315cdb1a03b4202a2e59ded1d397c50
CCCCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO>>CCCCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
C(CCC)C1=CC(=C(NC2=C(C(=O)O)C=CC(=C2F)F)C=C1)F.C1=CN(C=N1)C(=O)N2C=CN=C2.NOCCO>>C(CCC)C1=CC(=C(NC2=C(C(=O)NOCCO)C=CC(=C2F)F)C=C1)F
O[C:12]([c:11]1[c:10]([NH:9][c:8]2[cH:7][cH:6][c:5]([CH2:4][CH2:3][CH2:2][CH3:1])[cH:27][c:25]2[F:26])[c:23]([F:24])[c:21]([F:22])[cH:20][cH:19]1)=[O:13].[NH2:14][O:15][CH2:16][CH2:17][OH:18]>>[CH3:1][CH2:2][CH2:3][CH2:4][c:5]1[cH:6][cH:7][c:8]([NH:9][c:10]2[c:11]([C:12](=[O:13])[NH:14][O:15][CH2:16][CH2:17][OH:18])[cH...
CCCCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO
CCCCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
null
null
null
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
c1ccc(Nc2ccccc2)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C:6]-[#8:7]-[NH2;D1;+0:8]>>[C:6]-[#8:7]-[NH;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
68
[{"value": 68.0, "product": "C(CCC)C1=CC(=C(NC2=C(C(=O)NOCCO)C=CC(=C2F)F)C=C1)F", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
The title compound was prepared from reaction of 2-(4-butyl-2-fluoroanilino)-3,4-difluorobenzoic acid with CDI and 2-(aminooxy)ethanol by the general procedure of Example 1, Step E, then purified by flash column chromatography on silica (50% EtOAc/Hexane as eluant) to give 2-(4-butyl-2-fluoroanilino)-3,4-difluoro-N-(2-...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccccc1.c1ccccc1
HO-
null
null
null
CCCCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1.NOCCO>>CCCCc1ccc(Nc2c(C(=O)NOCCO)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-34126a20ba3d4ddfa296dac0bad17c99
COC(C)(C)OC.COC(C)(C)OC.OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO>>CC1(C)OC[C@H]([C@@H](O)[C@H](O)[C@H]2COC(C)(C)O2)O1
C([O-])(O)=O.[Na+].C([C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO)O.O1CCCC1.COC(C)(C)OC.COC(C)(C)OC>>CC1(OC[C@@H](O1)[C@H]([C@@H]([C@H]2COC(O2)(C)C)O)O)C
CO[C:2](OC)([CH3:1])[CH3:3].CO[C:14](OC)([CH3:15])[CH3:16].[OH:4][CH2:5][C@H:6]([C@@H:7]([OH:8])[C@H:9]([OH:10])[C@@H:11]([CH2:12][OH:13])[OH:17])[OH:18]>>[CH3:1][C:2]1([CH3:3])[O:4][CH2:5][C@H:6]([C@@H:7]([OH:8])[C@H:9]([OH:10])[C@H:11]2[CH2:12][O:13][C:14]([CH3:15])([CH3:16])[O:17]2)[O:18]1
COC(C)(C)OC.COC(C)(C)OC.OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO
CC1(C)OC[C@H]([C@@H](O)[C@H](O)[C@H]2COC(C)(C)O2)O1
null
O.C1(=CC=C(C=C1)S(=O)(=O)O)C
CN(C=O)C
Heteroatom Alkylation and Arylation
OtherReaction
0831c7a204680ca83961aa9a34164020828b2a20dbbfc68e726a72ec22e7e46c
12d66e1e985804ee9752178b3b686e5b66d21e9126fae4c7a6d479ea827147a5
C1OC[C@H](CC[C@H]2COCO2)O1
C-O-[C;H0;D4;+0:1](-[C;D1;H3:2])(-[C;D1;H3:3])-O-C.C-O-[C;H0;D4;+0:4](-[C;D1;H3:5])(-[C;D1;H3:6])-O-C.[OH;D1;+0:7]-[C:8]-[C:9](-[OH;D1;+0:10])-[C:11]-[C:12]-[C:13](-[OH;D1;+0:14])-[C:15]-[OH;D1;+0:16]>>[C;D1;H3:5]-[C;H0;D4;+0:4]1(-[C;D1;H3:6])-[O;H0;D2;+0:7]-[C:8]-[C:9](-[C:11]-[C:12]-[C:13]2-[C:15]-[O;H0;D2;+0:16]-[C;...
47.3
[{"value": 47.3, "product": "CC1(OC[C@@H](O1)[C@H]([C@@H]([C@H]2COC(O2)(C)C)O)O)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
18
HOUR
To a stirring suspension of D-Mannitol (1.82 g, 10.0 mmol) in tetrahydrofuran (21 mL) and dimethylformamide (9 mL) was added p-toluenesulfonic acid monohydrate (0.02 g, 0.1 mmol,) at ambient temperature, followed by 2,2-dimethoxypropane (2.8 mL, 0.023 mol). The reaction mixture was stirred for 18 hours at room temperat...
10.6084/m9.figshare.5104873.v1
null
Ether.Ether.Ether.Ether.Primary alcohol.Primary alcohol.Secondary alcohol.Secondary alcohol
Ether.Ether.Ether.Ether
null
C1COCO1.C1COCO1
C1COCO1.C1COCO1
HO-
O.C1(=CC=C(C=C1)S(=O)(=O)O)C.CN(C=O)C
null
18
COC(C)(C)OC.COC(C)(C)OC.OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO>O.C1(=CC=C(C=C1)S(=O)(=O)O)C.CN(C=O)C>CC1(C)OC[C@H]([C@@H](O)[C@H](O)[C@H]2COC(C)(C)O2)O1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3b64bb33cef24f6e8fe907b906eadc38
CC1(C)OC[C@H](CO)O1.O=C1c2ccccc2C(=O)N1O>>CC1(C)OC[C@H](CON2C(=O)c3ccccc3C2=O)O1
CC1(OC[C@@H](O1)CO)C.ON1C(C=2C(C1=O)=CC=CC2)=O.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.N(=NC(=O)OCC)C(=O)OCC.CC1(OC[C@@H](O1)CO)C>>CC1(OC[C@@H](O1)CON1C(C2=CC=CC=C2C1=O)=O)C
O[CH2:7][C@H:6]1[CH2:5][O:4][C:2]([CH3:1])([CH3:3])[O:20]1.[OH:8][N:9]1[C:10](=[O:11])[c:12]2[cH:13][cH:14][cH:15][cH:16][c:17]2[C:18]1=[O:19]>>[CH3:1][C:2]1([CH3:3])[O:4][CH2:5][C@H:6]([CH2:7][O:8][N:9]2[C:10](=[O:11])[c:12]3[cH:13][cH:14][cH:15][cH:16][c:17]3[C:18]2=[O:19])[O:20]1
CC1(C)OC[C@H](CO)O1.O=C1c2ccccc2C(=O)N1O
CC1(C)OC[C@H](CON2C(=O)c3ccccc3C2=O)O1
null
null
O1CCCC1
Heteroatom Alkylation and Arylation
OtherReaction
0fcd381b777d6629b0c9e6356597dd7aaabef76c7dfe47721d8d10b5fc8adb37
2ab4024aa17b6e89368e6fe8ee731d32c7611cb9b23de403e301e8362fea90b1
O=C1c2ccccc2C(=O)N1OC[C@H]1COCO1
O-[CH2;D2;+0:1]-[C:2]1-[#8:3]-[C:4]-[#8:5]-[C:6]-1.[O;D1;H0:7]=[C:8]1-[c:9]:[c:10]-[C:11](=[O;D1;H0:12])-[#7:13]-1-[OH;D1;+0:14]>>[O;D1;H0:7]=[C:8]1-[c:9]:[c:10]-[C:11](=[O;D1;H0:12])-[#7:13]-1-[O;H0;D2;+0:14]-[CH2;D2;+0:1]-[C:2]1-[#8:3]-[C:4]-[#8:5]-[C:6]-1
97
[{"value": 97.0, "product": "CC1(OC[C@@H](O1)CON1C(C2=CC=CC=C2C1=O)=O)C", "details": "PERCENTYIELD", "is_desired": false}]
null
null
18
HOUR
A 3-L round-bottomed flask equipped with mechanical stirrer and additional funnel was charged with N-hydroxyphthalimide (68.0 g, 0.416 mol) and tetrahydrofuran (1.2 L) under nitrogen atmosphere. To this solution was added triphenylphosphine (109.2 g, 0.416 mol) and the product of Example 31, Step B, (S)-(2,2-dimethyl-[...
10.6084/m9.figshare.5104873.v1
null
Primary alcohol
null
null
null
C1COCO1.c1ccc2c(c1)C[NH]C2
HO-
O1CCCC1
null
18
CC1(C)OC[C@H](CO)O1.O=C1c2ccccc2C(=O)N1O>O1CCCC1>CC1(C)OC[C@H](CON2C(=O)c3ccccc3C2=O)O1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-8f5b4bb3d9eb4f009cf884288ecb6d46
CC1(C)OC[C@@H](CNO)O1.CCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1>>CCc1ccc(Nc2c(C(=O)NOC[C@H]3COC(C)(C)O3)ccc(F)c2F)c(F)c1
C(C)C1=CC(=C(C=C1)NC1=C(C(=O)O)C=CC(=C1F)F)F.CC1(OC[C@H](O1)CNO)C.CC1(OCC[C@@H](O1)CON)C.C(C)N(CC)CC.F[P-](F)(F)(F)(F)F.N1(N=NC2=C1C=CC=C2)O[P+](N2CCCC2)(N2CCCC2)N2CCCC2>>CC1(OC[C@@H](O1)CONC(C1=C(C(=C(C=C1)F)F)NC1=C(C=C(C=C1)CC)F)=O)C
[NH:12]([OH:13])[CH2:14][C@@H:15]1[CH2:16][O:17][C:18]([CH3:19])([CH3:20])[O:21]1.O[C:10]([c:9]1[c:8]([NH:7][c:6]2[cH:5][cH:4][c:3]([CH2:2][CH3:1])[cH:30][c:28]2[F:29])[c:26]([F:27])[c:24]([F:25])[cH:23][cH:22]1)=[O:11]>>[CH3:1][CH2:2][c:3]1[cH:4][cH:5][c:6]([NH:7][c:8]2[c:9]([C:10](=[O:11])[NH:12][O:13][CH2:14][C@H:15...
CC1(C)OC[C@@H](CNO)O1.CCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
CCc1ccc(Nc2c(C(=O)NOC[C@H]3COC(C)(C)O3)ccc(F)c2F)c(F)c1
null
null
ClCCl
Acylation
OtherReaction
5a5ff76e01d051a03a2c77088c884912413ce09f49ca50e186c0fb9c62ad0bd2
9b702924f2df230008ea1edd297d6a4305f6e78d7804dff7e838c4286e010bf9
O=C(NOC[C@H]1COCO1)c1ccccc1Nc1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[OH;D1;+0:6]-[NH;D2;+0:7]-[CH2;D2;+0:8]-[C:9]1-[#8:10]-[C:11]-[#8:12]-[C:13]-1>>[O;D1;H0:2]=[C;H0;D3;+0:1](-[NH;D2;+0:7]-[O;H0;D2;+0:6]-[CH2;D2;+0:8]-[C:9]1-[#8:10]-[C:11]-[#8:12]-[C:13]-1)-[c:3](:[c:4]):[c:5]
null
[]
null
null
90
MINUTE
To a stirring solution of the product of Example 1, Step D, 2-[(4-ethyl-2-fluorophenyl)amino]-3,4-difluorobenzoic acid (0.480 g, 1.626 mmol) in dichloromethane (25 mL) is added to the product of Example 31, Step D, (R)—O-(2,2-dimethyl-[1,3]dioxan-4-ylmethyl)-hydroxylamine (0.38 g, 2.57 mmol), triethylamine (0.54 mL, 3....
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Secondary amine
Secondary amide
null
null
c1ccccc1.C1COCO1.c1ccccc1
HO-
ClCCl
null
1.5
CC1(C)OC[C@@H](CNO)O1.CCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1>ClCCl>CCc1ccc(Nc2c(C(=O)NOC[C@H]3COC(C)(C)O3)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-7c280b71af1a4325818d2a3341d881cc
CCc1ccc(Nc2c(C(=O)NOC[C@H]3COC(C)(C)O3)ccc(F)c2F)c(F)c1>>CCc1ccc(Nc2c(C(=O)NOC[C@H](O)CO)ccc(F)c2F)c(F)c1
CC1(OC[C@@H](O1)CONC(C1=C(C(=C(C=C1)F)F)NC1=C(C=C(C=C1)CC)F)=O)C.C1(=CC=C(C=C1)S(=O)(=O)O)C>>O[C@@H](CONC(C1=C(C(=C(C=C1)F)F)NC1=C(C=C(C=C1)CC)F)=O)CO
CC1(C)[O:16][C@@H:15]([CH2:14][O:13][NH:12][C:10]([c:9]2[c:8]([NH:7][c:6]3[cH:5][cH:4][c:3]([CH2:2][CH3:1])[cH:27][c:25]3[F:26])[c:23]([F:24])[c:21]([F:22])[cH:20][cH:19]2)=[O:11])[CH2:17][O:18]1>>[CH3:1][CH2:2][c:3]1[cH:4][cH:5][c:6]([NH:7][c:8]2[c:9]([C:10](=[O:11])[NH:12][O:13][CH2:14][C@H:15]([OH:16])[CH2:17][OH:18...
CCc1ccc(Nc2c(C(=O)NOC[C@H]3COC(C)(C)O3)ccc(F)c2F)c(F)c1
CCc1ccc(Nc2c(C(=O)NOC[C@H](O)CO)ccc(F)c2F)c(F)c1
null
null
O.CO
Deprotection
Acetal hydrolysis to diol
5f7e1daa6b91d1ca6716348acae46f804565b19cb8bd8a05be2ed6c083743e87
d0de49ebcb43eafba55a762f6d5237c53d7a87b3a882d6753f793a17a3c3a120
c1ccc(Nc2ccccc2)cc1
C-C1(-C)-[O;H0;D2;+0:1]-[C:2](-[C:3])-[C:4]-[O;H0;D2;+0:5]-1>>[C:3]-[C:2](-[OH;D1;+0:1])-[C:4]-[OH;D1;+0:5]
94.4
[{"value": 94.4, "product": "O[C@@H](CONC(C1=C(C(=C(C=C1)F)F)NC1=C(C=C(C=C1)CC)F)=O)CO", "details": "PERCENTYIELD", "is_desired": false}, {"value": 94.4, "product": "O[C@@H](CONC(C1=C(C(=C(C=C1)F)F)NC1=C(C=C(C=C1)CC)F)=O)CO", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
17
HOUR
To a stirring solution of the product of Example 31, Step E, N-((R)-2,2-dimethyl-[1,3]dioxolan-4-ylmethoxy)-2-(4-ethyl-2-fluoro-phenylamino)-3,4-difluoro-benzamide (0.515 g, 1.213 mmol) in methanol (10 mL) and water (1 mL) was added p-toluenesulfonic acid (0.115 g, 0.607 mmol). After stirring for 17 hours the reaction ...
10.6084/m9.figshare.5104873.v1
null
Ether.Ether
Primary alcohol.Secondary alcohol
C1COCO1
null
c1ccccc1.c1ccccc1
Other
O.CO
null
17
CCc1ccc(Nc2c(C(=O)NOC[C@H]3COC(C)(C)O3)ccc(F)c2F)c(F)c1>O.CO>CCc1ccc(Nc2c(C(=O)NOC[C@H](O)CO)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-bc05ac99a34448169fb70c3de32d753e
O=C1O[C@H]([C@@H](O)CO)C(O)=C1O>>O=C1O[C@H]([C@@H](O)CO)[C@H](O)[C@@H]1O
O=C1C(O)=C(O)[C@H](O1)[C@@H](O)CO>>C([C@@H]([C@@H]1[C@@H]([C@@H](C(=O)O1)O)O)O)O
[O:1]=[C:2]1[O:3][C@H:4]([C@@H:5]([OH:6])[CH2:7][OH:8])[C:9]([OH:10])=[C:11]1[OH:12]>>[O:1]=[C:2]1[O:3][C@H:4]([C@@H:5]([OH:6])[CH2:7][OH:8])[C@H:9]([OH:10])[C@@H:11]1[OH:12]
O=C1O[C@H]([C@@H](O)CO)C(O)=C1O
O=C1O[C@H]([C@@H](O)CO)[C@H](O)[C@@H]1O
null
[Pd]
O
Reduction
Hydrogenation (double to single)
35bffc355da56b2729c3211f6da20eac560b68f89a9052680c16e18701c1de1e
f2f3dceb2fa4db8d2652a67eb089edbb1d41f08fc254b9c5ab3d7362315d197c
O=C1CCCO1
[C:1]-[C:2]1-[#8:3]-[C:4](=[O;D1;H0:5])-[C;H0;D3;+0:6](-[O;D1;H1:7])=[C;H0;D3;+0:8]-1-[O;D1;H1:9]>>[C:1]-[C:2]1-[#8:3]-[C:4](=[O;D1;H0:5])-[C@@H;D3;+0:6](-[O;D1;H1:7])-[C@H;D3;+0:8]-1-[O;D1;H1:9]
null
[]
null
null
2.5
DAY
To a solution of L-ascorbic acid in water is added Pd/C (10%). The mixture is subjected to hydrogenation in a Parr hydrogenator at 48 psi, 18° C. for about 2 to 3 days. The reaction mixture is filtered and the filtrate is concentrated in vacuo to afford L-gulonic γ-lactone, after drying at 50° C. in a vacuum oven for a...
10.6084/m9.figshare.5104873.v1
null
Ester.Enol.Enol
Ester.Secondary alcohol.Secondary alcohol
C1=CCOC1
C1CCOC1
C1CCOC1
null
[Pd].O
null
60
O=C1O[C@H]([C@@H](O)CO)C(O)=C1O>[Pd].O>O=C1O[C@H]([C@@H](O)CO)[C@H](O)[C@@H]1O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-9727f0de925b491185083a8b87351762
CC1(C)OC[C@@H]([C@H]2OC(=O)[C@@H](O)[C@H]2O)O1>>CC1(C)OC[C@@H](CO)O1
[OH-].[Na+].I(=O)(=O)(=O)[O-].[Na+].CC1(OC[C@H](O1)[C@@H]2[C@@H]([C@@H](C(=O)O2)O)O)C>>CC1(OC[C@H](O1)CO)C
O=C1[C@@H](O)[C@@H](O)[C@@H:7]([C@@H:6]2[CH2:5][O:4][C:2]([CH3:1])([CH3:3])[O:9]2)[O:8]1>>[CH3:1][C:2]1([CH3:3])[O:4][CH2:5][C@@H:6]([CH2:7][OH:8])[O:9]1
CC1(C)OC[C@@H]([C@H]2OC(=O)[C@@H](O)[C@H]2O)O1
CC1(C)OC[C@@H](CO)O1
null
null
O
Reduction
OtherReaction
6adaba872e9713768203b196c0cf2cb300b19c2d72944709c486be13cfa01fe8
8d479d153d636eb896155cd1db0f6fdb2f1c31c6d77c5d37d63519469c22f311
C1COCO1
O-[C@@H]1-C(=O)-[O;H0;D2;+0:1]-[C@H;D3;+0:2](-[C:3]2-[#8:4]-[C:5]-[#8:6]-[C:7]-2)-[C@@H]-1-O>>[OH;D1;+0:1]-[CH2;D2;+0:2]-[C:3]1-[#8:4]-[C:5]-[#8:6]-[C:7]-1
null
[]
null
null
2
HOUR
To a stirring suspension of the product of Example 32, Step B, 5,6-O-isopropylidene-L-gulono-1,4-lactone, in water is added solid sodium periodate in small portions at 3° C. to 5° C. The pH of the mixture is adjusted to 5.5 with 1N aqueous sodium hydroxide. The suspension is stirred for 2 hours at ambient temperature, ...
10.6084/m9.figshare.5104873.v1
null
Ester.Secondary alcohol.Secondary alcohol
Primary alcohol
C1CCOC1
null
C1COCO1
HO-
O
null
2
CC1(C)OC[C@@H]([C@H]2OC(=O)[C@@H](O)[C@H]2O)O1>O>CC1(C)OC[C@@H](CO)O1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b473736acb5643f9a894944ec78dad40
CC1(C)OCC(O)CO1.CCOC(=O)N=NC(=O)OCC.O=C1c2ccccc2C(=O)N1O.c1ccc(P(c2ccccc2)c2ccccc2)cc1>>CC1(C)OCC(O)CO1.CC1(C)OCC(ON2C(=O)c3ccccc3C2=O)CO1
CC1(OCC(CO1)O)C.ON1C(C=2C(C1=O)=CC=CC2)=O.C1(=CC=CC=C1)P(C1=CC=CC=C1)C1=CC=CC=C1.N(=NC(=O)OCC)C(=O)OCC>>CC1(OCC(CO1)O)C.CC1(OCC(CO1)ON1C(C2=CC=CC=C2C1=O)=O)C
[OH:7][CH:15]1[CH2:14][O:13][C:11]([CH3:10])([CH3:12])[O:29][CH2:28]1.CCO[C:6](=O)N=N[C:5]([O:4][CH2:2][CH3:1])=[O:9].[OH:16][N:17]1[C:18](=[O:19])[c:20]2[cH:21][cH:22][cH:23][cH:24][c:25]2[C:26]1=[O:27].c1ccc(P(c2ccccc2)c2[cH:3]ccc[cH:8]2)cc1>>[CH3:1][C:2]1([CH3:3])[O:4][CH2:5][CH:6]([OH:7])[CH2:8][O:9]1.[CH3:10][C:11...
CC1(C)OCC(O)CO1.CCOC(=O)N=NC(=O)OCC.O=C1c2ccccc2C(=O)N1O.c1ccc(P(c2ccccc2)c2ccccc2)cc1
CC1(C)OCC(O)CO1.CC1(C)OCC(ON2C(=O)c3ccccc3C2=O)CO1
null
null
O1CCCC1
Heteroatom Alkylation and Arylation
OtherReaction
cdb1b139b51253c38c7ac24540a762bcfaf4b35d0b6aac4cfd10cae406f48953
5bffd1bf565f92a8cda300ddd1a2f28d7a2dd65284aba9d48791cfd6639e680e
C1COCOC1.O=C1c2ccccc2C(=O)N1OC1COCOC1
C-C-O-[C;H0;D3;+0:1](=O)-N=N-[C;H0;D3;+0:2](=[O;H0;D1;+0:3])-[#8:4]-[CH2;D2;+0:5]-[C;D1;H3:6].[O;D1;H0:7]=[C:8]1-[c:9]:[c:10]-[C:11](=[O;D1;H0:12])-[#7:13]-1-[OH;D1;+0:14].[OH;D1;+0:15]-[CH;D3;+0:16]1-[C:17]-[#8:18]-[C:19]-[#8:20]-[C:21]-1.[cH;D2;+0:22]1:c:c:c:[cH;D2;+0:23]:c:1-P(-c1:c:c:c:c:c:1)-c1:c:c:c:c:c:1>>[C;D1;...
null
[]
null
null
3
HOUR
2,2-Dimethyl-[1,3]dioxan-5-ol was prepared as described previously (Forbes, D. C. et al.; Synthesis, 1998; 6:879–882). 1H NMR (400 MHz; DMSO-d6) δ 4.91 (d, 1H, J=5.1), 3.70–3.75 (m, 2 H), 3.41–3.46 (m, 3 H), 1.30 (s, 3 H), 1.24 (s, 3 H); MS (APCI+)=132.9. To a stirring solution of 2,2-dimethyl-[1,3]dioxan-5-ol (1.50 g,...
10.6084/m9.figshare.5104873.v1
null
Ether.Ether.Diazene.Secondary alcohol
Ether.Ether.Secondary alcohol
C1COCOC1.c1ccccc1.c1ccccc1.c1ccccc1
C1COCOC1.C1COCOC1
C1COCOC1.C1COCOC1.c1ccc2c(c1)C[NH]C2
HO-
O1CCCC1
null
3
CC1(C)OCC(O)CO1.CCOC(=O)N=NC(=O)OCC.O=C1c2ccccc2C(=O)N1O.c1ccc(P(c2ccccc2)c2ccccc2)cc1>O1CCCC1>CC1(C)OCC(O)CO1.CC1(C)OCC(ON2C(=O)c3ccccc3C2=O)CO1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-098cba35338843238638a834ddd05bba
CC1(C)OCC(ON2C(=O)c3ccccc3C2=O)CO1>>CC1(C)OCC(ON)CO1
CC1(OCC(CO1)ON1C(C2=CC=CC=C2C1=O)=O)C.CNN>>CC1(OCC(CO1)ON)C
O=C1c2ccccc2C(=O)[N:8]1[O:7][CH:6]1[CH2:5][O:4][C:2]([CH3:1])([CH3:3])[O:10][CH2:9]1>>[CH3:1][C:2]1([CH3:3])[O:4][CH2:5][CH:6]([O:7][NH2:8])[CH2:9][O:10]1
CC1(C)OCC(ON2C(=O)c3ccccc3C2=O)CO1
CC1(C)OCC(ON)CO1
null
null
ClCCl
Reduction
Phthalimide deprotection
8c6c904eae7a7d528fa3eeedb7e9706448ab9f7df249a16fa865a9210a6adc85
892f9aeb7d80035b81a0f5a363c9ed6a90780ba9faa3f0708093fa283b8c9a24
C1COCOC1
O=C1-[N;H0;D3;+0:1](-[#8:2]-[C:3])-C(=O)-c2:c:c:c:c:c:2-1>>[C:3]-[#8:2]-[NH2;D1;+0:1]
106.3
[{"value": 100.0, "product": "CC1(OCC(CO1)ON)C", "details": "PERCENTYIELD", "is_desired": false}, {"value": 106.3, "product": "CC1(OCC(CO1)ON)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
2
HOUR
To a stirring solution of the product of Example 33, Step A, 2-(2,2-dimethyl-[1,3]dioxan-5-yloxy)-isoindole-1,3-dione (1.72 g, 6.20 mmol), in dichloromethane (15 mL) at 0° C. under nitrogen was added methylhydrazine (0.36 mL, 6.82 mmol) and allowed to warm to room temperature. After stirring for 2 hours the reaction mi...
10.6084/m9.figshare.5104873.v1
null
Tertiary amide.Tertiary amide
Primary amine
c1ccc2c(c1)C[NH]C2
null
C1COCOC1
HO-
ClCCl
null
2
CC1(C)OCC(ON2C(=O)c3ccccc3C2=O)CO1>ClCCl>CC1(C)OCC(ON)CO1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a79ecd9c5da346269ed328d3e15ee622
CC1(C)OCC(ON)CO1.CCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1>>CCc1ccc(Nc2c(C(=O)NOC3COC(C)(C)OC3)ccc(F)c2F)c(F)c1
C(C)C1=CC(=C(C=C1)NC1=C(C(=O)O)C=CC(=C1F)F)F.CC1(OCC(CO1)ON)C.CC1(OCC(CO1)ON)C.C(C)N(CC)CC.F[P-](F)(F)(F)(F)F.N1(N=NC2=C1C=CC=C2)O[P+](N2CCCC2)(N2CCCC2)N2CCCC2>>CC1(OCC(CO1)ONC(C1=C(C(=C(C=C1)F)F)NC1=C(C=C(C=C1)CC)F)=O)C
[NH2:12][O:13][CH:14]1[CH2:15][O:16][C:17]([CH3:18])([CH3:19])[O:20][CH2:21]1.O[C:10]([c:9]1[c:8]([NH:7][c:6]2[cH:5][cH:4][c:3]([CH2:2][CH3:1])[cH:30][c:28]2[F:29])[c:26]([F:27])[c:24]([F:25])[cH:23][cH:22]1)=[O:11]>>[CH3:1][CH2:2][c:3]1[cH:4][cH:5][c:6]([NH:7][c:8]2[c:9]([C:10](=[O:11])[NH:12][O:13][CH:14]3[CH2:15][O:...
CC1(C)OCC(ON)CO1.CCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1
CCc1ccc(Nc2c(C(=O)NOC3COC(C)(C)OC3)ccc(F)c2F)c(F)c1
null
null
ClCCl
Acylation
Carboxylic acid with primary amine to amide
37494d655fc476b499cf056f6435518833ae87795aab58744c3c61cc6e2d35e8
1acc31e468ee9ff2d6601bea2d2eb10c464508bb7150073479303b3753dd92b4
O=C(NOC1COCOC1)c1ccccc1Nc1ccccc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5].[C:6]-[#8:7]-[NH2;D1;+0:8]>>[C:6]-[#8:7]-[NH;D2;+0:8]-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c:3](:[c:4]):[c:5]
61.4
[{"value": 61.4, "product": null, "details": "PERCENTYIELD", "is_desired": false}]
null
null
75
MINUTE
To a stirring solution of the product of Example 1, Step D, 2-[(4-ethyl-2-fluorophenyl)amino]-3,4-difluorobenzoic acid (0.480 g, 1.626 mmol) in dichloromethane (15 mL) is added the product of Example 33, Step B, O-(2,2-dimethyl-[1,3]dioxan-5-yl)-hydroxylamine (0.287 g, 1.951 mmol), triethylamine (0.41 mL, 2.927 mmol), ...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Primary amine
Secondary amide
null
null
c1ccccc1.C1COCOC1.c1ccccc1
HO-
ClCCl
null
1.25
CC1(C)OCC(ON)CO1.CCc1ccc(Nc2c(C(=O)O)ccc(F)c2F)c(F)c1>ClCCl>CCc1ccc(Nc2c(C(=O)NOC3COC(C)(C)OC3)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a7104acbbd12461a8b874be5fbda6497
CCc1ccc(Nc2c(C(=O)NOC3COC(C)(C)OC3)ccc(F)c2F)c(F)c1>>CCc1ccc(Nc2c(C(=O)NOC(CO)CO)ccc(F)c2F)c(F)c1
CC1(OCC(CO1)ONC(C1=C(C(=C(C=C1)F)F)NC1=C(C=C(C=C1)CC)F)=O)C.Cl>>C(C)C1=CC(=C(C=C1)NC1=C(C(=O)NOC(CO)CO)C=CC(=C1F)F)F
CC1(C)[O:16][CH2:15][CH:14]([O:13][NH:12][C:10]([c:9]2[c:8]([NH:7][c:6]3[cH:5][cH:4][c:3]([CH2:2][CH3:1])[cH:27][c:25]3[F:26])[c:23]([F:24])[c:21]([F:22])[cH:20][cH:19]2)=[O:11])[CH2:17][O:18]1>>[CH3:1][CH2:2][c:3]1[cH:4][cH:5][c:6]([NH:7][c:8]2[c:9]([C:10](=[O:11])[NH:12][O:13][CH:14]([CH2:15][OH:16])[CH2:17][OH:18])[...
CCc1ccc(Nc2c(C(=O)NOC3COC(C)(C)OC3)ccc(F)c2F)c(F)c1
CCc1ccc(Nc2c(C(=O)NOC(CO)CO)ccc(F)c2F)c(F)c1
null
null
C(C)O
Deprotection
Ether cleavage to primary alcohol
db60f3679fcc60468c35d46ab68797e1b8f177a1be5585affc59e7a3cf3777b0
2f23bf710218006c93ff728dc99485ec1b0a0e5cb41fb3252e62eb1ed984c4ac
c1ccc(Nc2ccccc2)cc1
C-C1(-C)-[O;H0;D2;+0:1]-[C:2]-[C:3]-[C:4]-[O;H0;D2;+0:5]-1>>[OH;D1;+0:1]-[C:2]-[C:3]-[C:4]-[OH;D1;+0:5]
84.6
[{"value": 84.6, "product": "C(C)C1=CC(=C(C=C1)NC1=C(C(=O)NOC(CO)CO)C=CC(=C1F)F)F", "details": "PERCENTYIELD", "is_desired": false}, {"value": 84.4, "product": "C(C)C1=CC(=C(C=C1)NC1=C(C(=O)NOC(CO)CO)C=CC(=C1F)F)F", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
To a stirring solution of the product of Example 33, Step C, N-(2,2-dimethyl-[1,3]dioxan-5-yloxy)-2-(4-ethyl-2-fluoro-phenylamino)-3,4-difluoro-benzamide (0.416 g, 0.980 mmol) in ethanol (5 mL) was added 1 molar aqueous hydrochloric acid solution (1 mL). After stirring for 1 hour at ambient temperature the reaction mix...
10.6084/m9.figshare.5104873.v1
null
Ether.Ether
Primary alcohol.Primary alcohol
C1COCOC1
null
c1ccccc1.c1ccccc1
Other
C(C)O
null
1
CCc1ccc(Nc2c(C(=O)NOC3COC(C)(C)OC3)ccc(F)c2F)c(F)c1>C(C)O>CCc1ccc(Nc2c(C(=O)NOC(CO)CO)ccc(F)c2F)c(F)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-7ccd6d335ce448838225837d6fa2e989
CCOC(=O)Oc1c2[nH]c3ccc(C(=O)OCC)cc3c2cc2c1[nH]c1ccc(C(=O)OCC)cc12.CCOC(=O)Oc1c2c(cc3c4cc(Br)ccc4n(C(=O)OC(C)(C)C)c13)c1cc(Br)ccc1n2C(=O)OC(C)(C)C>>CCOC(=O)Oc1c2c(cc3c1=Nc1ccc(C(=O)OCC)c(C(=O)OC(C)(C)C)c1-3)=c1cc(C(=O)OC(C)C(=O)OC(C)(C)C)ccc1=N2
[Li]C(C)(C)C.CCCCC.BrC=1C=C2C=3C=C4C(=C(C3N(C2=CC1)C(=O)OC(C)(C)C)OC(=O)OCC)N(C=1C=CC(=CC14)Br)C(=O)OC(C)(C)C.[NH4+].[Cl-].C(=O)(OCC)C=1C=C2C=3C=C4C(=C(C3NC2=CC1)OC(=O)OCC)NC=1C=CC(=CC14)C(=O)OCC.ClC(=O)OCC>>C(=O)(OC(C)(C)C)C1=C2C3=CC=4C(=C(C3=NC2=CC=C1C(=O)OCC)OC(=O)OCC)N=C1C=CC(=CC14)C(=O)OC(C)C(=O)OC(C)(C)C
CCOC(=O)Oc1c2[nH]c3ccc([C:18](=[O:19])[O:20][CH2:21][CH3:22])cc3c2cc2c1[nH]c1ccc([C:35](=[O:36])[O:37][CH2:38][CH3:39])cc12.Br[c:17]1[cH:16][cH:15][c:14]2[n:13]([C:24](=[O:25])[O:26][C:27]([CH3:28])([CH3:29])[CH3:30])[c:12]3[c:7]([O:6][C:4]([O:3][CH2:2][CH3:1])=[O:5])[c:8]4[c:9]([cH:10][c:11]3[c:31]2[cH:23]1)[c:32]1[cH...
CCOC(=O)Oc1c2[nH]c3ccc(C(=O)OCC)cc3c2cc2c1[nH]c1ccc(C(=O)OCC)cc12.CCOC(=O)Oc1c2c(cc3c4cc(Br)ccc4n(C(=O)OC(C)(C)C)c13)c1cc(Br)ccc1n2C(=O)OC(C)(C)C
CCOC(=O)Oc1c2c(cc3c1=Nc1ccc(C(=O)OCC)c(C(=O)OC(C)(C)C)c1-3)=c1cc(C(=O)OC(C)C(=O)OC(C)(C)C)ccc1=N2
null
null
CCOC(=O)C.CCCCCC.C1CCOC1
C-C Coupling
OtherReaction
d354052b5a19e91e3692a64042437acc2acc1c94e80c9a5e8ef7c022611012ac
78d8ffa0c4678aa2c77d69612c39175aa3885ae8e5b78b421fcfc250fa0c0671
c1ccc2c(c1)N=c1cc3c(cc1-2)=c1ccccc1=N3
Br-[c;H0;D3;+0:1]1:[c:2]:[c:3]:[c:4]2:[c;H0;D3;+0:5](:[cH;D2;+0:6]:1):[c;H0;D3;+0:7]1:[c:8]:[c;H0;D3;+0:9]3:[c:10](:[c:11](-[#8:12]-[C:13]=[O;D1;H0:14]):[c;H0;D3;+0:15]:1:[n;H0;D3;+0:16]:2-[C;H0;D3;+0:17](=[O;D1;H0:18])-[#8:19]-[C:20](-[C;D1;H3:21])(-[C;D1;H3:22])-[C;D1;H3:23]):[n;H0;D3;+0:24](-[C;H0;D3;+0:25](=[O;D1;H...
89
[{"value": 89.0, "product": "C(=O)(OC(C)(C)C)C1=C2C3=CC=4C(=C(C3=NC2=CC=C1C(=O)OCC)OC(=O)OCC)N=C1C=CC(=CC14)C(=O)OC(C)C(=O)OC(C)(C)C", "details": "PERCENTYIELD", "is_desired": false}]
-10
CELSIUS
10
MINUTE
2,10-Dicarbethoxy-6-ethoxycarbonyloxy-5,7-dihydro-indolo [2,3-b]carbazole (63). To a solution of 1.7 M t-BuLi in pentane (32.3 mL, 54.8 mmol) in THF (200 mL) at −100° C. under argon was added 61 (7.0 g, 9.97 mmol) in THF (20 mL), and stirred for 10 min. ClCO2CH2CH3 (30 mL) was added and the mixture was slowly warmed to...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Aromatic halide.Ester.Ester.Ether.Ether.Ether.Ether.Boc.Boc
Ester.Ester.Ester.Ester.Boc.Boc
c1ccc2c(c1)nc1cc3nc4ccccc4c3cc12.c1ccc2c(c1)N=c1cc3c(cc12)c1ccccc1=N3
c1ccc2c(c1)N=c1cc3c(cc12)c1ccccc1=N3
c1ccc2c(c1)N=c1cc3c(cc12)c1ccccc1=N3
HBr
CCOC(=O)C.CCCCCC.C1CCOC1
-10
0.166667
CCOC(=O)Oc1c2[nH]c3ccc(C(=O)OCC)cc3c2cc2c1[nH]c1ccc(C(=O)OCC)cc12.CCOC(=O)Oc1c2c(cc3c4cc(Br)ccc4n(C(=O)OC(C)(C)C)c13)c1cc(Br)ccc1n2C(=O)OC(C)(C)C>CCOC(=O)C.CCCCCC.C1CCOC1>CCOC(=O)Oc1c2c(cc3c1=Nc1ccc(C(=O)OCC)c(C(=O)OC(C)(C)C)c1-3)=c1cc(C(=O)OC(C)C(=O)OC(C)(C)C)ccc1=N2
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3672edfb92dc40a3a074c125d9de4add
CCC(=O)C(Cl)C(=O)OC.Nc1nccnc1Cl>>CCc1nc2c(Cl)nccn2c1C(=O)OC
ClC=1C(=NC=CN1)N.ClC(C(=O)OC)C(CC)=O>>COC(=O)C1=C(N=C2N1C=CN=C2Cl)CC
O=[C:3]([CH2:2][CH3:1])[CH:12](Cl)[C:13](=[O:14])[O:15][CH3:16].[NH2:4][c:5]1[c:6]([Cl:7])[n:8][cH:9][cH:10][n:11]1>>[CH3:1][CH2:2][c:3]1[n:4][c:5]2[c:6]([Cl:7])[n:8][cH:9][cH:10][n:11]2[c:12]1[C:13](=[O:14])[O:15][CH3:16]
CCC(=O)C(Cl)C(=O)OC.Nc1nccnc1Cl
CCc1nc2c(Cl)nccn2c1C(=O)OC
null
null
null
Aromatic Heterocycle Formation
OtherReaction
9ef3f8c7d8012f16862df6e6d5d64f5e5c28836502935c9f0f51594189d35521
31aa25659cf5accd41f8ff85a49e4d2b829110bf1926ff7161f2261cc71e0db2
c1cn2ccnc2cn1
Cl-[CH;D3;+0:1](-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5])-[C;H0;D3;+0:6](=O)-[C:7]-[C;D1;H3:8].[Cl;D1;H0:9]-[c:10]1:[#7;a:11]:[c:12]:[c:13]:[n;H0;D2;+0:14]:[c:15]:1-[NH2;D1;+0:16]>>[C;D1;H3:5]-[#8:4]-[C:2](=[O;D1;H0:3])-[c;H0;D3;+0:1]1:[c;H0;D3;+0:6](-[C:7]-[C;D1;H3:8]):[n;H0;D2;+0:16]:[c:15]2:[c:10](-[Cl;D1;H0:9]):[#7;...
25.5
[{"value": 25.5, "product": "COC(=O)C1=C(N=C2N1C=CN=C2Cl)CC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
170
CELSIUS
2
HOUR
3-Chloro-2-aminopyrazine (2.1 g, 16.2 mmol) and methyl 2-chloro-3-oxopentanoate (6.7 mL, 48.6 mmol) were mixed, and heated under stirring at 170° C. for 2 hours. After being allowed to cool, the unnecessary materials were filtered off and washed with ethyl acetate, and then filtrates were combined and evaporated. The r...
10.6084/m9.figshare.5104873.v1
null
Secondary halide.Ketone.Ester.Primary amine
Ester
c1cnccn1
c1cn2ccnc2cn1
c1cn2ccnc2cn1
HCl
null
170
2
CCC(=O)C(Cl)C(=O)OC.Nc1nccnc1Cl>>CCc1nc2c(Cl)nccn2c1C(=O)OC
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-af52f131170f4f0b925451eb64c45d74
Nc1nccnc1-c1ccc(Cl)cc1Cl.O=C1CCC(=O)N1Cl>>Nc1ncc(Cl)nc1-c1ccc(Cl)cc1Cl
ClC1=C(C=CC(=C1)Cl)C=1C(=NC=CN1)N.ClN1C(CCC1=O)=O.O>>ClC=1N=C(C(=NC1)N)C1=C(C=C(C=C1)Cl)Cl
[NH2:1][c:2]1[n:3][cH:4][cH:5][n:7][c:8]1-[c:9]1[cH:10][cH:11][c:12]([Cl:13])[cH:14][c:15]1[Cl:16].O=C1CCC(=O)N1[Cl:6]>>[NH2:1][c:2]1[n:3][cH:4][c:5]([Cl:6])[n:7][c:8]1-[c:9]1[cH:10][cH:11][c:12]([Cl:13])[cH:14][c:15]1[Cl:16]
Nc1nccnc1-c1ccc(Cl)cc1Cl.O=C1CCC(=O)N1Cl
Nc1ncc(Cl)nc1-c1ccc(Cl)cc1Cl
null
null
C(Cl)(Cl)Cl
Functional Group Interconversion
Chlorination
bc1f7cfdae813ebe8c69faae7323293eaef048ef481216eb2be3204f184b46ec
0e444576b73669992a4073cc3f7b10ed52cb9df09f9f8e4042e39e6a602aa390
c1ccc(-c2cnccn2)cc1
O=C1-C-C-C(=O)-N-1-[Cl;H0;D1;+0:1].[#7;a:2]1:[c:3]:[c:4]:[#7;a:5]:[cH;D2;+0:6]:[c:7]:1>>[Cl;H0;D1;+0:1]-[c;H0;D3;+0:6]1:[#7;a:5]:[c:4]:[c:3]:[#7;a:2]:[c:7]:1
93.5
[{"value": 93.5, "product": "ClC=1N=C(C(=NC1)N)C1=C(C=C(C=C1)Cl)Cl", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
3-(2,4-Dichlorophenyl)-2-pyrazinamine (1.43 g, 6.0 mmol) was dissolved in chloroform (9 mL), N-chlorosuccinimide (0.96 g, 7.2 mmol) was added thereto, and the mixture was stirred by heating under reflux for 4 hours. After being allowed to cool, water was added to the reaction mixture, which was extracted with ethyl ace...
10.6084/m9.figshare.5104873.v1
null
Tertiary amide.Tertiary amide
Aromatic halide
c1cnccn1.C1CCNC1
c1cnccn1
c1cnccn1.c1ccccc1
HO-
C(Cl)(Cl)Cl
null
null
Nc1nccnc1-c1ccc(Cl)cc1Cl.O=C1CCC(=O)N1Cl>C(Cl)(Cl)Cl>Nc1ncc(Cl)nc1-c1ccc(Cl)cc1Cl
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-4f8d44ee9da14af286866a53df2b00c2
CCC(=O)C(Cl)C(=O)OC.Cc1cnc(N)c(Br)n1>>CCc1nc2c(Br)nc(C)cn2c1C(=O)OC
BrC=1C(=NC=C(N1)C)N.ClC(C(=O)OC)C(CC)=O>>COC(=O)C1=C(N=C2N1C=C(N=C2Br)C)CC
O=[C:3]([CH2:2][CH3:1])[CH:13](Cl)[C:14](=[O:15])[O:16][CH3:17].[NH2:4][c:5]1[c:6]([Br:7])[n:8][c:9]([CH3:10])[cH:11][n:12]1>>[CH3:1][CH2:2][c:3]1[n:4][c:5]2[c:6]([Br:7])[n:8][c:9]([CH3:10])[cH:11][n:12]2[c:13]1[C:14](=[O:15])[O:16][CH3:17]
CCC(=O)C(Cl)C(=O)OC.Cc1cnc(N)c(Br)n1
CCc1nc2c(Br)nc(C)cn2c1C(=O)OC
null
null
null
Aromatic Heterocycle Formation
OtherReaction
9ef3f8c7d8012f16862df6e6d5d64f5e5c28836502935c9f0f51594189d35521
31aa25659cf5accd41f8ff85a49e4d2b829110bf1926ff7161f2261cc71e0db2
c1cn2ccnc2cn1
Cl-[CH;D3;+0:1](-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5])-[C;H0;D3;+0:6](=O)-[C:7]-[C;D1;H3:8].[Br;D1;H0:9]-[c:10]1:[#7;a:11]:[c:12](-[C;D1;H3:13]):[c:14]:[n;H0;D2;+0:15]:[c:16]:1-[NH2;D1;+0:17]>>[Br;D1;H0:9]-[c:10]1:[#7;a:11]:[c:12](-[C;D1;H3:13]):[c:14]:[n;H0;D3;+0:15]2:[c:16]:1:[n;H0;D2;+0:17]:[c;H0;D3;+0:6](-[C:7]-[...
5.8
[{"value": 5.8, "product": "COC(=O)C1=C(N=C2N1C=C(N=C2Br)C)CC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
130
CELSIUS
1
HOUR
3-Bromo-5-methyl-2-pyrazineamine (3.5 g, 18.6 mmol) and methyl 2-chloro-3-oxopentanoate (6.7 mL, 48.6 mmol) were mixed, and the mixture was heated under stirring at 130° C. for 1 hour. After being allowed to cool, the unnecessary materials were filtered off and washed with ethyl acetate, and then the filtrates were com...
10.6084/m9.figshare.5104873.v1
null
Secondary halide.Ketone.Ester.Primary amine
Ester
c1cnccn1
c1cn2ccnc2cn1
c1cn2ccnc2cn1
HCl
null
130
1
CCC(=O)C(Cl)C(=O)OC.Cc1cnc(N)c(Br)n1>>CCc1nc2c(Br)nc(C)cn2c1C(=O)OC
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e51d2344008247c5826386b93d8b5392
CCc1cn2ccnc(Cl)c2n1.CN(C)C=O>>CCc1nc2c(Cl)nccn2c1C=O
ClC=1C=2N(C=CN1)C=C(N2)CC.CN(C=O)C.P(=O)(Cl)(Cl)Cl>>ClC=1C=2N(C=CN1)C(=C(N2)CC)C=O
[CH3:1][CH2:2][c:3]1[n:4][c:5]2[c:6]([Cl:7])[n:8][cH:9][cH:10][n:11]2[cH:12]1.CN(C)[CH:13]=[O:14]>>[CH3:1][CH2:2][c:3]1[n:4][c:5]2[c:6]([Cl:7])[n:8][cH:9][cH:10][n:11]2[c:12]1[CH:13]=[O:14]
CCc1cn2ccnc(Cl)c2n1.CN(C)C=O
CCc1nc2c(Cl)nccn2c1C=O
null
null
null
C-C Coupling
OtherReaction
e72235189db37a417e31189cefe09560ddeac4330840d64763923712813d11ed
f0bd75a0630092c31f21f61f4a015c77ae0dff14a0b742b4370d7a38fda490f7
c1cn2ccnc2cn1
C-N(-C)-[CH;D2;+0:1]=[O;D1;H0:2].[C:3]-[c:4]1:[#7;a:5]:[c:6]2:[c:7]:[#7;a:8]:[c:9]:[c:10]:[#7;a:11]:2:[cH;D2;+0:12]:1>>[C:3]-[c:4]1:[#7;a:5]:[c:6]2:[c:7]:[#7;a:8]:[c:9]:[c:10]:[#7;a:11]:2:[c;H0;D3;+0:12]:1-[CH;D2;+0:1]=[O;D1;H0:2]
null
[]
90
CELSIUS
2
HOUR
8-Chloro-2-ethylimidazo[1,2-a]pyrazine (600 mg, 3.3 mmol) was dissolved in N,N-dimethylformamide (3.3 mL), phosphorus oxychloride (1.2 mL, 13.2 mmol) was added dropwise at room temperature, and the mixture was heated under stirring at 90° C. for 2 hours. After being allowed to cool, the reaction mixture was poured into...
10.6084/m9.figshare.5104873.v1
null
Tertiary amide
Aldehyde
c1cn2ccnc2cn1
c1cn2ccnc2cn1
c1cn2ccnc2cn1
Other
null
90
2
CCc1cn2ccnc(Cl)c2n1.CN(C)C=O>>CCc1nc2c(Cl)nccn2c1C=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-f7cbd6c8b578408b9693bca3dfa726d9
CCCC(O)c1c(CC)nc2c(Cl)nccn12.CCI>>CCCC(OCC)c1c(CC)nc2c(Cl)nccn12
O.ICC.[H-].[Na+].ClC=1C=2N(C=CN1)C(=C(N2)CC)C(CCC)O>>C(C)OC(CCC)C1=C(N=C2N1C=CN=C2Cl)CC
[CH3:1][CH2:2][CH2:3][CH:4]([OH:5])[c:8]1[c:9]([CH2:10][CH3:11])[n:12][c:13]2[c:14]([Cl:15])[n:16][cH:17][cH:18][n:19]12.I[CH2:6][CH3:7]>>[CH3:1][CH2:2][CH2:3][CH:4]([O:5][CH2:6][CH3:7])[c:8]1[c:9]([CH2:10][CH3:11])[n:12][c:13]2[c:14]([Cl:15])[n:16][cH:17][cH:18][n:19]12
CCCC(O)c1c(CC)nc2c(Cl)nccn12.CCI
CCCC(OCC)c1c(CC)nc2c(Cl)nccn12
null
null
CN(C=O)C
Heteroatom Alkylation and Arylation
Williamson Ether Synthesis
2e63de7b1f097c059f31781c5dec3b7812b761a1b3812b5238753f554cfa0846
9d3e82e8fa4f4bc62c1019e0bd869bdb0cf4748977f3c0b945b8ffdfc70126be
c1cn2ccnc2cn1
I-[CH2;D2;+0:1]-[C;D1;H3:2].[#7;a:3]:[c:4]:[c:5](-[C:6](-[C:7])-[OH;D1;+0:8]):[#7;a:9]>>[#7;a:3]:[c:4]:[c:5](-[C:6](-[C:7])-[O;H0;D2;+0:8]-[CH2;D2;+0:1]-[C;D1;H3:2]):[#7;a:9]
null
[]
null
null
3
HOUR
The resulting 1-(8-chloro-2-ethylimidazo[1,2-a]pyrazin-3-yl)-1-butanol was dissolved in N,N-dimethylformamide (2.2 mL), then iodoethane (0.079 mL, 0.99 mmol) and sodium hydride (65% in oil; 49 mg, 1.32 mmol) were added thereto under ice-cooling, and the mixture was stirred for 3 hours. Water was added to the reaction m...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Secondary alcohol
Ether
null
null
c1cn2ccnc2cn1
HI
CN(C=O)C
null
3
CCCC(O)c1c(CC)nc2c(Cl)nccn12.CCI>CN(C=O)C>CCCC(OCC)c1c(CC)nc2c(Cl)nccn12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-72159f0f66b74005a17e9d77b719b034
CCCC(O)c1c(CC)nc2c(Cl)nccn12>>CCCC(=O)c1c(CC)nc2c(Cl)nccn12
ClC=1C=2N(C=CN1)C(=C(N2)CC)C(CCC)O>>ClC=1C=2N(C=CN1)C(=C(N2)CC)C(CCC)=O
[CH3:1][CH2:2][CH2:3][CH:4]([OH:5])[c:6]1[c:7]([CH2:8][CH3:9])[n:10][c:11]2[c:12]([Cl:13])[n:14][cH:15][cH:16][n:17]12>>[CH3:1][CH2:2][CH2:3][C:4](=[O:5])[c:6]1[c:7]([CH2:8][CH3:9])[n:10][c:11]2[c:12]([Cl:13])[n:14][cH:15][cH:16][n:17]12
CCCC(O)c1c(CC)nc2c(Cl)nccn12
CCCC(=O)c1c(CC)nc2c(Cl)nccn12
null
[O-2].[Mn+4].[O-2]
C(Cl)Cl.C(C)(=O)OCC
Oxidation
Oxidation or Dehydrogenation of Alcohols to Aldehydes and Ketones
c7c20d2959ac48847b03cc1265962cf99a8ec8a85900c087dabb30077298c66c
767cfd93f5821ebb9e1e72addd9cb404b20b0c821d246ae6b87a5776b74a455b
c1cn2ccnc2cn1
[C:1]-[C:2]-[CH;D3;+0:3](-[OH;D1;+0:4])-[c:5]1:[#7;a:6]2:[c:7]:[c:8]:[#7;a:9]:[c:10]:[c:11]:2:[#7;a:12]:[c:13]:1-[C:14]>>[C:1]-[C:2]-[C;H0;D3;+0:3](=[O;H0;D1;+0:4])-[c:5]1:[#7;a:6]2:[c:7]:[c:8]:[#7;a:9]:[c:10]:[c:11]:2:[#7;a:12]:[c:13]:1-[C:14]
null
[]
60
CELSIUS
5
HOUR
The resulting 1-(8-chloro-2-ethylimidazo[1,2-a]pyrazin-3-yl)-1-butanol was dissolved in ethyl acetate (4 mL) and methylene chloride (1 mL), then activated manganese (IV) oxide (3 g) was added thereto, and the mixture was heated under stirring at 60° C. for 5 hours. After being allowed to cool, the reaction mixture was ...
10.6084/m9.figshare.5104873.v1
null
Secondary alcohol
Ketone
null
null
c1cn2ccnc2cn1
null
[O-2].[Mn+4].[O-2].C(Cl)Cl.C(C)(=O)OCC
60
5
CCCC(O)c1c(CC)nc2c(Cl)nccn12>[O-2].[Mn+4].[O-2].C(Cl)Cl.C(C)(=O)OCC>CCCC(=O)c1c(CC)nc2c(Cl)nccn12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-a208b4e824e9469ab599b6b4e775f6d6
CC(=O)/C=C/c1ccc(C)cc1C.[C-]#N>>CC(=O)CC(C#N)c1ccc(C)cc1C
[Cl-].[NH4+].[C-]#N.[K+].CC1=C(C=CC(=C1)C)/C=C/C(C)=O.CN(C=O)C>>CC1=C(C=CC(=C1)C)C(CC(C)=O)C#N
[CH3:1][C:2](=[O:3])/[CH:4]=[CH:5]/[c:8]1[cH:9][cH:10][c:11]([CH3:12])[cH:13][c:14]1[CH3:15].[C-:6]#[N:7]>>[CH3:1][C:2](=[O:3])[CH2:4][CH:5]([C:6]#[N:7])[c:8]1[cH:9][cH:10][c:11]([CH3:12])[cH:13][c:14]1[CH3:15]
CC(=O)/C=C/c1ccc(C)cc1C.[C-]#N
CC(=O)CC(C#N)c1ccc(C)cc1C
null
null
O
C-C Coupling
OtherReaction
876100d9029380276bad4bfffd336e941029e62a60aedd8b2e7be808cdf4dbf7
491da00d5858e1f2efb2cb52ad5e0bdc63f42de65d8d378a501175351ff676a5
c1ccccc1
[C-;H0;D1:1]#[N;D1;H0:2].[C;D1;H3:3]-[C:4](=[O;D1;H0:5])/[CH;D2;+0:6]=[CH;D2;+0:7]/[c:8](:[c:9]):[c:10]>>[C;D1;H3:3]-[C:4](=[O;D1;H0:5])-[CH2;D2;+0:6]-[CH;D3;+0:7](-[C;H0;D2;+0:1]#[N;D1;H0:2])-[c:8](:[c:9]):[c:10]
48
[{"value": 48.0, "product": "CC1=C(C=CC(=C1)C)C(CC(C)=O)C#N", "details": "PERCENTYIELD", "is_desired": false}]
null
null
null
null
Ammonium chloride (6.84 g, 0.126 mol) and potassium cyanide (13.68 g, 0.210 mol) were added to a mixed solution (100 mL) of a 15% aqueous solution of (E)-4-(2,4-dimethylphenyl)-3-butene-2-one (18.32 g, 0.105 mol) and N,N-dimethylformamide, and the mixture was heated under reflux for 6 hours. Water was added to the reac...
10.6084/m9.figshare.5104873.v1
null
Ketone
Ketone.Nitrile
null
null
c1ccccc1
null
O
null
null
CC(=O)/C=C/c1ccc(C)cc1C.[C-]#N>O>CC(=O)CC(C#N)c1ccc(C)cc1C
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-4cc3645b2fc3406b990ff55a9ee5e30d
BrBr.Nc1ccc(Cl)nn1>>Nc1nnc(Cl)cc1Br
C([O-])(O)=O.[Na+].BrBr.NC=1N=NC(=CC1)Cl>>BrC1=C(N=NC(=C1)Cl)N
Br[Br:9].[NH2:1][c:2]1[n:3][n:4][c:5]([Cl:6])[cH:7][cH:8]1>>[NH2:1][c:2]1[n:3][n:4][c:5]([Cl:6])[cH:7][c:8]1[Br:9]
BrBr.Nc1ccc(Cl)nn1
Nc1nnc(Cl)cc1Br
null
null
CO
Functional Group Interconversion
Bromination
3b22a5d23572bfe9ad1502a182eb9a0357f308a16eb4f4f5e1618044bed6ab38
3c4065ab4a8681675e06a527dcad54d701c7bfdcac9f73f87773b05034108934
c1ccnnc1
Br-[Br;H0;D1;+0:1].[Cl;D1;H0:2]-[c:3]1:[#7;a:4]:[#7;a:5]:[c:6](-[N;D1;H2:7]):[cH;D2;+0:8]:[c:9]:1>>[Br;H0;D1;+0:1]-[c;H0;D3;+0:8]1:[c:9]:[c:3](-[Cl;D1;H0:2]):[#7;a:4]:[#7;a:5]:[c:6]:1-[N;D1;H2:7]
53
[{"value": 53.0, "product": "BrC1=C(N=NC(=C1)Cl)N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 52.9, "product": "BrC1=C(N=NC(=C1)Cl)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
15
HOUR
Sodium bicarbonate (13.0 g, 155 mmol) and bromine (4.0 mL, 78 mmol) were added to a solution of 3-amino-6-chloropyridazine (10.0 g, 78 mmol) in methanol (150 mL) at room temperature, and the mixture was stirred for 15 hours. The reaction mixture was filtered, and the solvent was evaporated. Water was added thereto, whi...
10.6084/m9.figshare.5104873.v1
null
null
Aromatic halide
c1ccnnc1
c1ccnnc1
c1ccnnc1
HBr
CO
null
15
BrBr.Nc1ccc(Cl)nn1>CO>Nc1nnc(Cl)cc1Br
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-18ffd5812c2a41f39e974886d5d3b71a
CCO.Cc1ccccc1.Nc1nnc(Cl)cc1Br>>Cc1ccc(-c2cc(Cl)nnc2N)c(C)c1
C(C)O.C([O-])([O-])=O.[Na+].[Na+].NC=1N=NC(=CC1Br)Cl.C1(=CC=CC=C1)C.O>>ClC1=CC(=C(N=N1)N)C1=C(C=C(C=C1)C)C
OC[CH3:15].[CH3:1][c:2]1[cH:3][cH:4][cH:5][cH:14][cH:16]1.Br[c:6]1[cH:7][c:8]([Cl:9])[n:10][n:11][c:12]1[NH2:13]>>[CH3:1][c:2]1[cH:3][cH:4][c:5](-[c:6]2[cH:7][c:8]([Cl:9])[n:10][n:11][c:12]2[NH2:13])[c:14]([CH3:15])[cH:16]1
CCO.Cc1ccccc1.Nc1nnc(Cl)cc1Br
Cc1ccc(-c2cc(Cl)nnc2N)c(C)c1
null
null
null
C-C Coupling
OtherReaction
378e6cf61b1154372bf750950dd7ae6cbdcca521fb592851187e74793d6227b8
af1238a0d333620701e826be7a9367863896c568351b293f0287634647ec2581
c1ccc(-c2ccnnc2)cc1
Br-[c;H0;D3;+0:1]1:[c:2]:[c:3](-[Cl;D1;H0:4]):[#7;a:5]:[#7;a:6]:[c:7]:1-[N;D1;H2:8].O-C-[CH3;D1;+0:9].[c:10]1:[c:11]:[c:12]:[c:13]:[cH;D2;+0:14]:[cH;D2;+0:15]:1>>[CH3;D1;+0:9]-[c;H0;D3;+0:15]1:[c:10]:[c:11]:[c:12]:[c:13]:[c;H0;D3;+0:14]:1-[c;H0;D3;+0:1]1:[c:2]:[c:3](-[Cl;D1;H0:4]):[#7;a:5]:[#7;a:6]:[c:7]:1-[N;D1;H2:8]
82
[{"value": 82.0, "product": "ClC1=CC(=C(N=N1)N)C1=C(C=C(C=C1)C)C", "details": "PERCENTYIELD", "is_desired": false}]
100
CELSIUS
null
null
Ethanol (8 mL), a 2M aqueous sodium carbonate solution (4 mL), 2,4-dimethylbenzeneboric acid (650 mg, 4.3 mmol) and tetrakistriphenylphosphine palladium complex (456 mg, 0.39 mmol) were added to a solution of 3-amino-4-bromo-6-chloropyridazine (822 mg, 3.9 mmol) in toluene (40 mL), and the mixture was heated at 100° C....
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary alcohol
null
c1ccccc1.c1ccnnc1
c1ccccc1.c1ccnnc1
c1ccccc1.c1ccnnc1
HBr
null
100
null
CCO.Cc1ccccc1.Nc1nnc(Cl)cc1Br>>Cc1ccc(-c2cc(Cl)nnc2N)c(C)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-c2efd3e9c6be4ff4b11581754d31d024
Cc1ccc(-c2cc(Cl)nnc2N)c(C)c1>>Cc1ccc(-c2ccnnc2N)c(C)c1
C(=O)[O-].[NH4+].ClC1=CC(=C(N=N1)N)C1=C(C=C(C=C1)C)C>>CC1=C(C=CC(=C1)C)C1=C(N=NC=C1)N
Cl[c:8]1[cH:7][c:6](-[c:5]2[cH:4][cH:3][c:2]([CH3:1])[cH:15][c:13]2[CH3:14])[c:11]([NH2:12])[n:10][n:9]1>>[CH3:1][c:2]1[cH:3][cH:4][c:5](-[c:6]2[cH:7][cH:8][n:9][n:10][c:11]2[NH2:12])[c:13]([CH3:14])[cH:15]1
Cc1ccc(-c2cc(Cl)nnc2N)c(C)c1
Cc1ccc(-c2ccnnc2N)c(C)c1
null
[Pd]
CO
Functional Group Interconversion
Aromatic dehalogenation
11fec97dc22aabf340de6dd16bd9ed47791a1ff823f957f6e3aa8baf8018c49f
56de34d4a44cb25d9380269ee5e138b0f24b40a3a0db22c5508049dc775a861f
c1ccc(-c2ccnnc2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[#7;a:3]:[c:4]:[c:5]:[c:6]:1>>[#7;a:3]1:[#7;a:2]:[cH;D2;+0:1]:[c:6]:[c:5]:[c:4]:1
100.4
[{"value": 99.0, "product": "CC1=C(C=CC(=C1)C)C1=C(N=NC=C1)N", "details": "PERCENTYIELD", "is_desired": false}, {"value": 100.4, "product": "CC1=C(C=CC(=C1)C)C1=C(N=NC=C1)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
10% Pd—C (759 mg, 50 wt %) and ammonium formate (1.23 g, 19 mmol) were added to a solution of 6-chloro-4-(2,4-dimethylphenyl)-3-pyridazineamine (759 mg, 3.2 mmol) in methanol (40 mL), and the mixture was heated under reflux for 1 hour. The reaction solution was filtered through Celite, and the solvent was evaporated. T...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
null
c1ccnnc1
c1ccnnc1
c1ccccc1.c1ccnnc1
Other
[Pd].CO
null
null
Cc1ccc(-c2cc(Cl)nnc2N)c(C)c1>[Pd].CO>Cc1ccc(-c2ccnnc2N)c(C)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-caf162bcebbc4f10bff043f94df86b92
CCC(=O)C(Cl)C(=O)OC.Cc1ccc(-c2ccnnc2N)c(C)c1>>CCc1nc2c(-c3ccc(C)cc3C)ccnn2c1C(=O)OC
ClC(C(=O)OC)C(CC)=O.CC1=C(C=CC(=C1)C)C1=C(N=NC=C1)N>>COC(=O)C1=C(N=C2N1N=CC=C2C2=C(C=C(C=C2)C)C)CC
O=[C:3]([CH2:2][CH3:1])[CH:19](Cl)[C:20](=[O:21])[O:22][CH3:23].[NH2:4][c:5]1[c:6](-[c:7]2[cH:8][cH:9][c:10]([CH3:11])[cH:12][c:13]2[CH3:14])[cH:15][cH:16][n:17][n:18]1>>[CH3:1][CH2:2][c:3]1[n:4][c:5]2[c:6](-[c:7]3[cH:8][cH:9][c:10]([CH3:11])[cH:12][c:13]3[CH3:14])[cH:15][cH:16][n:17][n:18]2[c:19]1[C:20](=[O:21])[O:22]...
CCC(=O)C(Cl)C(=O)OC.Cc1ccc(-c2ccnnc2N)c(C)c1
CCc1nc2c(-c3ccc(C)cc3C)ccnn2c1C(=O)OC
null
null
O
Aromatic Heterocycle Formation
OtherReaction
e9a3a6063b8692570315ac7f7821b744f54b8f587cd5476dacd07314c341cb27
31aa25659cf5accd41f8ff85a49e4d2b829110bf1926ff7161f2261cc71e0db2
c1ccc(-c2ccnn3ccnc23)cc1
Cl-[CH;D3;+0:1](-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5])-[C;H0;D3;+0:6](=O)-[C:7]-[C;D1;H3:8].[NH2;D1;+0:9]-[c:10](:[c:11]):[n;H0;D2;+0:12]:[#7;a:13]:[c:14]>>[C;D1;H3:8]-[C:7]-[c;H0;D3;+0:6]1:[n;H0;D2;+0:9]:[c:10](:[c:11]):[n;H0;D3;+0:12](:[#7;a:13]:[c:14]):[c;H0;D3;+0:1]:1-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5]
37
[{"value": 37.0, "product": "COC(=O)C1=C(N=C2N1N=CC=C2C2=C(C=C(C=C2)C)C)CC", "details": "PERCENTYIELD", "is_desired": false}]
155
CELSIUS
null
null
Methyl 2-chloro-3-oxopentanoate (5 mL) was added to 4-(2,4-dimethylphenyl)-3-pyridazineamine (640 mg, 3.2 mmol), and the mixture was heated at 155° C. for 30 minutes. Water was added to the resulting reaction mixture, and the mixture was extracted with ethyl acetate. The organic layer was washed with a 5N aqueous sodiu...
10.6084/m9.figshare.5104873.v1
null
Secondary halide.Ketone.Ester.Primary amine
Ester
c1ccnnc1
c1cnn2ccnc2c1
c1ccccc1.c1cnn2ccnc2c1
HCl
O
155
null
CCC(=O)C(Cl)C(=O)OC.Cc1ccc(-c2ccnnc2N)c(C)c1>O>CCc1nc2c(-c3ccc(C)cc3C)ccnn2c1C(=O)OC
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-ddb96ed4486247d3b9e4c63487fdc840
CCOC(=O)CBr.CSC(=Nc1ncc(C)cc1Br)SC>>CCOC(=O)c1c(SC)nc2c(Br)cc(C)cn12
BrCC(=O)OCC.BrC=1C(=NC=C(C1)C)N=C(SC)SC.C(C)N(CC)CC>>C(C)OC(=O)C1=C(N=C2N1C=C(C=C2Br)C)SC
Br[CH2:6][C:4]([O:3][CH2:2][CH3:1])=[O:5].CS[C:7]([S:8][CH3:9])=[N:10][c:11]1[c:12]([Br:13])[cH:14][c:15]([CH3:16])[cH:17][n:18]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[c:7]([S:8][CH3:9])[n:10][c:11]2[c:12]([Br:13])[cH:14][c:15]([CH3:16])[cH:17][n:18]12
CCOC(=O)CBr.CSC(=Nc1ncc(C)cc1Br)SC
CCOC(=O)c1c(SC)nc2c(Br)cc(C)cn12
null
null
O
Aromatic Heterocycle Formation
OtherReaction
ea4a591bb663a1a0c0d4cef4431d53eb59d599cc9e7e27e70212973e585b65fb
f7e1f7b75eaaa242da7c0fbcc1aa8ff0732ddd85decf84eb68979986ec93c0bd
c1ccn2ccnc2c1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C:5].C-S-[C;H0;D3;+0:6](-[#16:7]-[C;D1;H3:8])=[N;H0;D2;+0:9]-[c:10](:[c:11]):[n;H0;D2;+0:12]:[c:13]:[c:14]>>[C:5]-[#8:4]-[C:2](=[O;D1;H0:3])-[c;H0;D3;+0:1]1:[c;H0;D3;+0:6](-[#16:7]-[C;D1;H3:8]):[n;H0;D2;+0:9]:[c:10](:[c:11]):[n;H0;D3;+0:12]:1:[c:13]:[c:14]
null
[]
60
CELSIUS
4
HOUR
Ethyl bromoacetate (5.4 g) was added to methyl N-(3-bromo-5-methyl-2-pyridyl)(methylsulfanyl)methaneimidothioate, and the mixture was stirred at 60° C. for 4 hours. After cooled to room temperature, triethylamine was added to treat the material, and water was further added thereto. The reaction mixture was extracted wi...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Monosulfide.Monosulfide
Ester.Monosulfide
c1ccncc1
c1ccn2ccnc2c1
c1ccn2ccnc2c1
HBr
O
60
4
CCOC(=O)CBr.CSC(=Nc1ncc(C)cc1Br)SC>O>CCOC(=O)c1c(SC)nc2c(Br)cc(C)cn12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-61a7d60a91a74ecf9ad599979327e9da
CCOC(=O)c1c(SC)nc2c(Br)cc(C)cn12>>CSc1nc2c(Br)cc(C)cn2c1C(=O)O
C(C)OC(=O)C1=C(N=C2N1C=C(C=C2Br)C)SC.[OH-].[Na+].Cl>>BrC=1C=2N(C=C(C1)C)C(=C(N2)SC)C(=O)O
CC[O:16][C:14]([c:13]1[c:3]([S:2][CH3:1])[n:4][c:5]2[c:6]([Br:7])[cH:8][c:9]([CH3:10])[cH:11][n:12]21)=[O:15]>>[CH3:1][S:2][c:3]1[n:4][c:5]2[c:6]([Br:7])[cH:8][c:9]([CH3:10])[cH:11][n:12]2[c:13]1[C:14](=[O:15])[OH:16]
CCOC(=O)c1c(SC)nc2c(Br)cc(C)cn12
CSc1nc2c(Br)cc(C)cn2c1C(=O)O
null
null
C(C)O
Deprotection
Ester saponification (alkyl deprotection)
d872e08ad5c85a4add6cd04e6e987e73fead5f79b3f30ba61a81ba5029b29894
38ae1ee78433b9acfb0390501446149c80f88f23ac2d84c60b3369bdab75cec9
c1ccn2ccnc2c1
C-C-[O;H0;D2;+0:1]-[C:2](=[O;D1;H0:3])-[c:4](:[#7;a:5]):[c:6]:[#7;a:7]>>[#7;a:5]:[c:4](-[C:2](=[O;D1;H0:3])-[OH;D1;+0:1]):[c:6]:[#7;a:7]
90.4
[{"value": 90.4, "product": "BrC=1C=2N(C=C(C1)C)C(=C(N2)SC)C(=O)O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
8-Bromo-6-methyl-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-carboxylic acid ethyl ester (1.33 g) was dissolved in ethanol (50 mL), then a 5N aqueous sodium hydroxide solution (3 mL) was added thereto, and the mixture was stirred under reflux for 1 hour. Ice was added to the reaction mixture, then 2N hydrochloric acid (8...
10.6084/m9.figshare.5104873.v1
null
Ester
Carboxylic acid
null
null
c1ccn2ccnc2c1
Other
C(C)O
null
null
CCOC(=O)c1c(SC)nc2c(Br)cc(C)cn12>C(C)O>CSc1nc2c(Br)cc(C)cn2c1C(=O)O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-e26e30ffe1064f57b436a8732bb972fc
CCCI.CSc1nc2c(Br)cc(C)cn2c1NC(=O)OC(C)(C)C>>CCCN(C(=O)OC(C)(C)C)c1c(SC)nc2c(Br)cc(C)cn12
O.[H-].[Na+].BrC=1C=2N(C=C(C1)C)C(=C(N2)SC)NC(OC(C)(C)C)=O.ICCC>>BrC=1C=2N(C=C(C1)C)C(=C(N2)SC)N(C(OC(C)(C)C)=O)CCC
I[CH2:3][CH2:2][CH3:1].[NH:4]([C:5](=[O:6])[O:7][C:8]([CH3:9])([CH3:10])[CH3:11])[c:12]1[c:13]([S:14][CH3:15])[n:16][c:17]2[c:18]([Br:19])[cH:20][c:21]([CH3:22])[cH:23][n:24]12>>[CH3:1][CH2:2][CH2:3][N:4]([C:5](=[O:6])[O:7][C:8]([CH3:9])([CH3:10])[CH3:11])[c:12]1[c:13]([S:14][CH3:15])[n:16][c:17]2[c:18]([Br:19])[cH:20]...
CCCI.CSc1nc2c(Br)cc(C)cn2c1NC(=O)OC(C)(C)C
CCCN(C(=O)OC(C)(C)C)c1c(SC)nc2c(Br)cc(C)cn12
null
null
CN(C=O)C
Heteroatom Alkylation and Arylation
N-alkylation of secondary amines with alkyl halides
5da873da5e065666521679df8db5a1d2754540edd93ae40997847c9a24dedeb3
c05cd517c346aa4e8e8e58218c491edaea33d354b5dba9eb90dac8ad97104f73
c1ccn2ccnc2c1
I-[CH2;D2;+0:1]-[C:2]-[C;D1;H3:3].[#16:4]-[c:5]1:[#7;a:6]:[c:7]:[#7;a:8](:[c:9]):[c:10]:1-[NH;D2;+0:11]-[C:12](=[O;D1;H0:13])-[#8:14]-[C:15](-[C;D1;H3:16])(-[C;D1;H3:17])-[C;D1;H3:18]>>[#16:4]-[c:5]1:[#7;a:6]:[c:7]:[#7;a:8](:[c:9]):[c:10]:1-[N;H0;D3;+0:11](-[CH2;D2;+0:1]-[C:2]-[C;D1;H3:3])-[C:12](=[O;D1;H0:13])-[#8:14]...
97.1
[{"value": 97.1, "product": "BrC=1C=2N(C=C(C1)C)C(=C(N2)SC)N(C(OC(C)(C)C)=O)CCC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
10
MINUTE
tert-Butyl N-[8-bromo-6-methyl-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-yl]carbamate (123 mg) was dissolved in N,N-dimethylformamide (10 mL), then sodium hydride (65% in oil; 15 mg) was added thereto under ice-cooling, and the mixture was stirred for 10 minutes. Iodopropane (67 mg) was added thereto under ice-cooling,...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Carbamic ester
Carbamic ester
null
null
c1ccn2ccnc2c1
HI
CN(C=O)C
null
0.166667
CCCI.CSc1nc2c(Br)cc(C)cn2c1NC(=O)OC(C)(C)C>CN(C=O)C>CCCN(C(=O)OC(C)(C)C)c1c(SC)nc2c(Br)cc(C)cn12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-7aa3a44957624ee9a9e210aa85916a72
CCCN(C(=O)OC(C)(C)C)c1c(SC)nc2c(Br)cc(C)cn12>>CCCNc1c(SC)nc2c(Br)cc(C)cn12
BrC=1C=2N(C=C(C1)C)C(=C(N2)SC)N(C(OC(C)(C)C)=O)CCC.Cl.C(C)(=O)OCC.[OH-].[Na+]>>BrC=1C=2N(C=C(C1)C)C(=C(N2)SC)NCCC
CC(C)(C)OC(=O)[N:4]([CH2:3][CH2:2][CH3:1])[c:5]1[c:6]([S:7][CH3:8])[n:9][c:10]2[c:11]([Br:12])[cH:13][c:14]([CH3:15])[cH:16][n:17]12>>[CH3:1][CH2:2][CH2:3][NH:4][c:5]1[c:6]([S:7][CH3:8])[n:9][c:10]2[c:11]([Br:12])[cH:13][c:14]([CH3:15])[cH:16][n:17]12
CCCN(C(=O)OC(C)(C)C)c1c(SC)nc2c(Br)cc(C)cn12
CCCNc1c(SC)nc2c(Br)cc(C)cn12
null
null
C(C)(=O)OCC
Reduction
Boc amine deprotection
bbda4640db5f48af4538caded12fdadd56eacd6d4e5f7aefe46282d665df167e
a94b29c7264c852156fc1cdd4a0951a4fc26c06d0edc9e50c743825dbf79e3fd
c1ccn2ccnc2c1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1](-[C:2]-[C:3])-[c:4]1:[#7;a:5](:[c:6]):[c:7]:[#7;a:8]:[c:9]:1-[#16:10]>>[#16:10]-[c:9]1:[#7;a:8]:[c:7]:[#7;a:5](:[c:6]):[c:4]:1-[NH;D2;+0:1]-[C:2]-[C:3]
null
[]
null
null
20
HOUR
tert-Butyl N-[8-bromo-6-methyl-2-(methysulfanyl)imidazo[1,2-a]pyridin-3-yl]-N-propylcarbamate was dissolved in ethyl acetate (5 mL), then a 4N hydrochloric acid-ethyl acetate solution (10 mL) was added thereto at room temperature, and the mixture was stirred at room temperature for 20 hours. Under ice-cooling, a 5N aqu...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
null
null
c1ccn2ccnc2c1
HO-
C(C)(=O)OCC
null
20
CCCN(C(=O)OC(C)(C)C)c1c(SC)nc2c(Br)cc(C)cn12>C(C)(=O)OCC>CCCNc1c(SC)nc2c(Br)cc(C)cn12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-714abe1a9d0f4f08a934c9727575f9bf
CCC=O.CCCNc1c(SC)nc2c(Br)cc(C)cn12>>CCCN(CCC)c1c(SC)nc2c(Br)cc(C)cn12
[BH4-].[Na+].BrC=1C=2N(C=C(C1)C)C(=C(N2)SC)NCCC.C(CC)=O.[OH-].[Na+].S(O)(O)(=O)=O>>BrC=1C=2N(C=C(C1)C)C(=C(N2)SC)N(CCC)CCC
O=[CH:5][CH2:6][CH3:7].[CH3:1][CH2:2][CH2:3][NH:4][c:8]1[c:9]([S:10][CH3:11])[n:12][c:13]2[c:14]([Br:15])[cH:16][c:17]([CH3:18])[cH:19][n:20]12>>[CH3:1][CH2:2][CH2:3][N:4]([CH2:5][CH2:6][CH3:7])[c:8]1[c:9]([S:10][CH3:11])[n:12][c:13]2[c:14]([Br:15])[cH:16][c:17]([CH3:18])[cH:19][n:20]12
CCC=O.CCCNc1c(SC)nc2c(Br)cc(C)cn12
CCCN(CCC)c1c(SC)nc2c(Br)cc(C)cn12
null
null
O1CCCC1.O
Heteroatom Alkylation and Arylation
OtherReaction
6d9c60e7c47e75322fc9565d992b855788f3516a27cb14d7f9ed299e190b30d3
2d03f38884b1fbb0c0d6e6f2de31afb25102fec87f347c3a123e064c1bfef0ad
c1ccn2ccnc2c1
O=[CH;D2;+0:1]-[C:2]-[C;D1;H3:3].[#16:4]-[c:5]1:[#7;a:6]:[c:7]:[#7;a:8](:[c:9]):[c:10]:1-[NH;D2;+0:11]-[C:12]-[C:13]>>[#16:4]-[c:5]1:[#7;a:6]:[c:7]:[#7;a:8](:[c:9]):[c:10]:1-[N;H0;D3;+0:11](-[C:12]-[C:13])-[CH2;D2;+0:1]-[C:2]-[C;D1;H3:3]
67.6
[{"value": 67.6, "product": "BrC=1C=2N(C=C(C1)C)C(=C(N2)SC)N(CCC)CCC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
3
HOUR
N-[8-Bromo-6-methyl-2-(methylsulfanyl)imidazo[1,2-a]pyridin-3-yl]-N-propylamine (103 mg) and propionaldehyde (57 mg) were dissolved in tetrahydrofuran (1.2 mL), then 3M sulfuric acid (0.24 mL) was added thereto, follwed by adding sodium borohydride (24 mg) under ice-cooling, and then the mixture was stirred for 3 hours...
10.6084/m9.figshare.5104873.v1
null
Aldehyde.Secondary amine
Tertiary amine
null
null
c1ccn2ccnc2c1
Other
O1CCCC1.O
null
3
CCC=O.CCCNc1c(SC)nc2c(Br)cc(C)cn12>O1CCCC1.O>CCCN(CCC)c1c(SC)nc2c(Br)cc(C)cn12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-53f8dfa59be24e519705658fa14c16ab
CCOC(=O)CBr.COc1nccnc1N=C(SC)SC>>CCOC(=O)c1c(SC)nc2c(OC)nccn12
O.BrCC(=O)OCC.COC=1C(=NC=CN1)N=C(SC)SC>>COC=1C=2N(C=CN1)C(=C(N2)SC)C(=O)OCC
Br[CH2:6][C:4]([O:3][CH2:2][CH3:1])=[O:5].CS[C:7]([S:8][CH3:9])=[N:10][c:11]1[c:12]([O:13][CH3:14])[n:15][cH:16][cH:17][n:18]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[c:7]([S:8][CH3:9])[n:10][c:11]2[c:12]([O:13][CH3:14])[n:15][cH:16][cH:17][n:18]12
CCOC(=O)CBr.COc1nccnc1N=C(SC)SC
CCOC(=O)c1c(SC)nc2c(OC)nccn12
null
null
C(C)#N
Aromatic Heterocycle Formation
OtherReaction
3c267dccfae8261a70f72143b4e4810b305c259e0418e4dd3527c59c22d14363
f7e1f7b75eaaa242da7c0fbcc1aa8ff0732ddd85decf84eb68979986ec93c0bd
c1cn2ccnc2cn1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C:5].C-S-[C;H0;D3;+0:6](-[#16:7]-[C;D1;H3:8])=[N;H0;D2;+0:9]-[c:10]1:[n;H0;D2;+0:11]:[c:12]:[c:13]:[#7;a:14]:[c:15]:1-[#8:16]>>[#8:16]-[c:15]1:[#7;a:14]:[c:13]:[c:12]:[n;H0;D3;+0:11]2:[c:10]:1:[n;H0;D2;+0:9]:[c;H0;D3;+0:6](-[#16:7]-[C;D1;H3:8]):[c;H0;D3;+0:1]:2-[C:2](=[O;D1;...
null
[]
100
CELSIUS
14
HOUR
Ethyl bromoacetate (18.5 mL) and iso-dipropylethylamine (29 mL) were added to a solution of methyl N-(3-methoxy-2-pyrazinyl)-(methylsulfanyl)methaneimidothioate (19.1 g) in acetonitrile (42 mL), and the mixture was heated under stirring at 100° C. for 14 hours. After the reaction mixture was cooled to room temperature,...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Monosulfide.Monosulfide
Ester.Monosulfide
c1cnccn1
c1cn2ccnc2cn1
c1cn2ccnc2cn1
HBr
C(C)#N
100
14
CCOC(=O)CBr.COc1nccnc1N=C(SC)SC>C(C)#N>CCOC(=O)c1c(SC)nc2c(OC)nccn12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-7abdf09d550e4ee88ce0c2159dad6a0b
COc1ccc(B(O)O)c(C)c1.Nc1nnc(Cl)cc1Br>>COc1ccc(-c2cc(Cl)nnc2N)c(C)c1
BrC1=C(N=NC(=C1)Cl)N.COC1=CC(=C(C=C1)B(O)O)C.C([O-])([O-])=O.[Na+].[Na+]>>ClC1=CC(=C(N=N1)N)C1=C(C=C(C=C1)OC)C
OB(O)[c:6]1[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:17][c:15]1[CH3:16].Br[c:7]1[cH:8][c:9]([Cl:10])[n:11][n:12][c:13]1[NH2:14]>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6](-[c:7]2[cH:8][c:9]([Cl:10])[n:11][n:12][c:13]2[NH2:14])[c:15]([CH3:16])[cH:17]1
COc1ccc(B(O)O)c(C)c1.Nc1nnc(Cl)cc1Br
COc1ccc(-c2cc(Cl)nnc2N)c(C)c1
null
null
C1(=CC=CC=C1)C.C(C)O
C-C Coupling
Suzuki coupling with boronic acids
adacd3669bc1a24c4361e5305292c80a681bc380fae785e3ebcb5b72415c1784
08d2969413ef1a2cd5b43667268ba178160c7b55545bf48018e31f2b019632ec
c1ccc(-c2ccnnc2)cc1
Br-[c;H0;D3;+0:1]1:[c:2]:[c:3](-[Cl;D1;H0:4]):[#7;a:5]:[#7;a:6]:[c:7]:1-[N;D1;H2:8].O-B(-O)-[c;H0;D3;+0:9](:[c:10]:[c:11]):[c:12](-[C;D1;H3:13]):[c:14]>>[C;D1;H3:13]-[c:12](:[c:14]):[c;H0;D3;+0:9](-[c;H0;D3;+0:1]1:[c:2]:[c:3](-[Cl;D1;H0:4]):[#7;a:5]:[#7;a:6]:[c:7]:1-[N;D1;H2:8]):[c:10]:[c:11]
54.9
[{"value": 54.9, "product": "ClC1=CC(=C(N=N1)N)C1=C(C=C(C=C1)OC)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
12
HOUR
4-Bromo-6-chloro-3-pyridazineamine (12 g) and 4-methoxy-2-methylphenylboronic acid (10.5 g) were dissolved in a mixed solvent of toluene (240 mL) and ethanol (45 mL), then tetrakistriphenylphosphine palladium complex (6.7 g) and a 2M aqueous sodium carbonate solution (24 mL) were added thereto, and the mixture was heat...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Boronic acid
null
c1ccccc1.c1ccnnc1
c1ccccc1.c1ccnnc1
c1ccccc1.c1ccnnc1
HBr.B
C1(=CC=CC=C1)C.C(C)O
100
12
COc1ccc(B(O)O)c(C)c1.Nc1nnc(Cl)cc1Br>C1(=CC=CC=C1)C.C(C)O>COc1ccc(-c2cc(Cl)nnc2N)c(C)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-07a7055c4d7c49e6ac9330386c5fda72
COc1ccc(-c2cc(Cl)nnc2N)c(C)c1>>COc1ccc(-c2ccnnc2N)c(C)c1
C(=O)[O-].[NH4+].ClC1=CC(=C(N=N1)N)C1=C(C=C(C=C1)OC)C>>COC1=CC(=C(C=C1)C1=C(N=NC=C1)N)C
Cl[c:9]1[cH:8][c:7](-[c:6]2[cH:5][cH:4][c:3]([O:2][CH3:1])[cH:16][c:14]2[CH3:15])[c:12]([NH2:13])[n:11][n:10]1>>[CH3:1][O:2][c:3]1[cH:4][cH:5][c:6](-[c:7]2[cH:8][cH:9][n:10][n:11][c:12]2[NH2:13])[c:14]([CH3:15])[cH:16]1
COc1ccc(-c2cc(Cl)nnc2N)c(C)c1
COc1ccc(-c2ccnnc2N)c(C)c1
null
[Pd]
CO
Functional Group Interconversion
Aromatic dehalogenation
11fec97dc22aabf340de6dd16bd9ed47791a1ff823f957f6e3aa8baf8018c49f
56de34d4a44cb25d9380269ee5e138b0f24b40a3a0db22c5508049dc775a861f
c1ccc(-c2ccnnc2)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[#7;a:3]:[c:4]:[c:5]:[c:6]:1>>[#7;a:2]1:[#7;a:3]:[c:4]:[c:5]:[c:6]:[cH;D2;+0:1]:1
90.6
[{"value": 90.6, "product": "COC1=CC(=C(C=C1)C1=C(N=NC=C1)N)C", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
10% Pd—C (hydrous product; 7.89 g) and ammonium formate (11.96 g) were added to a solution of 6-chloro-4-(4-methoxy-2-methylphenyl)-3-pyridazineamine (7.89 g) in methanol (100 mL), and the mixture was heated under reflux for 1.5 hours. The reaction mixture was filtered through Celite, and the solvent was evaporated. Th...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
null
c1ccnnc1
c1ccnnc1
c1ccccc1.c1ccnnc1
Other
[Pd].CO
null
null
COc1ccc(-c2cc(Cl)nnc2N)c(C)c1>[Pd].CO>COc1ccc(-c2ccnnc2N)c(C)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d011a34f340141d78c8d6e01cd5e9f78
CCOC(=O)CBr.COc1ccc(-c2ccnnc2N=C(SC)SC)c(C)c1>>CCOC(=O)c1c(SC)nc2c(-c3ccc(OC)cc3C)ccnn12
O.BrCC(=O)OCC.C(C)N(C(C)C)C(C)C.COC1=CC(=C(C=C1)C1=C(N=NC=C1)N=C(SC)SC)C>>COC1=CC(=C(C=C1)C=1C=2N(N=CC1)C(=C(N2)SC)C(=O)OCC)C
Br[CH2:6][C:4]([O:3][CH2:2][CH3:1])=[O:5].CS[C:7]([S:8][CH3:9])=[N:10][c:11]1[c:12](-[c:13]2[cH:14][cH:15][c:16]([O:17][CH3:18])[cH:19][c:20]2[CH3:21])[cH:22][cH:23][n:24][n:25]1>>[CH3:1][CH2:2][O:3][C:4](=[O:5])[c:6]1[c:7]([S:8][CH3:9])[n:10][c:11]2[c:12](-[c:13]3[cH:14][cH:15][c:16]([O:17][CH3:18])[cH:19][c:20]3[CH3:...
CCOC(=O)CBr.COc1ccc(-c2ccnnc2N=C(SC)SC)c(C)c1
CCOC(=O)c1c(SC)nc2c(-c3ccc(OC)cc3C)ccnn12
null
null
C(C)#N
Aromatic Heterocycle Formation
OtherReaction
bc7c29467fce76f06e95a31f2573538d88769b2abbf0dae6a32a1db90239edc4
f7e1f7b75eaaa242da7c0fbcc1aa8ff0732ddd85decf84eb68979986ec93c0bd
c1ccc(-c2ccnn3ccnc23)cc1
Br-[CH2;D2;+0:1]-[C:2](=[O;D1;H0:3])-[#8:4]-[C:5].C-S-[C;H0;D3;+0:6](-[#16:7]-[C;D1;H3:8])=[N;H0;D2;+0:9]-[c:10](:[c:11]):[n;H0;D2;+0:12]:[#7;a:13]:[c:14]>>[C:5]-[#8:4]-[C:2](=[O;D1;H0:3])-[c;H0;D3;+0:1]1:[c;H0;D3;+0:6](-[#16:7]-[C;D1;H3:8]):[n;H0;D2;+0:9]:[c:10](:[c:11]):[n;H0;D3;+0:12]:1:[#7;a:13]:[c:14]
null
[]
100
CELSIUS
14
HOUR
Ethyl bromoacetate (0.87 mL) and i-Pr2EtN (1.36 mL) were added to a solution of methyl N-[4-(4-methoxy-2-methylphenyl)-3-pyridazinyl]-(methylsulfanyl)methaneimidothioate (1.25 g) in acetonitrile (10 mL), and the mixture was heated under stirring at 100° C. for 14 hours. The reaction mixture was cooled to room temperatu...
10.6084/m9.figshare.5104873.v1
null
Primary halide.Ester.Monosulfide.Monosulfide
Ester.Monosulfide
c1ccnnc1
c1cnn2ccnc2c1
c1ccccc1.c1cnn2ccnc2c1
HBr
C(C)#N
100
14
CCOC(=O)CBr.COc1ccc(-c2ccnnc2N=C(SC)SC)c(C)c1>C(C)#N>CCOC(=O)c1c(SC)nc2c(-c3ccc(OC)cc3C)ccnn12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-b3ef0ed44cec4ad4b299aee980ab90e1
CCC(N)CO.Clc1cc(Cl)ncn1>>CCC(CO)Nc1cc(Cl)ncn1
ClC1=NC=NC(=C1)Cl.NC(CO)CC>>ClC1=CC(=NC=N1)NC(CO)CC
[CH3:1][CH2:2][CH:3]([CH2:4][OH:5])[NH2:6].Cl[c:7]1[cH:8][c:9]([Cl:10])[n:11][cH:12][n:13]1>>[CH3:1][CH2:2][CH:3]([CH2:4][OH:5])[NH:6][c:7]1[cH:8][c:9]([Cl:10])[n:11][cH:12][n:13]1
CCC(N)CO.Clc1cc(Cl)ncn1
CCC(CO)Nc1cc(Cl)ncn1
null
null
O1CCOCC1
Heteroatom Alkylation and Arylation
N-arylation (Buchwald-Hartwig/Ullmann-Goldberg)
c38b7155556ff28144ae37859ff6668b20d59da60c705d26b158542b6d8385da
71a04ae650defc5edd86a92f43c304e981a05f07ff76248da8d4155f3905a29d
c1cncnc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](-[Cl;D1;H0:6]):[c:7]:1.[C:8]-[C:9](-[C:10])-[NH2;D1;+0:11]>>[C:8]-[C:9](-[C:10])-[NH;D2;+0:11]-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](-[Cl;D1;H0:6]):[c:7]:1
null
[]
null
null
null
null
4,6-Dichloropyrimidine (5.0 g) and 2-amino-1-butanol (6.5 mL) were heated under reflux in 1,4-dioxane (26 mL) for 1 hour. The reaction mixture was evaporated, and the resulting residue was purified by silica gel column chromatography (ethyl acetate:n-hexane=1:10) to give the title compound (5.6 g) as a pale orange oil....
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary amine
Secondary amine
c1cncnc1
c1cncnc1
c1cncnc1
HCl
O1CCOCC1
null
null
CCC(N)CO.Clc1cc(Cl)ncn1>O1CCOCC1>CCC(CO)Nc1cc(Cl)ncn1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-7aeaa9b5e887432ea2aa67e82af68d84
CCC(CO)Nc1cc(Cl)ncn1>>CCC(CO)Nc1ccncn1
ClC1=CC(=NC=N1)NC(CO)CC.[OH-].[Na+]>>N1=CN=C(C=C1)NC(CO)CC
Cl[c:9]1[cH:8][c:7]([NH:6][CH:3]([CH2:2][CH3:1])[CH2:4][OH:5])[n:12][cH:11][n:10]1>>[CH3:1][CH2:2][CH:3]([CH2:4][OH:5])[NH:6][c:7]1[cH:8][cH:9][n:10][cH:11][n:12]1
CCC(CO)Nc1cc(Cl)ncn1
CCC(CO)Nc1ccncn1
null
[Pd].[Pd]
C(C)O
Functional Group Interconversion
Aromatic dehalogenation
76895d15d2d466b89a30aacc2ef4edbb246f8c7b092db05f2443e4acbf4f85b3
56de34d4a44cb25d9380269ee5e138b0f24b40a3a0db22c5508049dc775a861f
c1cncnc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[#7;a:4]:[c:5](-[#7:6]):[c:7]:1>>[#7:6]-[c:5]1:[#7;a:4]:[c:3]:[#7;a:2]:[cH;D2;+0:1]:[c:7]:1
null
[]
null
null
null
null
2-[(6-Chloro-4-pyrimidinyl)amino]-1-butanol was dissolved in ethanol (110 mL), which was sequentially added with a 5N aqueous sodium hydroxide solution (5.5 mL) and Pd—C (hydrous product; 0.55 g), and hydrogenation was performed under hydrogen atmosphere at a normal temperature and a normal pressure. After completion o...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide
null
c1cncnc1
c1cncnc1
c1cncnc1
Other
[Pd].[Pd].C(C)O
null
null
CCC(CO)Nc1cc(Cl)ncn1>[Pd].[Pd].C(C)O>CCC(CO)Nc1ccncn1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-5ce564191dcc48cfa674d17d783155ab
CCC(CO)Nc1ncncc1Br>>CCC1CN2C=NC=C(Br)C2=N1
BrC=1C(=NC=NC1)NC(CO)CC.S(=O)(Cl)Cl>>BrC=1C=2N(C=NC1)CC(N2)CC
O[CH2:4][CH:3]([CH2:2][CH3:1])[NH:12][c:11]1[n:5][cH:6][n:7][cH:8][c:9]1[Br:10]>>[CH3:1][CH2:2][CH:3]1[CH2:4][N:5]2[CH:6]=[N:7][CH:8]=[C:9]([Br:10])[C:11]2=[N:12]1
CCC(CO)Nc1ncncc1Br
CCC1CN2C=NC=C(Br)C2=N1
null
null
C=1(C(=CC=CC1)C)C
Reduction
OtherReaction
6a2ef22bb6c74569235803d2ce7a2fea50e3f12dac8dc022e2ff3ebc53e59331
9374feb200a4832853bbfb58e352f944bf17983311287662fa53041448433835
C1=CC2=NCCN2C=N1
O-[CH2;D2;+0:1]-[C:2](-[C:3])-[NH;D2;+0:4]-[c;H0;D3;+0:5]1:[n;H0;D2;+0:6]:[cH;D2;+0:7]:[n;H0;D2;+0:8]:[cH;D2;+0:9]:[c;H0;D3;+0:10]:1-[Br;D1;H0:11]>>[Br;D1;H0:11]-[C;H0;D3;+0:10]1=[CH;D2;+0:9]-[N;H0;D2;+0:8]=[CH;D2;+0:7]-[N;H0;D3;+0:6]2-[CH2;D2;+0:1]-[C:2](-[C:3])-[N;H0;D2;+0:4]=[C;H0;D3;+0:5]-1-2
98.1
[{"value": 98.1, "product": "BrC=1C=2N(C=NC1)CC(N2)CC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
100
CELSIUS
1
DAY
2-[(5-Bromo-4-pyrimidinyl)amino]-1-butanol (3.3 g) was dissolved in xylene (27 mL), then thionyl chloride (4.9 mL) was added thereto, and the mixture was heated under stirring at 100° C. for 1 day. The precipitated crystals were collected by filtration and suspended in a 1M aqueous sodium carbonate solution. This mixtu...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Primary alcohol.Secondary amine
Alkenyl halide.Tertiary amine
c1cncnc1
C1=CC2=NCCN2C=N1
C1=CC2=NCCN2C=N1
HO-
C=1(C(=CC=CC1)C)C
100
24
CCC(CO)Nc1ncncc1Br>C=1(C(=CC=CC1)C)C>CCC1CN2C=NC=C(Br)C2=N1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-f6be0fdcc7454cd9853af08eab5f7538
CCC1CN2C=NC=C(Br)C2=N1>>CCc1cn2cncc(Br)c2n1
BrC=1C=2N(C=NC1)CC(N2)CC>>BrC=1C=2N(C=NC1)C=C(N2)CC
[CH3:1][CH2:2][CH:3]1[CH2:4][N:5]2[CH:6]=[N:7][CH:8]=[C:9]([Br:10])[C:11]2=[N:12]1>>[CH3:1][CH2:2][c:3]1[cH:4][n:5]2[cH:6][n:7][cH:8][c:9]([Br:10])[c:11]2[n:12]1
CCC1CN2C=NC=C(Br)C2=N1
CCc1cn2cncc(Br)c2n1
null
[O-2].[O-2].[Mn+4]
C1(=CC=CC=C1)C
Aromatic Heterocycle Formation
OtherReaction
31d8cb45bfee75d7dc58ada016878d2887065c520615c9f014f8358557a8518a
ec223f8fb0661e09955f4db94fe3afc2006ddb41271eb6ffedd6e26bd39cc60d
c1cc2nccn2cn1
[Br;D1;H0:1]-[C;H0;D3;+0:2]1=[CH;D2;+0:3]-[N;H0;D2;+0:4]=[CH;D2;+0:5]-[N;H0;D3;+0:6]2-[CH2;D2;+0:7]-[CH;D3;+0:8](-[C:9]-[C;D1;H3:10])-[N;H0;D2;+0:11]=[C;H0;D3;+0:12]-1-2>>[Br;D1;H0:1]-[c;H0;D3;+0:2]1:[cH;D2;+0:3]:[n;H0;D2;+0:4]:[cH;D2;+0:5]:[n;H0;D3;+0:6]2:[cH;D2;+0:7]:[c;H0;D3;+0:8](-[C:9]-[C;D1;H3:10]):[n;H0;D2;+0:11...
43.7
[{"value": 43.7, "product": "BrC=1C=2N(C=NC1)C=C(N2)CC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
90
CELSIUS
1
DAY
8-Bromo-2-ethyl-2,3-dihydroimidazo[1,2-c]pyrimidine (3.0 g) was dissolved in toluene (60 mL), then activated manganese(IV) dioxide (3.5 g) was added thereto, and the mixture was heated under stirring at 90° C. for 1 day. Manganese(IV) oxide was filtered off through Celite, and the solvent was evaporated. The resulting ...
10.6084/m9.figshare.5104873.v1
null
Alkenyl halide.Tertiary amine
Aromatic halide
C1=CC2=NCCN2C=N1
c1cc2nccn2cn1
c1cc2nccn2cn1
null
[O-2].[O-2].[Mn+4].C1(=CC=CC=C1)C
90
24
CCC1CN2C=NC=C(Br)C2=N1>[O-2].[O-2].[Mn+4].C1(=CC=CC=C1)C>CCc1cn2cncc(Br)c2n1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3cca3e00bbc64b42a99f319374361cd1
CCc1cn2cncc(Br)c2n1.CN(C)C=O>>CCc1nc2c(Br)cncn2c1C=O
BrC=1C=2N(C=NC1)C=C(N2)CC.P(=O)(Cl)(Cl)Cl.CN(C=O)C>>BrC=1C=2N(C=NC1)C(=C(N2)CC)C=O
[CH3:1][CH2:2][c:3]1[n:4][c:5]2[c:6]([Br:7])[cH:8][n:9][cH:10][n:11]2[cH:12]1.CN(C)[CH:13]=[O:14]>>[CH3:1][CH2:2][c:3]1[n:4][c:5]2[c:6]([Br:7])[cH:8][n:9][cH:10][n:11]2[c:12]1[CH:13]=[O:14]
CCc1cn2cncc(Br)c2n1.CN(C)C=O
CCc1nc2c(Br)cncn2c1C=O
null
null
null
C-C Coupling
OtherReaction
8a035d1da1b950c730fa68e247c5a4ba7fa43b3d0c30089a09a34056dd417eea
f0bd75a0630092c31f21f61f4a015c77ae0dff14a0b742b4370d7a38fda490f7
c1cc2nccn2cn1
C-N(-C)-[CH;D2;+0:1]=[O;D1;H0:2].[C:3]-[c:4]1:[#7;a:5]:[c:6]2:[c:7]:[c:8]:[#7;a:9]:[c:10]:[#7;a:11]:2:[cH;D2;+0:12]:1>>[C:3]-[c:4]1:[#7;a:5]:[c:6]2:[c:7]:[c:8]:[#7;a:9]:[c:10]:[#7;a:11]:2:[c;H0;D3;+0:12]:1-[CH;D2;+0:1]=[O;D1;H0:2]
null
[]
null
null
1
DAY
8-Bromo-2-ethylimidazo[1,2-c]pyrimidine (1.0 g) was added to a mixture of phosphorus oxychloride (1.2 mL) and N,N-dimethylformamide (4.4 mL) at room temperature. The mixture was heated under stirring as it was at 80° C. for 1 day. After cooled to room temperature, it was poured slowly on ice. The material was extracted...
10.6084/m9.figshare.5104873.v1
null
Tertiary amide
Aldehyde
c1cc2nccn2cn1
c1cc2nccn2cn1
c1cc2nccn2cn1
Other
null
null
24
CCc1cn2cncc(Br)c2n1.CN(C)C=O>>CCc1nc2c(Br)cncn2c1C=O
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-cf2dfacaa1cf4bf29ee8cbdd73c6f90d
CC(C)(C)O.CCc1nc2c(-c3ccc(Cl)cc3Cl)nccn2c1C(=O)O.[N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1>>CCc1nc2c(-c3ccc(Cl)cc3Cl)nccn2c1NC(=O)OC(C)(C)C
ClC1=C(C=CC(=C1)Cl)C=1C=2N(C=CN1)C(=C(N2)CC)C(=O)O.C(C)(C)(C)O.C1(=CC=CC=C1)P(=O)(C1=CC=CC=C1)N=[N+]=[N-].C(C)N(CC)CC>>ClC1=C(C=CC(=C1)Cl)C=1C=2N(C=CN1)C(=C(N2)CC)NC(OC(C)(C)C)=O
[OH:23][C:24]([CH3:25])([CH3:26])[CH3:27].O[C:21]([c:19]1[c:3]([CH2:2][CH3:1])[n:4][c:5]2[c:6](-[c:7]3[cH:8][cH:9][c:10]([Cl:11])[cH:12][c:13]3[Cl:14])[n:15][cH:16][cH:17][n:18]21)=[O:22].[N-]=[N+]=[N:20]P(=O)(c1ccccc1)c1ccccc1>>[CH3:1][CH2:2][c:3]1[n:4][c:5]2[c:6](-[c:7]3[cH:8][cH:9][c:10]([Cl:11])[cH:12][c:13]3[Cl:14...
CC(C)(C)O.CCc1nc2c(-c3ccc(Cl)cc3Cl)nccn2c1C(=O)O.[N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1
CCc1nc2c(-c3ccc(Cl)cc3Cl)nccn2c1NC(=O)OC(C)(C)C
null
null
null
Protection
OtherReaction
ff75c28e1d3e252861948e87159e36873498ae0641a66598d10c7093178e37d2
b944663b5278c281edc6c72611c69e4309c3f5728dcd63d51413085e18c1d2e7
c1ccc(-c2nccn3ccnc23)cc1
O-[C;H0;D3;+0:1](=[O;D1;H0:2])-[c;H0;D3;+0:3]1:[#7;a:4]2:[c:5]:[c:6]:[#7;a:7]:[c:8]:[c:9]:2:[#7;a:10]:[c:11]:1-[C: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:12]-[c:11]1:[#7;a:10]:[c:9]2:[c:8]:[#7;a:7]:[c:6]:[c:5]:[#7;a:4]:2:[c;...
null
[]
null
null
2
HOUR
The resulting 8-(2,4-dichlorophenyl)-2-ethylimidazo[1,2-a]pyrazine-3-carboxylic acid was dissolved in tert-butyl alcohol (15 mL), then diphenylphosphorylazide (0.69 mL, 3.2 mmol) and triethylamine (0.49 mL, 3.5 mmol) were added thereto, and the mixture was stirred for 2 hours by heating under reflux. After being cooled...
10.6084/m9.figshare.5104873.v1
null
Carboxylic acid.Azide.Tertiary alcohol
Carbamic ester.Ether.Boc
c1cn2ccnc2cn1.c1ccccc1.c1ccccc1
c1cn2ccnc2cn1
c1ccccc1.c1cn2ccnc2cn1
HO-
null
null
2
CC(C)(C)O.CCc1nc2c(-c3ccc(Cl)cc3Cl)nccn2c1C(=O)O.[N-]=[N+]=NP(=O)(c1ccccc1)c1ccccc1>>CCc1nc2c(-c3ccc(Cl)cc3Cl)nccn2c1NC(=O)OC(C)(C)C
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-47b92d2b3d10436eb9c94b440aa7bc1c
CCCN(C(=O)OC(C)(C)C)c1c(CC)nc2c(-c3ccc(Cl)cc3Cl)nccn12>>CCCNc1c(CC)nc2c(-c3ccc(Cl)cc3Cl)nccn12
ClC1=C(C=CC(=C1)Cl)C=1C=2N(C=CN1)C(=C(N2)CC)N(C(OC(C)(C)C)=O)CCC.Cl.C(C)(=O)OCC.[OH-].[Na+]>>ClC1=C(C=CC(=C1)Cl)C=1C=2N(C=CN1)C(=C(N2)CC)NCCC
CC(C)(C)OC(=O)[N:4]([CH2:3][CH2:2][CH3:1])[c:5]1[c:6]([CH2:7][CH3:8])[n:9][c:10]2[c:11](-[c:12]3[cH:13][cH:14][c:15]([Cl:16])[cH:17][c:18]3[Cl:19])[n:20][cH:21][cH:22][n:23]12>>[CH3:1][CH2:2][CH2:3][NH:4][c:5]1[c:6]([CH2:7][CH3:8])[n:9][c:10]2[c:11](-[c:12]3[cH:13][cH:14][c:15]([Cl:16])[cH:17][c:18]3[Cl:19])[n:20][cH:2...
CCCN(C(=O)OC(C)(C)C)c1c(CC)nc2c(-c3ccc(Cl)cc3Cl)nccn12
CCCNc1c(CC)nc2c(-c3ccc(Cl)cc3Cl)nccn12
null
null
C(C)(=O)OCC
Reduction
Boc amine deprotection
bbda4640db5f48af4538caded12fdadd56eacd6d4e5f7aefe46282d665df167e
a94b29c7264c852156fc1cdd4a0951a4fc26c06d0edc9e50c743825dbf79e3fd
c1ccc(-c2nccn3ccnc23)cc1
C-C(-C)(-C)-O-C(=O)-[N;H0;D3;+0:1](-[C:2]-[C:3])-[c:4]1:[#7;a:5]2:[c:6]:[c:7]:[#7;a:8]:[c:9]:[c:10]:2:[#7;a:11]:[c:12]:1-[C:13]>>[C:3]-[C:2]-[NH;D2;+0:1]-[c:4]1:[#7;a:5]2:[c:6]:[c:7]:[#7;a:8]:[c:9]:[c:10]:2:[#7;a:11]:[c:12]:1-[C:13]
null
[]
null
null
20
HOUR
tert-Butyl N-[8-(2,4-dichlorophenyl)-2-ethylimidazo[1,2-a]pyrazin-3-yl]-N-propylcarbamate was dissolved in ethyl acetate (1 mL), then a 4N hydrochloric acid-ethyl acetate solution (1.9 mL, 7.4 mmol) was added thereto at room temperature, and the mixture was stirred at room temperature for 20 hours. Under ice-cooling, a...
10.6084/m9.figshare.5104873.v1
null
Carbamic ester.Ether.Boc
Secondary amine
null
null
c1ccccc1.c1cn2ccnc2cn1
HO-
C(C)(=O)OCC
null
20
CCCN(C(=O)OC(C)(C)C)c1c(CC)nc2c(-c3ccc(Cl)cc3Cl)nccn12>C(C)(=O)OCC>CCCNc1c(CC)nc2c(-c3ccc(Cl)cc3Cl)nccn12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-c3dedaa32842468091f1cd400f894547
CCC(=O)C(Cl)C(=O)OC.Nc1ncc(Cl)nc1-c1ccc(Cl)cc1Cl>>CCc1nc2c(-c3ccc(Cl)cc3Cl)nc(Cl)cn2c1C(=O)OC
ClC=1N=C(C(=NC1)N)C1=C(C=C(C=C1)Cl)Cl.ClC(C(=O)OC)C(CC)=O>>COC(=O)C1=C(N=C2N1C=C(N=C2C2=C(C=C(C=C2)Cl)Cl)Cl)CC
O=[C:3]([CH2:2][CH3:1])[CH:20](Cl)[C:21](=[O:22])[O:23][CH3:24].[NH2:4][c:5]1[c:6](-[c:7]2[cH:8][cH:9][c:10]([Cl:11])[cH:12][c:13]2[Cl:14])[n:15][c:16]([Cl:17])[cH:18][n:19]1>>[CH3:1][CH2:2][c:3]1[n:4][c:5]2[c:6](-[c:7]3[cH:8][cH:9][c:10]([Cl:11])[cH:12][c:13]3[Cl:14])[n:15][c:16]([Cl:17])[cH:18][n:19]2[c:20]1[C:21](=[...
CCC(=O)C(Cl)C(=O)OC.Nc1ncc(Cl)nc1-c1ccc(Cl)cc1Cl
CCc1nc2c(-c3ccc(Cl)cc3Cl)nc(Cl)cn2c1C(=O)OC
null
null
null
Aromatic Heterocycle Formation
OtherReaction
9ef3f8c7d8012f16862df6e6d5d64f5e5c28836502935c9f0f51594189d35521
31aa25659cf5accd41f8ff85a49e4d2b829110bf1926ff7161f2261cc71e0db2
c1ccc(-c2nccn3ccnc23)cc1
Cl-[CH;D3;+0:1](-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5])-[C;H0;D3;+0:6](=O)-[C:7]-[C;D1;H3:8].[Cl;D1;H0:9]-[c:10]1:[#7;a:11]:[c:12](-[c:13]):[c:14](-[NH2;D1;+0:15]):[n;H0;D2;+0:16]:[c:17]:1>>[C;D1;H3:8]-[C:7]-[c;H0;D3;+0:6]1:[n;H0;D2;+0:15]:[c:14]2:[c:12](-[c:13]):[#7;a:11]:[c:10](-[Cl;D1;H0:9]):[c:17]:[n;H0;D3;+0:16]:...
null
[]
170
CELSIUS
null
null
5-Chloro-3-(2,4-dichlorophenyl)-2-pyrazineamine (1.1 g, 4.0 mmol) and methyl 2-chloro-3-oxopentanoate (5.7 mL) were mixed, and the mixture was heated under stirring at 170° C. 3 hours. After being allowed to cool, the reaction mixture was purified by silica gel column chromatography (n-hexane:ethyl acetate=20:1), and t...
10.6084/m9.figshare.5104873.v1
null
Secondary halide.Ketone.Ester.Primary amine
Ester
c1cnccn1
c1cn2ccnc2cn1
c1ccccc1.c1cn2ccnc2cn1
HCl
null
170
null
CCC(=O)C(Cl)C(=O)OC.Nc1ncc(Cl)nc1-c1ccc(Cl)cc1Cl>>CCc1nc2c(-c3ccc(Cl)cc3Cl)nc(Cl)cn2c1C(=O)OC
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-d354e8b3a5f94cb7ac254cd7b9f2205f
CCc1nc2c(Br)nc(C)cn2c1C(=O)OC.OB(O)c1ccc(Cl)cc1Cl>>CCc1nc2c(-c3ccc(Cl)cc3Cl)nc(C)cn2c1C(=O)OC
COC(=O)C1=C(N=C2N1C=C(N=C2Br)C)CC.ClC1=C(C=CC(=C1)Cl)B(O)O>>COC(=O)C1=C(N=C2N1C=C(N=C2C2=C(C=C(C=C2)Cl)Cl)C)CC
Br[c:6]1[c:5]2[n:4][c:3]([CH2:2][CH3:1])[c:20]([C:21](=[O:22])[O:23][CH3:24])[n:19]2[cH:18][c:16]([CH3:17])[n:15]1.OB(O)[c:7]1[cH:8][cH:9][c:10]([Cl:11])[cH:12][c:13]1[Cl:14]>>[CH3:1][CH2:2][c:3]1[n:4][c:5]2[c:6](-[c:7]3[cH:8][cH:9][c:10]([Cl:11])[cH:12][c:13]3[Cl:14])[n:15][c:16]([CH3:17])[cH:18][n:19]2[c:20]1[C:21](=...
CCc1nc2c(Br)nc(C)cn2c1C(=O)OC.OB(O)c1ccc(Cl)cc1Cl
CCc1nc2c(-c3ccc(Cl)cc3Cl)nc(C)cn2c1C(=O)OC
null
null
C1(=CC=CC=C1)C.CO
C-C Coupling
Suzuki coupling with boronic acids
f5f68366c974e5c94b4bc855fbfd92fc71b74cb90c46aa9127be16df4ce6917f
08d2969413ef1a2cd5b43667268ba178160c7b55545bf48018e31f2b019632ec
c1ccc(-c2nccn3ccnc23)cc1
Br-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[c:4]:[#7;a:5]2:[c:6](-[C:7](-[#8:8])=[O;D1;H0:9]):[c:10]:[#7;a:11]:[c:12]:2:1.O-B(-O)-[c;H0;D3;+0:13](:[c:14]:[c:15]):[c:16](-[Cl;D1;H0:17]):[c:18]>>[#8:8]-[C:7](=[O;D1;H0:9])-[c:6]1:[c:10]:[#7;a:11]:[c:12]2:[#7;a:5]:1:[c:4]:[c:3]:[#7;a:2]:[c;H0;D3;+0:1]:2-[c;H0;D3;+0:13](:[c:14]:[c:1...
107.4
[{"value": 107.4, "product": "COC(=O)C1=C(N=C2N1C=C(N=C2C2=C(C=C(C=C2)Cl)Cl)C)CC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
8-Bromo-2-ethyl-6-methylimidazo[1,2-a]pyrazine-3-carboxylic acid methyl ester (0.30 g, 1.0 mmol) was dissolved in a mixed solvent of toluene (5.6 mL) and methanol (1.4 mL). Then 2,4-dichlorobenzeneboronic acid (0.382 g, 2.0 mmol) and tetrakistriphenylphosphine palladium complex (116 mg, 0.1 mmol) were added thereto, an...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Boronic acid
null
c1cn2ccnc2cn1.c1ccccc1
c1ccccc1.c1cn2ccnc2cn1
c1ccccc1.c1cn2ccnc2cn1
HBr.B
C1(=CC=CC=C1)C.CO
null
null
CCc1nc2c(Br)nc(C)cn2c1C(=O)OC.OB(O)c1ccc(Cl)cc1Cl>C1(=CC=CC=C1)C.CO>CCc1nc2c(-c3ccc(Cl)cc3Cl)nc(C)cn2c1C(=O)OC
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3cf04266c89d43188ea72fd741f61495
Cc1cn2ccnc(-c3ccc(Cl)cc3Cl)c2n1.O=[N+]=O>>Cc1nc2c(-c3ccc(Cl)cc3Cl)nccn2c1[N+](=O)[O-]
ClC1=C(C=CC(=C1)Cl)C=1C=2N(C=CN1)C=C(N2)C.F[B-](F)(F)F.O=[N+]=O.O>>ClC1=C(C=CC(=C1)Cl)C=1C=2N(C=CN1)C(=C(N2)C)[N+](=O)[O-]
[CH3:1][c:2]1[n:3][c:4]2[c:5](-[c:6]3[cH:7][cH:8][c:9]([Cl:10])[cH:11][c:12]3[Cl:13])[n:14][cH:15][cH:16][n:17]2[cH:18]1.[N+:19](=[O:20])=[O:21]>>[CH3:1][c:2]1[n:3][c:4]2[c:5](-[c:6]3[cH:7][cH:8][c:9]([Cl:10])[cH:11][c:12]3[Cl:13])[n:14][cH:15][cH:16][n:17]2[c:18]1[N+:19](=[O:20])[O-:21]
Cc1cn2ccnc(-c3ccc(Cl)cc3Cl)c2n1.O=[N+]=O
Cc1nc2c(-c3ccc(Cl)cc3Cl)nccn2c1[N+](=O)[O-]
null
null
C(C)#N
Functional Group Addition
OtherReaction
57eebfeb389d6a773d16b3708a163218e309f50f4d5b0ce8352432d25e433fec
5c75a9bf759be9717d985245c85c84dbfff904ea5287869736b84fdaa57f1e27
c1ccc(-c2nccn3ccnc23)cc1
[C;D1;H3:1]-[c:2]1:[#7;a:3]:[c:4]2:[c:5]:[#7;a:6]:[c:7]:[c:8]:[#7;a:9]:2:[cH;D2;+0:10]:1.[O;D1;H0:11]=[N+;H0;D2:12]=[O;H0;D1;+0:13]>>[C;D1;H3:1]-[c:2]1:[#7;a:3]:[c:4]2:[c:5]:[#7;a:6]:[c:7]:[c:8]:[#7;a:9]:2:[c;H0;D3;+0:10]:1-[N+;H0;D3:12](-[O-;H0;D1:13])=[O;D1;H0:11]
1,323.8
[{"value": 1323.8, "product": "ClC1=C(C=CC(=C1)Cl)C=1C=2N(C=CN1)C(=C(N2)C)[N+](=O)[O-]", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
8-(2,4-Dichlorophenyl)-2-methylimidazo[1,2-a]pyrazine (0.10 g, 0.36 mmol) was dissolved in acetonitrile (0.36 mL), then nitronium tetrafluoroborate (72 mg, 0.54 mmol) was added thereto, and the mixture was stirred at room temperature for 1 hour under nitrogen atmosphere. Water was added to the reaction mixture, and it ...
10.6084/m9.figshare.5104873.v1
null
Nitroso.Nitroso
Nitro group
c1cn2ccnc2cn1
c1cn2ccnc2cn1
c1ccccc1.c1cn2ccnc2cn1
null
C(C)#N
null
1
Cc1cn2ccnc(-c3ccc(Cl)cc3Cl)c2n1.O=[N+]=O>C(C)#N>Cc1nc2c(-c3ccc(Cl)cc3Cl)nccn2c1[N+](=O)[O-]
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-1e461046a28c4037887e2fccf29aeadc
Cc1nc2c(-c3ccc(Cl)cc3Cl)nccn2c1[N+](=O)[O-]>>Cc1nc2c(-c3ccc(Cl)cc3Cl)nccn2c1N
ClC1=C(C=CC(=C1)Cl)C=1C=2N(C=CN1)C(=C(N2)C)[N+](=O)[O-].C(C)(=O)O>>ClC1=C(C=CC(=C1)Cl)C=1C=2N(C=CN1)C(=C(N2)C)N
O=[N+:19]([O-])[c:18]1[c:2]([CH3:1])[n:3][c:4]2[c:5](-[c:6]3[cH:7][cH:8][c:9]([Cl:10])[cH:11][c:12]3[Cl:13])[n:14][cH:15][cH:16][n:17]21>>[CH3:1][c:2]1[n:3][c:4]2[c:5](-[c:6]3[cH:7][cH:8][c:9]([Cl:10])[cH:11][c:12]3[Cl:13])[n:14][cH:15][cH:16][n:17]2[c:18]1[NH2:19]
Cc1nc2c(-c3ccc(Cl)cc3Cl)nccn2c1[N+](=O)[O-]
Cc1nc2c(-c3ccc(Cl)cc3Cl)nccn2c1N
null
[Fe]
C(C)O
Reduction
Reduction of nitro groups to amines
bbc242b150a51e69d3ad1caaa391f4422710431b398dcb880555f476706790be
7b0317532ea57a4fcedc1efc3e3c22eb5238d1c8330da53d4f9801fc2391f567
c1ccc(-c2nccn3ccnc23)cc1
O=[N+;H0;D3:1](-[O-])-[c:2]1:[#7;a:3]2:[c:4]:[c:5]:[#7;a:6]:[c:7]:[c:8]:2:[#7;a:9]:[c:10]:1-[C;D1;H3:11]>>[C;D1;H3:11]-[c:10]1:[#7;a:9]:[c:8]2:[c:7]:[#7;a:6]:[c:5]:[c:4]:[#7;a:3]:2:[c:2]:1-[NH2;D1;+0:1]
35.4
[{"value": 35.4, "product": "ClC1=C(C=CC(=C1)Cl)C=1C=2N(C=CN1)C(=C(N2)C)N", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
8-(2,4-Dichlorophenyl)-2-methyl-3-nitroimidazo[1,2-a]pyrazine (25 mg, 0.077 mmol) was dissolved in ethanol (0.36 mL), then acetic acid (0.5 mL) and iron powders (22 mg) were added thereto, and the mixture was stirred for 1 hour by heating under reflux. After the reaction mixture was allowed to cool, the solvent was eva...
10.6084/m9.figshare.5104873.v1
null
Nitro group
Primary amine
null
null
c1ccccc1.c1cn2ccnc2cn1
Other
[Fe].C(C)O
null
1
Cc1nc2c(-c3ccc(Cl)cc3Cl)nccn2c1[N+](=O)[O-]>[Fe].C(C)O>Cc1nc2c(-c3ccc(Cl)cc3Cl)nccn2c1N
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-8d298d32255543de800e4507a8f82d71
CCCC(=O)c1c(CC)nc2c(Cl)nccn12.COc1cc(C)cc(C)c1B(O)O>>CCCC(=O)c1c(CC)nc2c(-c3c(C)cc(C)cc3OC)nccn12
ClC=1C=2N(C=CN1)C(=C(N2)CC)C(CCC)=O.CC1=CC(=C(C(=C1)C)B(O)O)OC.O.O.O.O.O.O.O.O.[OH-].[Ba+2].[OH-]>>C(C)C=1N=C2N(C=CN=C2C2=C(C=C(C=C2C)C)OC)C1C(CCC)=O
Cl[c:12]1[c:11]2[n:10][c:7]([CH2:8][CH3:9])[c:6]([C:4]([CH2:3][CH2:2][CH3:1])=[O:5])[n:26]2[cH:25][cH:24][n:23]1.OB(O)[c:13]1[c:14]([CH3:15])[cH:16][c:17]([CH3:18])[cH:19][c:20]1[O:21][CH3:22]>>[CH3:1][CH2:2][CH2:3][C:4](=[O:5])[c:6]1[c:7]([CH2:8][CH3:9])[n:10][c:11]2[c:12](-[c:13]3[c:14]([CH3:15])[cH:16][c:17]([CH3:18...
CCCC(=O)c1c(CC)nc2c(Cl)nccn12.COc1cc(C)cc(C)c1B(O)O
CCCC(=O)c1c(CC)nc2c(-c3c(C)cc(C)cc3OC)nccn12
null
null
O.COCCOC
C-C Coupling
Suzuki coupling with boronic acids
f5f68366c974e5c94b4bc855fbfd92fc71b74cb90c46aa9127be16df4ce6917f
08d2969413ef1a2cd5b43667268ba178160c7b55545bf48018e31f2b019632ec
c1ccc(-c2nccn3ccnc23)cc1
Cl-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[c:4]:[#7;a:5]2:[c:6]:1:[#7;a:7]:[c:8]:[c:9]:2-[C:10]=[O;D1;H0:11].O-B(-O)-[c;H0;D3;+0:12](:[c:13](-[C;D1;H3:14]):[c:15]):[c:16](-[#8:17]):[c:18]>>[#8:17]-[c:16](:[c:18]):[c;H0;D3;+0:12](-[c;H0;D3;+0:1]1:[#7;a:2]:[c:3]:[c:4]:[#7;a:5]2:[c:6]:1:[#7;a:7]:[c:8]:[c:9]:2-[C:10]=[O;D1;H0:11])...
77.5
[{"value": 77.5, "product": "C(C)C=1N=C2N(C=CN=C2C2=C(C=C(C=C2C)C)OC)C1C(CCC)=O", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
null
null
1-(8-Chloro-2-ethylimidazo[1,2-a]pyrazin-3-yl)-1-butanone (226 mg, 0.90 mmol) and 4,6-dimethyl-2-methoxybenzeneboronic acid (198 mg, 1.1 mmol) were dissolved in a mixed solvent of 1,2-dimethoxyethane (4.5 mL) and water (0.75 mL). Barium hydroxide octahydrate (347 mg, 1.1 mmol) and tetrakis(triphenylphosphine)palladium ...
10.6084/m9.figshare.5104873.v1
null
Aromatic halide.Boronic acid
null
c1cn2ccnc2cn1.c1ccccc1
c1ccccc1.c1cn2ccnc2cn1
c1ccccc1.c1cn2ccnc2cn1
HCl.B
O.COCCOC
null
null
CCCC(=O)c1c(CC)nc2c(Cl)nccn12.COc1cc(C)cc(C)c1B(O)O>O.COCCOC>CCCC(=O)c1c(CC)nc2c(-c3c(C)cc(C)cc3OC)nccn12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-192e1a40a6384d7292b3d4f44ff27a9d
CCCC(=O)c1c(CC)nc2c(-c3c(C)cc(C)cc3OC)nccn12.CC[CH2][Mg][Br]>>CCCC(O)(CCC)c1c(CC)nc2c(-c3c(C)cc(C)cc3OC)nccn12
C(C)C=1N=C2N(C=CN=C2C2=C(C=C(C=C2C)C)OC)C1C(CCC)=O.C(CC)[Mg]Br.[Cl-].[NH4+]>>C(C)C=1N=C2N(C=CN=C2C2=C(C=C(C=C2C)C)OC)C1C(CCC)(CCC)O
[C:4](=[O:5])([CH2:6][CH2:7][CH3:8])[c:9]1[c:10]([CH2:11][CH3:12])[n:13][c:14]2[c:15](-[c:16]3[c:17]([CH3:18])[cH:19][c:20]([CH3:21])[cH:22][c:23]3[O:24][CH3:25])[n:26][cH:27][cH:28][n:29]12.[Br][Mg][CH2:3][CH2:2][CH3:1]>>[CH3:1][CH2:2][CH2:3][C:4]([OH:5])([CH2:6][CH2:7][CH3:8])[c:9]1[c:10]([CH2:11][CH3:12])[n:13][c:14...
CCCC(=O)c1c(CC)nc2c(-c3c(C)cc(C)cc3OC)nccn12.CC[CH2][Mg][Br]
CCCC(O)(CCC)c1c(CC)nc2c(-c3c(C)cc(C)cc3OC)nccn12
null
null
O1CCCC1
C-C Coupling
Grignard from ketone to alcohol
4737491c367e985251b8e6236de937de0f5f777bcb09b5971359565d81ed217a
5854166cd4ea706bc07d74dc79eb8f4a990bc6c5eacbf0ca947d88ee86e78fdf
c1ccc(-c2nccn3ccnc23)cc1
[Br]-[Mg]-[CH2;D2;+0:1]-[C:2]-[C;D1;H3:3].[C:4]-[c:5]1:[#7;a:6]:[c:7]2:[c:8]:[#7;a:9]:[c:10]:[c:11]:[#7;a:12]:2:[c:13]:1-[C;H0;D3;+0:14](=[O;H0;D1;+0:15])-[C:16]-[C:17]>>[C:4]-[c:5]1:[#7;a:6]:[c:7]2:[c:8]:[#7;a:9]:[c:10]:[c:11]:[#7;a:12]:2:[c:13]:1-[C;H0;D4;+0:14](-[OH;D1;+0:15])(-[C:16]-[C:17])-[CH2;D2;+0:1]-[C:2]-[C;...
null
[]
null
null
2
HOUR
The resulting 1-[2-ethyl-8-(2-methoxy-4,6-dimethylphenyl)imidazo[1,2-a]pyrazin-3-yl]-1-butanone (220 mg, 0.63 mmol) was dissolved in tetrahydrofuran (2 mL), then a 0.90M propylmagnesium bromide solution in tetrahydrofuran (3.6 mL, 3.2 mmol) was added thereto under ice-cooling, and the mixture was stirred at room temper...
10.6084/m9.figshare.5104873.v1
null
Magnesium halide.Ketone
Tertiary alcohol
null
null
c1ccccc1.c1cn2ccnc2cn1
Br-.Mg
O1CCCC1
null
2
CCCC(=O)c1c(CC)nc2c(-c3c(C)cc(C)cc3OC)nccn12.CC[CH2][Mg][Br]>O1CCCC1>CCCC(O)(CCC)c1c(CC)nc2c(-c3c(C)cc(C)cc3OC)nccn12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-193aa487bb724d47ad2b1c9bf3bf0bf9
CCCC(O)(CCC)c1c(CC)nc2c(-c3c(C)cc(C)cc3OC)nccn12>>CC/C=C(/CCC)c1c(CC)nc2c(-c3c(C)cc(C)cc3OC)nccn12
C([O-])(O)=O.[Na+].C(C)C=1N=C2N(C=CN=C2C2=C(C=C(C=C2C)C)OC)C1C(CCC)(CCC)O.C(C)N(CC)CC.CS(=O)(=O)Cl>>COC1=C(C(=CC(=C1)C)C)C=1C=2N(C=CN1)C(=C(N2)CC)\C(=C/CC)\CCC
O[C:4]([CH2:3][CH2:2][CH3:1])([CH2:5][CH2:6][CH3:7])[c:8]1[c:9]([CH2:10][CH3:11])[n:12][c:13]2[c:14](-[c:15]3[c:16]([CH3:17])[cH:18][c:19]([CH3:20])[cH:21][c:22]3[O:23][CH3:24])[n:25][cH:26][cH:27][n:28]12>>[CH3:1][CH2:2]/[CH:3]=[C:4](/[CH2:5][CH2:6][CH3:7])[c:8]1[c:9]([CH2:10][CH3:11])[n:12][c:13]2[c:14](-[c:15]3[c:16...
CCCC(O)(CCC)c1c(CC)nc2c(-c3c(C)cc(C)cc3OC)nccn12
CC/C=C(/CCC)c1c(CC)nc2c(-c3c(C)cc(C)cc3OC)nccn12
null
null
C(Cl)Cl
Functional Group Interconversion
OtherReaction
2552af78a9ee7fee2cf4bc86811ade6ce7c2595ea6de1b1217b4ecd33d9a5077
63e4ba80024292782b5f87f96975225484dff39f49e96eea21874ac0cd9091a0
c1ccc(-c2nccn3ccnc23)cc1
O-[C;H0;D4;+0:1](-[C:2]-[C:3])(-[CH2;D2;+0:4]-[C:5]-[C;D1;H3:6])-[c:7]1:[#7;a:8]2:[c:9]:[c:10]:[#7;a:11]:[c:12]:[c:13]:2:[#7;a:14]:[c:15]:1-[C:16]>>[C:16]-[c:15]1:[#7;a:14]:[c:13]2:[c:12]:[#7;a:11]:[c:10]:[c:9]:[#7;a:8]:2:[c:7]:1/[C;H0;D3;+0:1](-[C:2]-[C:3])=[CH;D2;+0:4]\[C:5]-[C;D1;H3:6]
101.4
[{"value": 101.4, "product": "COC1=C(C(=CC(=C1)C)C)C=1C=2N(C=CN1)C(=C(N2)CC)\\C(=C/CC)\\CCC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
null
null
1
HOUR
4-[2-Ethyl-8-(2-methoxy-4,6-dimethylphenyl)imidazo[1,2-a]pyrazin-3-yl]-4-heptanol (115 mg, 0.29 mmol) and triethylamine (0.48 mL, 3.5 mmol) were dissolved in methylene chloride (3 mL), then methanesulfonyl chloride (0.13 mL, 1.7 mmol) was added thereto under ice-cooling, and the mixture was stirred at room temperature ...
10.6084/m9.figshare.5104873.v1
null
Tertiary alcohol
null
null
null
c1ccccc1.c1cn2ccnc2cn1
HO-
C(Cl)Cl
null
1
CCCC(O)(CCC)c1c(CC)nc2c(-c3c(C)cc(C)cc3OC)nccn12>C(Cl)Cl>CC/C=C(/CCC)c1c(CC)nc2c(-c3c(C)cc(C)cc3OC)nccn12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-3fc9f175b03846b1aa0f510d61c8cec7
CC/C=C(/CCC)c1c(CC)nc2c(-c3c(C)cc(C)cc3OC)nccn12>>CCCC(CCC)c1c(CC)nc2c(-c3c(C)cc(C)cc3OC)nccn12
COC1=C(C(=CC(=C1)C)C)C=1C=2N(C=CN1)C(=C(N2)CC)\C(=C/CC)\CCC>>COC1=C(C(=CC(=C1)C)C)C=1C=2N(C=CN1)C(=C(N2)CC)C(CCC)CCC
[CH3:1][CH2:2]/[CH:3]=[C:4](/[CH2:5][CH2:6][CH3:7])[c:8]1[c:9]([CH2:10][CH3:11])[n:12][c:13]2[c:14](-[c:15]3[c:16]([CH3:17])[cH:18][c:19]([CH3:20])[cH:21][c:22]3[O:23][CH3:24])[n:25][cH:26][cH:27][n:28]12>>[CH3:1][CH2:2][CH2:3][CH:4]([CH2:5][CH2:6][CH3:7])[c:8]1[c:9]([CH2:10][CH3:11])[n:12][c:13]2[c:14](-[c:15]3[c:16](...
CC/C=C(/CCC)c1c(CC)nc2c(-c3c(C)cc(C)cc3OC)nccn12
CCCC(CCC)c1c(CC)nc2c(-c3c(C)cc(C)cc3OC)nccn12
null
[C].[Pd]
C(C)O
Reduction
Hydrogenation (double to single)
0bc3968b35f0839c230afb4215314da278abd4e1f10e42ec3012c5512de49ea5
312e9350dcad67590617294c0eb017edf0b9fbfe6133c06a3f393b871a889092
c1ccc(-c2nccn3ccnc23)cc1
[C:1]-[c:2]1:[#7;a:3]:[c:4]2:[c:5]:[#7;a:6]:[c:7]:[c:8]:[#7;a:9]:2:[c:10]:1/[C;H0;D3;+0:11](-[C:12]-[C:13])=[CH;D2;+0:14]\[C:15]-[C;D1;H3:16]>>[C:1]-[c:2]1:[#7;a:3]:[c:4]2:[c:5]:[#7;a:6]:[c:7]:[c:8]:[#7;a:9]:2:[c:10]:1-[CH;D3;+0:11](-[C:12]-[C:13])-[CH2;D2;+0:14]-[C:15]-[C;D1;H3:16]
54.9
[{"value": 54.9, "product": "COC1=C(C(=CC(=C1)C)C)C=1C=2N(C=CN1)C(=C(N2)CC)C(CCC)CCC", "details": "CALCULATEDPERCENTYIELD", "is_desired": false}]
45
CELSIUS
4
HOUR
2-[2-Ethyl-3-[(Z)-1-propyl-1-butenyl]imidazo[1,2-a]pyrazin-8-yl]-3,5-dimethylphenyl methyl ether (41 mg, 0.12 mmol) was dissolved in ethanol (1.5 mL), then 10% palladium-carbon (50% hydrous product; 120 mg) was added thereto, and the mixture was heated under stirring at 45° C. for 4 hours at a normal pressure under hyd...
10.6084/m9.figshare.5104873.v1
null
null
null
null
null
c1ccccc1.c1cn2ccnc2cn1
null
[C].[Pd].C(C)O
45
4
CC/C=C(/CCC)c1c(CC)nc2c(-c3c(C)cc(C)cc3OC)nccn12>[C].[Pd].C(C)O>CCCC(CCC)c1c(CC)nc2c(-c3c(C)cc(C)cc3OC)nccn12
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-0e9e6b47a37641d8819dfc59e60223ca
CC(=O)CC(C#N)c1ccc(C)cc1C.NN>>Cc1ccc(-c2cc(C)nnc2N)c(C)c1
C(C)(=O)O.O.NN.CC1=C(C=CC(=C1)C)C(CC(C)=O)C#N>>CC1=C(C=CC(=C1)C)C1=C(N=NC(=C1)C)N
O=[C:8]([CH2:7][CH:6]([c:5]1[cH:4][cH:3][c:2]([CH3:1])[cH:16][c:14]1[CH3:15])[C:12]#[N:13])[CH3:9].[NH2:10][NH2:11]>>[CH3:1][c:2]1[cH:3][cH:4][c:5](-[c:6]2[cH:7][c:8]([CH3:9])[n:10][n:11][c:12]2[NH2:13])[c:14]([CH3:15])[cH:16]1
CC(=O)CC(C#N)c1ccc(C)cc1C.NN
Cc1ccc(-c2cc(C)nnc2N)c(C)c1
null
null
C(C)O
Aromatic Heterocycle Formation
OtherReaction
6f197e66869b240851a231d1f25cb4d9d2823d9fa9f4c5d7adfd582c66000e3d
a78e9303472e036bbc8878e5b3222e30e9aba072d6de158deb64f510e46fb597
c1ccc(-c2ccnnc2)cc1
O=[C;H0;D3;+0:1](-[C;D1;H3:2])-[CH2;D2;+0:3]-[CH;D3;+0:4](-[C;H0;D2;+0:5]#[N;H0;D1;+0:6])-[c;H0;D3;+0:7](:[c:8]:[c:9]):[c:10](-[C;D1;H3:11]):[c:12].[NH2;D1;+0:13]-[NH2;D1;+0:14]>>[C;D1;H3:11]-[c:10](:[c:12]):[c;H0;D3;+0:7](-[c;H0;D3;+0:4]1:[cH;D2;+0:3]:[c;H0;D3;+0:1](-[C;D1;H3:2]):[n;H0;D2;+0:13]:[n;H0;D2;+0:14]:[c;H0;...
null
[]
null
null
null
null
Acetic acid (5 mL) and hydrazine monohydrate (2.52 g, 0.05 mol) were added to a solution of 1-(2,4-dimethylphenyl)-3-oxobutyl cyanide (10.13 g, 0.05 mol) in ethanol (100 mL), and the mixture was heated under reflux for 8 hours. The reaction mixture was evaporated as it was. Water was added thereto, and the mixture was ...
10.6084/m9.figshare.5104873.v1
null
Hydrazine.Ketone.Nitrile
Primary amine
null
c1ccnnc1
c1ccccc1.c1ccnnc1
HO-
C(C)O
null
null
CC(=O)CC(C#N)c1ccc(C)cc1C.NN>C(C)O>Cc1ccc(-c2cc(C)nnc2N)c(C)c1
ord_dataset-c3a75813d0b24864aa4f7cd526efd6aa
ord-4cf939a5affd4488b7559b3acba5ae40
CCC(=O)C(Cl)C(=O)OC.Cc1ccc(-c2cc(C)nnc2N)c(C)c1>>CCc1nc2c(-c3ccc(C)cc3C)cc(C)nn2c1C(=O)OC
ClC(C(=O)OC)C(CC)=O.CC1=C(C=CC(=C1)C)C1=C(N=NC(=C1)C)N.O>>COC(=O)C1=C(N=C2N1N=C(C=C2C2=C(C=C(C=C2)C)C)C)CC
O=[C:3]([CH2:2][CH3:1])[CH:20](Cl)[C:21](=[O:22])[O:23][CH3:24].[NH2:4][c:5]1[c:6](-[c:7]2[cH:8][cH:9][c:10]([CH3:11])[cH:12][c:13]2[CH3:14])[cH:15][c:16]([CH3:17])[n:18][n:19]1>>[CH3:1][CH2:2][c:3]1[n:4][c:5]2[c:6](-[c:7]3[cH:8][cH:9][c:10]([CH3:11])[cH:12][c:13]3[CH3:14])[cH:15][c:16]([CH3:17])[n:18][n:19]2[c:20]1[C:...
CCC(=O)C(Cl)C(=O)OC.Cc1ccc(-c2cc(C)nnc2N)c(C)c1
CCc1nc2c(-c3ccc(C)cc3C)cc(C)nn2c1C(=O)OC
null
null
CN(C=O)C
Aromatic Heterocycle Formation
OtherReaction
e9a3a6063b8692570315ac7f7821b744f54b8f587cd5476dacd07314c341cb27
31aa25659cf5accd41f8ff85a49e4d2b829110bf1926ff7161f2261cc71e0db2
c1ccc(-c2ccnn3ccnc23)cc1
Cl-[CH;D3;+0:1](-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5])-[C;H0;D3;+0:6](=O)-[C:7]-[C;D1;H3:8].[NH2;D1;+0:9]-[c:10](:[c:11]):[n;H0;D2;+0:12]:[#7;a:13]:[c:14]>>[C;D1;H3:8]-[C:7]-[c;H0;D3;+0:6]1:[n;H0;D2;+0:9]:[c:10](:[c:11]):[n;H0;D3;+0:12](:[#7;a:13]:[c:14]):[c;H0;D3;+0:1]:1-[C:2](=[O;D1;H0:3])-[#8:4]-[C;D1;H3:5]
null
[]
140
CELSIUS
null
null
Methyl 2-chloro-3-oxopentanoate (7 mL) was added to a solution of the resulting 4-(2,4-dimethylphenyl)-6-methyl-3-pyridazinamine in N,N-dimethylformamide (60 mL), and the mixture was heated at 140° C. for 6 hours. Water was added thereto, which was extracted with ethyl acetate. The organic layer was washed with an aque...
10.6084/m9.figshare.5104873.v1
null
Secondary halide.Ketone.Ester.Primary amine
Ester
c1ccnnc1
c1cnn2ccnc2c1
c1ccccc1.c1cnn2ccnc2c1
HCl
CN(C=O)C
140
null
CCC(=O)C(Cl)C(=O)OC.Cc1ccc(-c2cc(C)nnc2N)c(C)c1>CN(C=O)C>CCc1nc2c(-c3ccc(C)cc3C)cc(C)nn2c1C(=O)OC