Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:3][C:4]1[CH:9]=[CH:8][C:7]([CH2:10][C:11]2[C:12]([O:17][C@@H:18]3[O:26][C@H:25]([CH2:27][OH:28])[C@@H:23]([OH:24])[C@H:21]([OH:22])[C@H:19]3[OH:20])=[N:13][NH:14][C:15]=2[CH3:16])=[CH:6][CH:5]=1)[CH3:2].I[CH2:30][CH3:31]>>[CH2:30]([N:14]1[C:15]([CH3:16])=[C:11]([CH2:10][C:7]2[CH:8]=[CH:9][C:4]([O:3][CH2:1][CH3:2])=[CH:5][CH:6]=2)[C:12]([O:17][C@@H:18]2[O:26][C@H:25]([CH2:27][OH:28])[C@@H:23]([OH:24])[C@H:21]([OH:22])[C@H:19]2[OH:20])=[N:13]1)[CH3:31]
Reactant: CCI
Reactant: CCOc1ccc(Cc2c(O[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)n[nH]c2C)cc1
Product: CCOc1ccc(Cc2c(O[C@@H]3O[C@H](CO)[C@@H](O)[C@H](O)[C@H]3O)nn(CC)c2C)cc1

Procedure:
The title compound was prepared in a similar manner to that described in Reference Example 63 using 4-[(4-ethoxyphenyl)methyl]-3-(β-D-glucopyranosyloxy)-5-methyl-1H-pyrazole instead of 3-(β-D-glucopyranosyloxy)-4-[(4-iso-propoxyphenyl)methyl]-5-methyl-1H-pyrazole and using iodoethane instead of 1-iodopropane.
Reaction SMILES: [C:1]([O:5][C:6]([NH:8][C:9](=[N:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])SC)=[O:7])([CH3:4])([CH3:3])[CH3:2].[CH3:20][NH:21][CH3:22]>>[C:1]([O:5][C:6]([NH:8][C:9](=[N:12][C:13]([O:15][C:16]([CH3:19])([CH3:18])[CH3:17])=[O:14])[N:21]([CH3:22])[CH3:20])=[O:7])([CH3:4])([CH3:3])[CH3:2]
Reactant: CNC
Reactant: CSC(=NC(=O)OC(C)(C)C)NC(=O)OC(C)(C)C
Product: CN(C)C(=NC(=O)OC(C)(C)C)NC(=O)OC(C)(C)C
Temperature: 25 °C
Reaction time: 18 h

Procedure:
1,3-Di-(tert-butoxycarbonyl)-2-methyl-isothiourea (Japanese Patent Unexamined Publication No. 2-3661) (3.00 g) was dissolved in a 50% aqueous dimethylamine solution (40 ml) and the resulting solution was stirred at room temperature for 18 hours. The solvent was distilled off under reduced pressure and the residue was purified by a silica gel column chromatography to obtain the desired compound (2.58 g).
Reaction SMILES: [O:1]=[C:2]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[CH:3]([O:10][C:11](=[O:35])[C@H:12]1[CH2:16][C@@H:15]([O:17][Si](C(C)(C)C)(C)C)[CH2:14][N:13]1[C:25]([O:27][CH2:28][C:29]1[CH:34]=[CH:33][CH:32]=[CH:31][CH:30]=1)=[O:26])[C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.Cl.C([O-])(O)=O.[Na+]>CO.C1COCC1>[O:1]=[C:2]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)[CH:3]([O:10][C:11](=[O:35])[C@H:12]1[CH2:16][C@@H:15]([OH:17])[CH2:14][N:13]1[C:25]([O:27][CH2:28][C:29]1[CH:30]=[CH:31][CH:32]=[CH:33][CH:34]=1)=[O:26])[C:4]1[CH:5]=[CH:6][CH:7]=[CH:8][CH:9]=1
Reactant: CC(C)(C)[Si](C)(C)O[C@@H]1C[C@H](C(=O)OC(C(=O)c2ccccc2)c2ccccc2)N(C(=O)OCc2ccccc2)C1
Agent: Cl
Agent: O=C([O-])O
Agent: [Na+]
Solvent: CO
Solvent: C1CCOC1
Product: O=C(c1ccccc1)C(OC(=O)[C@H]1C[C@@H](O)CN1C(=O)OCc1ccccc1)c1ccccc1
Temperature: 25 °C
Reaction time: 24 h
Yield: 80.3 %

Procedure:
To a solution of cis-4-(tert-butyldimethylsilyloxy)-N-benzyloxycarbonyl-D-proline 2-oxo-1,2-diphenylethyl ester (21.62 g) in MeOH-THF (2:1, 380 mL) was added 1N HCl (76 mL) at 5° C., and the mixture was stirred at room temperature for 24 hours. To the reaction mixture was added NaHCO3 (6.7 g) at 5° C. The organic solvent was evaporated, and the residue was extracted with EtOAc. The organic layer was washed with water and brine, dried (MgSO4), and evaporated in vacuo. The residue was purified by silica gal column chromatography (hexane-EtOAc, 2:1˜1:3 elution) to give cis4-hydroxy-N-benzyloxycarbonyl-D-proline 2-oxo-1,2-diphenylethyl ester (13.90 g).
Reaction SMILES: [CH2:1]([S:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:10]=1[NH:18]C(=O)C(F)(F)F)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.N>CO>[CH2:1]([S:8][C:9]1[CH:14]=[CH:13][C:12]([N+:15]([O-:17])=[O:16])=[CH:11][C:10]=1[NH2:18])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: O=C(Nc1cc([N+](=O)[O-])ccc1SCc1ccccc1)C(F)(F)F
Agent: N
Solvent: CO
Product: Nc1cc([N+](=O)[O-])ccc1SCc1ccccc1
Temperature: 60 °C
Yield: 90.2 %

Procedure:
To the solution of N-(2-(benzylthio)-5-nitrophenyl)-2,2,2-trifluoroacetamide (17.5 g, 49 mmol) in methanol (100 ml), added ammonia (15 ml, 7N in CH3OH). The reaction was heated at 60° C. for 2 hours. Then concentrated, extracted with EtOAc, washed with water and brine, dried over Na2SO4. Concentrated to give 11.5 g 2-(benzylthio)-5-nitroaniline as product.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([NH:9][C:10](=[O:18])[C:11]2[CH:16]=[CH:15][C:14]([Cl:17])=[N:13][CH:12]=2)[CH:5]=[CH:6][C:7]=1[Cl:8].[F:19][C:20]1[CH:21]=[C:22]([CH:26]=[CH:27][CH:28]=1)[C:23](O)=[O:24]>>[Cl:17][C:14]1[CH:15]=[CH:16][C:11]([C:10]([NH:9][C:4]2[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([NH:1][C:23](=[O:24])[C:22]3[CH:26]=[CH:27][CH:28]=[C:20]([F:19])[CH:21]=3)[CH:3]=2)=[O:18])=[CH:12][N:13]=1
Reactant: O=C(O)c1cccc(F)c1
Reactant: Nc1cc(NC(=O)c2ccc(Cl)nc2)ccc1Cl
Product: O=C(Nc1ccc(Cl)c(NC(=O)c2cccc(F)c2)c1)c1ccc(Cl)nc1

Procedure:
N-(3-amino-4-chlorophenyl)-6-chloronicotinamide (0.16 mmol) was used in general procedure 2 with 3-fluorobenzoic acid (0.83 mmol). The product was purified by RP-HPLC to give 6-chloro-N-(4-chloro-3-(3-fluorobenzamido)phenyl)nicotinamide. MS (Q1) 404.3 (M)+
Reaction SMILES: [CH2:1]([N:4]([CH2:10][CH:11]=O)[C:5](=[O:9])[O:6][CH2:7][CH3:8])[CH:2]=[CH2:3].[NH:13]([CH2:15]C(O)=O)[CH3:14]>C1(C)C=CC=CC=1>[CH3:14][N:13]1[CH2:15][CH2:3][CH:2]2[CH:11]1[CH2:10][N:4]([C:5]([O:6][CH2:7][CH3:8])=[O:9])[CH2:1]2
Reactant: C=CCN(CC=O)C(=O)OCC
Reactant: CNCC(=O)O
Solvent: Cc1ccccc1
Product: CCOC(=O)N1CC2CCN(C)C2C1

Procedure:
8.6 g (50 mmol) of ethyl N-allyl-N-(2-oxoethyl) -carbamate are heated under reflux overnight with 4.5 g (50 mmol) of sarcosine in 200 ml of toluene. The mixture is concentrated and the residue is distilled.
Reaction SMILES: [Br:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:17]=[CH:16][C:12]([C:13]([OH:15])=O)=[C:11]([N+:18]([O-:20])=[O:19])[CH:10]=2)[C:5](=[O:21])[N:4]([CH3:22])[CH:3]=1.F[P-](F)(F)(F)(F)F.N1(O[P+](N(C)C)(N(C)C)N(C)C)C2C=CC=CC=2N=N1.C(N(C(C)C)CC)(C)C.[CH3:59][NH:60][CH2:61][CH2:62][OH:63]>CN(C=O)C>[Br:1][C:2]1[N:7]=[C:6]([NH:8][C:9]2[CH:17]=[CH:16][C:12]([C:13]([N:60]([CH2:61][CH2:62][OH:63])[CH3:59])=[O:15])=[C:11]([N+:18]([O-:20])=[O:19])[CH:10]=2)[C:5](=[O:21])[N:4]([CH3:22])[CH:3]=1
Reactant: CNCCO
Reactant: Cn1cc(Br)nc(Nc2ccc(C(=O)O)c([N+](=O)[O-])c2)c1=O
Agent: CN(C)[P+](On1nnc2ccccc21)(N(C)C)N(C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CN(C)C=O
Solvent: CCN(C(C)C)C(C)C
Product: CN(CCO)C(=O)c1ccc(Nc2nc(Br)cn(C)c2=O)cc1[N+](=O)[O-]
Reaction time: 0.25 h
Yield: 90.6 %

Procedure:
4-(6-Bromo-4-methyl-3-oxo-3,4-dihydro-pyrazin-2-ylamino)-2-nitro-benzoic acid (3) (1.0 g, 2.72 mmol), (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate [BOP] (120 mg, 2.72 mmol,), diisopropylethylamine (1.42 mL, 8.15 mmol) and 2-methylaminoethanol (0.33 mL, 4.07 mmol) are dissolved in DMF (25 mL) at room temperature and allowed to react for 60 min. The reaction is quenched by the addition of water (120 mL) and the resulting suspension was allowed to stir for 15 min. The suspension is then filtered, washed with water (3×50 mL) and then air-dried to give 4-(6-bromo-4-methyl-3-oxo-3,4-dihydro-pyrazin-2-ylamino)-N-(2-hydroxy-ethyl)-N-methyl-2-nitro-benzamide (4) as a yellow solid (1.05 g).
Reaction SMILES: FC(F)(F)C([NH:5][C:6]1[S:7][CH:8]=[C:9]([C:11](=[N:29][O:30][CH3:31])[C:12]([NH:14][CH:15]2[C:27](=[O:28])[N:17]3[C:18]([C:24]([OH:26])=[O:25])=[C:19]([CH3:23])[CH:20]([CH3:22])[S:21][C@H:16]23)=[O:13])[N:10]=1)=O.O.O.O.C([O-])(=O)C.[Na+]>>[NH2:5][C:6]1[S:7][CH:8]=[C:9]([C:11](=[N:29][O:30][CH3:31])[C:12]([NH:14][CH:15]2[C:27](=[O:28])[N:17]3[C:18]([C:24]([OH:26])=[O:25])=[C:19]([CH3:23])[CH:20]([CH3:22])[S:21][C@H:16]23)=[O:13])[N:10]=1
Reactant: CON=C(C(=O)NC1C(=O)N2C(C(=O)O)=C(C)C(C)S[C@H]12)c1csc(NC(=O)C(F)(F)F)n1
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: O
Product: CON=C(C(=O)NC1C(=O)N2C(C(=O)O)=C(C)C(C)S[C@H]12)c1csc(N)n1
Temperature: 25 °C
Reaction time: 19 h
Yield: 22.9 %

Procedure:
7-[2-{2-(2,2,2-Trifluoroacetamido)-4-thiazolyl}-2-methoxyiminoacetamido]-2,3-dimethyl-3-cephem-4-carboxylic acid (syn isomer, 0.86 g.) was dissolved in an aqueous solution (9 ml.) containing sodium acetate trihydrate (2.3 g.), and the solution was stirred at room temperature for 19 hours. After removing the insoluble substance from the resultant mixture by filtration, the filtrate was adjusted to around pH 2.5 with 10% hydrochloric acid under ice-cooling. The precipitates were collected by filtration, washed with water and dried to give 7-{2-(2-amino-4-thiazolyl)-2-methoxyiminoacetamido}-2,3-dimethyl-3-cephem-4-carboxylic acid (syn isomer, 0.16 g.).
Reaction SMILES: I[C:2]1[CH:7]=[CH:6][C:5](/[C:8](/[CH3:15])=[CH:9]/[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Na+].[Na+].[O:22]1[CH:26]=[CH:25][CH:24]=[C:23]1B(O)O>COCCOC.O>[O:22]1[CH:26]=[CH:25][CH:24]=[C:23]1[C:2]1[CH:7]=[CH:6][C:5](/[C:8](/[CH3:15])=[CH:9]/[C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=1
Reactant: CCOC(=O)/C=C(\C)c1ccc(I)cc1
Reactant: OB(O)c1ccco1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: CCOC(=O)/C=C(\C)c1ccc(-c2ccco2)cc1
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
Tetrakis(triphenylphoshine)palladium(0) (0.69 g, 0.60 mmol, 6 mol %) was added, under nitrogen, to a stirred solution of (E)-ethyl 3-(4-iodophenyl)-but-2-enoate (3.16 g, 10.0 mmol) in DME (100 ml), and the resulting orange coloured solution stirred at room temperature for 10 min. Aqueous 2M sodium carbonate (30.0 ml, 60.0 mmol) was then added, the mixture stirred for 10 min, then furan-2-boronic acid (2.25 g, 20.11 mmol) was added, and the reaction mixture heated to 80° C. for 20 h, under reflux. The reaction mixture was cooled, diluted with water (100 ml) and the products extracted into ethyl acetate (3×100 ml). The combined organic extracts were washed with brine, dried (MgSO4), and evaporated to give the crude product, which was purified by column chromatography on silica gel (3% diethyl ether in n-heptane eluent) to give the product, (E)-ethyl 3-(4-furan-2-yl-phenyl)-but-2-enoate as an off-white solid; 2.46 g (96%).
Reaction SMILES: [CH3:1][C:2]([CH3:38])([CH3:37])[C:3](=[O:36])[CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]([C:17]2[O:18][C:19]3[CH:25]=[CH:24][C:23]([C:26]([NH:28][C:29]([CH3:34])([CH3:33])[C:30]([OH:32])=[O:31])=[O:27])=[CH:22][C:20]=3[CH:21]=2)([CH2:15][CH3:16])[CH2:13][CH3:14])=[CH:8][C:7]=1[CH3:35].[BH4-].[Na+]>C1COCC1>[CH2:13]([C:12]([C:17]1[O:18][C:19]2[CH:25]=[CH:24][C:23]([C:26]([NH:28][C:29]([CH3:33])([CH3:34])[C:30]([OH:32])=[O:31])=[O:27])=[CH:22][C:20]=2[CH:21]=1)([C:9]1[CH:10]=[CH:11][C:6]([O:5][CH2:4][CH:3]([OH:36])[C:2]([CH3:38])([CH3:37])[CH3:1])=[C:7]([CH3:35])[CH:8]=1)[CH2:15][CH3:16])[CH3:14]
Reactant: CCC(CC)(c1ccc(OCC(=O)C(C)(C)C)c(C)c1)c1cc2cc(C(=O)NC(C)(C)C(=O)O)ccc2o1
Agent: [BH4-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCC(CC)(c1ccc(OCC(O)C(C)(C)C)c(C)c1)c1cc2cc(C(=O)NC(C)(C)C(=O)O)ccc2o1
Yield: 95.5 %

Procedure:
2-[(2-{1-[4-(3,3-Dimethyl-2-oxo-butoxy)-3-methyl-phenyl]-1-ethyl-propyl}-benzofuran-5-carbonyl)-amino]-2-methyl-propionic acid (Example 10) (47 mg, 0.090 mmol) in THF (2.0 mL) are reacted with NaBH4 (7 mg, 0.18 mmol) analogous to Example 8 to yield title compound (45 mg, 96%). MS (ES) m/e: 522.3 (M−1), 524.3 (M+1)
Reaction SMILES: Cl.[Cl:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([OH:9])=O)=[CH:5][C:4]=1[O:12][C:13]1[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]2[S:21][CH:22]=[C:23]([CH3:25])[N:24]=2)[CH:14]=1.C(N(CC)CC)C.C(Cl)(=O)OCC.[NH2:39][CH2:40][CH2:41][N:42]1[CH2:46][CH2:45][CH2:44][CH2:43]1>CN(C=O)C>[ClH:2].[Cl:2][C:3]1[CH:11]=[CH:10][C:6]([C:7]([NH:39][CH2:40][CH2:41][N:42]2[CH2:46][CH2:45][CH2:44][CH2:43]2)=[O:9])=[CH:5][C:4]=1[O:12][C:13]1[CH:18]=[CH:17][N:16]=[C:15]([NH:19][C:20]2[S:21][CH:22]=[C:23]([CH3:25])[N:24]=2)[CH:14]=1
Reactant: Cc1csc(Nc2cc(Oc3cc(C(=O)O)ccc3Cl)ccn2)n1
Reactant: NCCN1CCCC1
Agent: CCOC(=O)Cl
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CN(C)C=O
Product: Cc1csc(Nc2cc(Oc3cc(C(=O)NCCN4CCCC4)ccc3Cl)ccn2)n1
Yield: 33.8 %

Procedure:
Following procedure of Example 83, 4-chloro-3-(2-(4-methylthiazol-2-ylamino)pyridin-4-yloxy)benzoic acid hydrochloride (0.1 g, 0.2511 mmol), triethylamine (0.1016 g, 1.004 mmol), DMF (3 mL), added ethyl carbonochloridate (0.02641 mL, 0.2762 mmol), N-(2-aminoethyl)pyrrolidine (0.05734 g, 0.5022 mmol) were reacted to afford 4-chloro-3-(2-(4-methylthiazol-2-ylamino)pyridin-4-yloxy)-N-(2-(pyrrolidin-1-yl)ethyl)benzamide hydrochloride (0.021 g, 15.22% yield) as off white solid. 1H NMR (DMSO) δ 11.26 (bs, 1H), 10.18 (bs, 1H), 8.98 (t, 1H), 8.23 (d, 1H), 7.92 (dd, 1H), 7.89 (d, 1H), 7.83 (d, 1H), 6.58 (m, 3H), 3.61 (m, 4H), 3.31 (q, 2H), 3.02 (m, 2H), 2.21 (d, 3H), 2.00 (m, 2H), 1.86 (m, 2H); Mass spectrum (esi) m/z 458 (100) (M+H—HCl).
Reaction SMILES: [CH3:1][C:2]1[C:3]([N+:16]([O-:18])=[O:17])=[C:4](OS(C(F)(F)F)(=O)=O)[CH:5]=[CH:6][CH:7]=1.[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:21])[CH3:20].C(N(CC)CC)C>C(#N)C>[C:19]([O:23][C:24]([N:26]1[CH2:31][CH2:30][N:29]([C:4]2[CH:5]=[CH:6][CH:7]=[C:2]([CH3:1])[C:3]=2[N+:16]([O-:18])=[O:17])[CH2:28][CH2:27]1)=[O:25])([CH3:22])([CH3:20])[CH3:21]
Reactant: Cc1cccc(OS(=O)(=O)C(F)(F)F)c1[N+](=O)[O-]
Reactant: CC(C)(C)OC(=O)N1CCNCC1
Solvent: CC#N
Solvent: CCN(CC)CC
Product: Cc1cccc(N2CCN(C(=O)OC(C)(C)C)CC2)c1[N+](=O)[O-]
Yield: 37.5 %

Procedure:
Trifluoromethanesulfonic acid 3-methyl-2-nitrophenyl ester (26.7 g, 93.6 mmol), 1-tert-butoxycarbonyl piperazine (17 g, 91.3 mmol) and triethylamine (14 mL, 100 mmol) in 250 mL of acetonitrile was heated under reflux for 25 h. The mixture was concentrated in vacuo, diluted with water and extracted with ether. The ether was washed with aqueous ammonium hydroxide and brine, dried, and evaporated. Purification by silica gel chromatography (10% ethyl acetate-hexane) afforded 11 g of 4-(3-methyl-2-nitrophenyl)-piperazine-1-carboxylic acid tert-butyl ester as a golden solid, m.p. 101-102° C.
Reaction SMILES: [NH2:1][C:2]1[N:7]=[C:6]2[C:8]([CH:11]3[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]3)=[CH:9][NH:10][C:5]2=[CH:4][CH:3]=1.[CH3:18][O:19][C:20]1[CH:28]=[CH:27][CH:26]=[CH:25][C:21]=1[C:22](Cl)=[O:23]>>[CH3:18][O:19][C:20]1[CH:28]=[CH:27][CH:26]=[CH:25][C:21]=1[C:22]([NH:1][C:2]1[N:7]=[C:6]2[C:8]([CH:11]3[CH2:16][CH2:15][N:14]([CH3:17])[CH2:13][CH2:12]3)=[CH:9][NH:10][C:5]2=[CH:4][CH:3]=1)=[O:23]
Reactant: COc1ccccc1C(=O)Cl
Reactant: CN1CCC(c2c[nH]c3ccc(N)nc23)CC1
Product: COc1ccccc1C(=O)Nc1ccc2[nH]cc(C3CCN(C)CC3)c2n1
Yield: 37.4 %

Procedure:
Beginning with 0.010 gm (0.044 mMol) 5-amino-3-(1-methylpiperidin-4-yl)pyrrolo[3,2-b]pyridine and 0.008 mL (0.058 mMol) 2-methoxybenzoyl chloride, 0.006 gm (39%) of the title compound were prepared essentially by the procedure described in Example 7.
Reaction SMILES: C1(N)C=CC(N)=CC=1.C(Cl)(=O)C1C=CC(C([Cl:16])=O)=CC=1.[CH3:21][N:22]1[C:26](=[O:27])[CH2:25]C[CH2:23]1.[Cl-:28].[Cl-].[Ca+2:30]>>[CH3:25][C:26]([N:22]([CH3:23])[CH3:21])=[O:27].[Cl-:16].[Cl-:28].[Ca+2:30]
Reactant: O=C(Cl)c1ccc(C(=O)Cl)cc1
Reactant: CN1CCCC1=O
Agent: Nc1ccc(N)cc1
Agent: [Ca+2]
Agent: [Cl-]
Product: CC(=O)N(C)C

Procedure:
In some embodiments, the present invention is related to a process that produces fiber derived from the polymerization of 5(6)-amino-2-(p-aminophenyl)benzimidazole, para-phenylenediamine, and terephthaloyl dichloride at high solids (7 weight percent or greater) in NMP/CaCl2 or DMAC/CaCl2, isolates the copolymer crumb, dissolves the isolated copolymer crumb in concentrated sulfuric acid to form a liquid crystalline solution, and spins the solution into fibers.
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]([OH:17])[CH:5]=[CH:6][C:7]=1B1OC(C)(C)C(C)(C)O1.[CH3:18][O:19][C:20](=[O:32])[CH2:21][C:22]1[C:30]2[C:25](=[CH:26][CH:27]=[C:28](Br)[CH:29]=2)[NH:24][CH:23]=1.C(=O)([O-])[O-].[K+].[K+].Cl>O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.C(O)C.CN(C=O)C>[CH3:18][O:19][C:20](=[O:32])[CH2:21][C:22]1[C:30]2[C:25](=[CH:26][CH:27]=[C:28]([C:7]3[CH:6]=[CH:5][C:4]([OH:17])=[CH:3][C:2]=3[CH3:1])[CH:29]=2)[NH:24][CH:23]=1
Reactant: Cc1cc(O)ccc1B1OC(C)(C)C(C)(C)O1
Reactant: COC(=O)Cc1c[nH]c2ccc(Br)cc12
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CCO
Solvent: O
Solvent: CN(C)C=O
Product: COC(=O)Cc1c[nH]c2ccc(-c3ccc(O)cc3C)cc12
Temperature: 100 °C
Yield: 59.8 %

Procedure:
A mixture of 3-methyl-4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenol (287 mg, 1.22 mmol), (5-bromo-1H-indol-3-yl)-acetic acid methyl ester (273 mg, 1.02 mmol), tetrakis(triphenylphosphine)palladium(0) (57 mg, 0.046 mmol), DMF (2.7 mL), ethanol (1.34 mL) and 2M aqueous potassium carbonate (1.34 mL) is heated to 100° C. for 16 hours. The reaction is cooled to room temperature and diluted with water and acidified with 1 N HCl. The resulting solution is extracted with ethyl acetate. The combined organic layers are dried over anhydrous magnesium sulfate and concentrated. The residue is dissolved in methanol (6 mL) and trimethylsilyldiazomethane (2.0 M solution in hexanes, approximately 4 mL) is added over approximately two minutes at room temperature. The yellow mixture is concentrated and the residue is purified via radial chromatography eluting with a gradient of 20 to 50% ethyl acetate/heptane and crystallized from CH2Cl2/heptane to give the title compound (180 mg, 60%). ES/MS m/e 296.1 (M+1).
Reaction SMILES: C(N(CC)CC)C.Cl.[CH3:9][NH:10][O:11][CH3:12].[C:13](Cl)(=[O:20])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19].O>C(Cl)Cl>[CH3:9][N:10]([O:11][CH3:12])[C:13](=[O:20])[CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH3:19]
Reactant: CNOC
Reactant: CCCCCCC(=O)Cl
Agent: Cl
Solvent: O
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CCCCCCC(=O)N(C)OC
Reaction time: 1 h
Yield: 88.8 %

Procedure:
Triethylamine (19.6 g, 194 mmol) was added dropwise to a suspension of N,O-dimethylhydroxylamine hydrochloride (6.93 g, 71 mmol) in anhydrous CH2Cl2 at 0° C. Heptanoylchloride (9.60 g, 65 mmol) was then added dropwise and the reaction was stirred 1 hour. The crude product mixture was poured into water and the separated aqueous phase was extracted with CH2Cl2. The combined organic layers was washed with aq. HCl, sat. NaHCO3, brine, dried (Na2SO4), and concentrated in vacuo to give 10 g (89%) N-methyl-N-methoxyheptanamide as a yellow oil.
Reaction SMILES: C([O:8][C:9]1[C:14]2[NH:15][C:16](=[O:19])[CH2:17][O:18][C:13]=2[C:12]([C:20](=[O:24])[CH:21](O)O)=[CH:11][CH:10]=1)C1C=CC=CC=1.[O:25]([CH2:32][C:33]1([NH2:36])[CH2:35][CH2:34]1)[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1.FC(F)(F)C([O-])=O>>[OH:8][C:9]1[C:14]2[NH:15][C:16](=[O:19])[CH2:17][O:18][C:13]=2[C:12]([CH:20]([OH:24])[CH2:21][NH:36][C:33]2([CH2:32][O:25][C:26]3[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=3)[CH2:35][CH2:34]2)=[CH:11][CH:10]=1
Reactant: NC1(COc2ccccc2)CC1
Reactant: O=C1COc2c(C(=O)C(O)O)ccc(OCc3ccccc3)c2N1
Agent: O=C([O-])C(F)(F)F
Product: O=C1COc2c(C(O)CNC3(COc4ccccc4)CC3)ccc(O)c2N1

Procedure:
Prepared according to general method 3 from 329 mg (1 mmol) 5-benzyloxy-8-(2,2-dihydroxy-acetyl)-4H-benzo[1,4]oxazin-3-one and 163 mg (1 mmol) 1-phenoxymethyl-cyclopropylamine. Yield: 26 mg (5%, trifluoroacetate); mass spectroscopy: [M+H]+=371.
Reaction SMILES: [OH:1][C:2]1[C:7]([O:8][CH3:9])=[CH:6][N:5]=[C:4]([CH2:10][N:11]2C(=O)C3C(=CC=CC=3)C2=O)[N:3]=1.NN>CCO>[NH2:11][CH2:10][C:4]1[N:3]=[C:2]([OH:1])[C:7]([O:8][CH3:9])=[CH:6][N:5]=1
Reactant: COc1cnc(CN2C(=O)c3ccccc3C2=O)nc1O
Agent: NN
Solvent: CCO
Product: COc1cnc(CN)nc1O

Procedure:
The 2-(4-Hydroxy-5-methoxy-pyrimidin-2-ylmethyl)-isoindole-1,3-dione (50 mg, 0.18 mmol) is suspended in EtOH (2 mL) and to which NH2NH2 (0.5 mL) is added and the mixture is stirred till no starting material left. The precipitate is filtered and the filtrate is concentrated to provide the desired product, which is used directly without further treatment. MS (ESI): 156 (M+1)+1.
Reaction SMILES: Br[C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[O:11][CH3:12].B1([C:19]2[CH:24]=[CH:23][CH:22]=[N:21][CH:20]=2)OCCCO1>>[CH3:12][O:11][C:3]1[CH:4]=[CH:5][C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=1[C:19]1[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=1
Reactant: COc1ccc([N+](=O)[O-])cc1Br
Reactant: c1cncc(B2OCCCO2)c1
Product: COc1ccc([N+](=O)[O-])cc1-c1cccnc1
Yield: 76.1 %

Procedure:
2-Bromo-4-nitroanisole (3.0 g, 12.9 mmol) was reacted with pyridine-3-boronic acid-1,3-propanediol cyclic ester (2.53 g, 15.5 mmol) over 8 hours, as described in Example 62. The resulting crude residue was purified by column chromatography on silica, using 60-70% diethyl ether in dichloromethane as the eluent, to yield 3-(2-methoxy-5-nitrophenyl)pyridine (2.26 g, 85%): δH (360 MHz, d6-DMSO) 3.94 (3H, s), 7.39 (1H, d, J 9.2), 7.50 (1H, dd, J 7.9 and 4.8), 7.97 (1H, dt, J 8.0 and 1.9), 8.19 (1H, d, J 2.8), 8.33 (1H, dd, J 9.2 and 2.8), 8.57-8.64 (1H, m), 8.74 (1H, d, J 1.9).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:8]=[CH:9][C:10]=1[O:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])[C:5](Cl)=[O:6].[N:26]1[CH:31]=[CH:30][CH:29]=[CH:28][C:27]=1[CH2:32][NH:33][C:34](=[O:36])[CH3:35].[H-].[Na+]>O1CCCC1>[C:34]([N:33]([CH2:32][C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][N:26]=1)[C:5](=[O:6])[C:4]1[CH:8]=[CH:9][C:10]([O:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH3:25])=[C:2]([Cl:1])[CH:3]=1)(=[O:36])[CH3:35]
Reactant: CC(=O)NCc1ccccn1
Reactant: CCCCCCCCCCCCCCOc1ccc(C(=O)Cl)cc1Cl
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CCCCCCCCCCCCCCOc1ccc(C(=O)N(Cc2ccccn2)C(C)=O)cc1Cl

Procedure:
The title compound is prepared by the procedure of Example 27 using 1.31 g of product from Example 38, 0.535 g of product from Example 12, 0.171 g of washed 50% sodium hydride and 12 ml of tetrahydrofuran. The residue is purified by column chromatography (silica gel:35% ethyl acetate/hexane) to give 0.067 g of product as a yellow oil.
Reaction SMILES: [NH2:1][C:2]1[CH2:7][C:6]([CH3:9])([CH3:8])[CH2:5][C:4](=[O:10])[CH:3]=1.CO[CH:13](OC)[C:14]1[CH:19]=[CH:18][C:17]([Cl:20])=[C:16]([S:21]([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)(=[O:23])=[O:22])[CH:15]=1>>[C:24]1([S:21]([C:16]2[CH:15]=[C:14]([CH:13]3[C:3]4[C:4](=[O:10])[CH2:5][C:6]([CH3:9])([CH3:8])[CH2:7][C:2]=4[NH:1][C:2]4[CH2:7][C:6]([CH3:9])([CH3:8])[CH2:5][C:4](=[O:10])[C:3]3=4)[CH:19]=[CH:18][C:17]=2[Cl:20])(=[O:22])=[O:23])[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=1
Reactant: CC1(C)CC(=O)C=C(N)C1
Reactant: COC(OC)c1ccc(Cl)c(S(=O)(=O)c2ccccc2)c1
Product: CC1(C)CC(=O)C2=C(C1)NC1=C(C(=O)CC(C)(C)C1)C2c1ccc(Cl)c(S(=O)(=O)c2ccccc2)c1

Procedure:
Reaction of 3-amino-5,5-dimethyl-2-cyclohexen-1-one with 4-chloro-3-phenylsulphonylbenzaldehyde dimethyl acetal in an analogous manner to that described in Example 1 gave 9-[3-benzenesulphonyl-4-chlorophenyl]-3,4,6,7,9,10-hexahydro-3,3,6,6-tetramethyl-1,8(2H,5H)-acridinedione. Crystallization from dimethylformamide/water gave a yellow crystalline solid of melting point 252-254° C. (decomposition).