Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:16][O:15][NH:14][C:13]1=[O:17])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:19]1([C:29]([O:31][CH2:32][C:33]2[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[CH:35][CH:34]=2)=[O:30])[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[C:21](=[O:28])[O:20]1.C(N(CC)CC)C>ClCCl>[CH2:1]([O:8][C:9]([NH:11][C@H:12]1[CH2:16][O:15][N:14]([C:19]2([C:29]([O:31][CH2:32][C:33]3[CH:38]=[CH:37][C:36]([N+:39]([O-:41])=[O:40])=[CH:35][CH:34]=3)=[O:30])[C:27]3[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:21](=[O:28])[O:20]2)[C:13]1=[O:17])=[O:10])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(N[C@H]1CONC1=O)OCc1ccccc1
Reactant: O=C1OC(Cl)(C(=O)OCc2ccc([N+](=O)[O-])cc2)c2ccccc21
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: O=C(N[C@H]1CON(C2(C(=O)OCc3ccc([N+](=O)[O-])cc3)OC(=O)c3ccccc32)C1=O)OCc1ccccc1
Yield: 64.1 %

Procedure:
In 5 ml of dichloromethane were dissolved 236 mg of (4S)-4-benzyloxycarbonylamino-3-isoxazolidinone and 347 mg of Compound (98). To the solution was added, under ice-cooling, 0.14 ml of triethylamine, and the mixture was stirred for 30 minutes. The solvent was evaporated off. To the residue was added ethyl acetate, which was washed with water and an aqueous saline solution. The organic layer was dried, then the solvent was evaporated off. The residue was subjected to a column chromatography using Florisil, followed by elution with hexane--ethyl acetate (2:1→1:1) to give 350 mg of the subject Compound (99) as a pale yellow oily product.
Reaction SMILES: [NH2:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8]C)=[O:7])=[CH:4][C:3]=1[F:12].Cl[CH2:14][CH2:15][CH2:16][S:17](Cl)(=[O:19])=[O:18]>>[O:18]=[S:17]1(=[O:19])[CH2:16][CH2:15][CH2:14][N:1]1[C:2]1[CH:11]=[CH:10][C:5]([C:6]([OH:8])=[O:7])=[CH:4][C:3]=1[F:12]
Reactant: O=S(=O)(Cl)CCCCl
Reactant: COC(=O)c1ccc(N)c(F)c1
Product: O=C(O)c1ccc(N2CCCS2(=O)=O)c(F)c1

Procedure:
Using methyl 4-amino-3-fluorobenzoate (1.12 g) and 3-chloropropane-1-sulfonyl chloride (1.06 mL) and by the reaction and treatment in the same manner as in Preparation Example 16, the title compound (1.04 g) was obtained.
Reaction SMILES: Cl.[N+:2]([C:5]1[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=1[NH:11]N)([O-:4])=[O:3].[C:13]([C:16]1[CH:21]=[N:20][CH:19]=[CH:18][N:17]=1)(=O)[CH3:14]>>[N+:2]([C:5]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:6]=1[NH:11][C:13]([C:16]1[CH:21]=[N:20][CH:19]=[CH:18][N:17]=1)=[CH:14]2)([O-:4])=[O:3]
Reactant: NNc1ccccc1[N+](=O)[O-]
Reactant: CC(=O)c1cnccn1
Agent: Cl
Product: O=[N+]([O-])c1cccc2cc(-c3cnccn3)[nH]c12
Yield: 13 %

Procedure:
2-Nitrophenylhydrazine hydrochloride (3.1 g, 16 mmol) and 2-acetylpyrazine (2.0 ml, 16 mmol) were reacted according to the same procedures as Preparations 4 to 5 to give the title compound (0.5 g, Yield 13%).
Reaction SMILES: [CH3:1][C:2]1[C:6]([C:7](=[O:17])[CH2:8][CH2:9][CH2:10][C:11]2[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=2)=[C:5]([C:18]2[CH:23]=[CH:22][C:21]([C:24]3[CH:29]=[CH:28][C:27]([C:30]4([C:33]([OH:35])=[O:34])[CH2:32][CH2:31]4)=[CH:26][CH:25]=3)=[CH:20][CH:19]=2)[O:4][N:3]=1.[CH3:36][Mg]I>>[OH:17][C:7]([C:6]1[C:2]([CH3:1])=[N:3][O:4][C:5]=1[C:18]1[CH:23]=[CH:22][C:21]([C:24]2[CH:25]=[CH:26][C:27]([C:30]3([C:33]([OH:35])=[O:34])[CH2:32][CH2:31]3)=[CH:28][CH:29]=2)=[CH:20][CH:19]=1)([CH3:36])[CH2:8][CH2:9][CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1
Reactant: C[Mg]I
Reactant: Cc1noc(-c2ccc(-c3ccc(C4(C(=O)O)CC4)cc3)cc2)c1C(=O)CCCc1ccccc1
Product: Cc1noc(-c2ccc(-c3ccc(C4(C(=O)O)CC4)cc3)cc2)c1C(C)(O)CCCc1ccccc1

Procedure:
Prepared according to the procedure described in Example 35, Step 3, using 1-{4′-[3-methyl-4-(4-phenyl-butyryl)-isoxazol-5-yl]-biphenyl-4-yl}-cyclopropanecarboxylic acid and methylmagnesium iodide.
Reaction SMILES: [N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:15]=[CH:14][C:10]([C:11](O)=[O:12])=[CH:9][CH:8]=2)[CH:2]=1.S(Cl)([Cl:18])=O>>[N:1]1[CH:6]=[CH:5][CH:4]=[C:3]([C:7]2[CH:15]=[CH:14][C:10]([C:11]([Cl:18])=[O:12])=[CH:9][CH:8]=2)[CH:2]=1
Reactant: O=S(Cl)Cl
Reactant: O=C(O)c1ccc(-c2cccnc2)cc1
Product: O=C(Cl)c1ccc(-c2cccnc2)cc1
Temperature: 70 °C
Reaction time: 8 h

Procedure:
To a solution of 4-boronobenzoic acid (4.15 g, 25 mmol) and 3-bromopyridine (4.3 g, 27.5 mmol) in acetonitrile (60 mL) and water (60 mL), potassium carbonate (13.8 g, 100 mmol), bis(triphenylphosphine)palladium(II) chloride (1.75 g, 2.5 mmol) was added. The mixture was degassed and purged withed nitrogen. The mixture was stirred under reflux for 24 hours. Then the hot suspension was filtered and concentrated to half of the original volume and washed with dichloromethane. The aquatic phase was adjusted to pH=3 with hydrochloric acid (1 M) and filtrated, washed with water. The residue was dried in vacuum to obtain 4 g of white solid of 4-(pyridin-3-yl)benzoic acid. (Yield: 80%. LC-MS (ESI) m/z: 200 (M+1)+). Thionyl chloride (10 ml) was added to 4-(pyridin-3-yl)benzoic acid (4 g, 20 mmol) and the mixture was stirred at 70° C. overnight. The solvent was evaporated under reduced pressure and the residue was dried in vacuum. 4.5 g of crude 4-(pyridin-3-yl)benzoyl chloride was obtained. To a solution of methyl 3-amino-2-hydroxybenzoate (2.9 g, 17 mmol) and pyridine (4 g, 52 mmol) in toluene (50 ml) were added 4-(pyridin-3-yl)benzoyl chloride (4.5 g, 20.4 mmol) portion-wise at 0° C. and then stirred at 70° C. for 4 h. The resulting mixture was extracted with ethyl acetate (100 mL×4), the organic phase was washed with water and saturated sodium bicarbonate, dried with anhydrous sodium sulfate and evaporated under reduced pressure to obtain methyl 2-hydroxy-3-(4-(pyridine-3-yl)enzamido)benzoate as a yellow solid (5 g, yield 85%). LC-MS (ESI) m/z: 349 (M+1)+.
Reaction SMILES: [NH2:1][CH2:2][C:3]1[C:4](=[O:11])[NH:5][C:6]([CH3:10])=[CH:7][C:8]=1[CH3:9].[C:12]1([S:18]([N:21]2[C:29]3[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=3)[C:23]([C:30](O)=[O:31])=[CH:22]2)(=[O:20])=[O:19])[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1.F[P-](F)(F)(F)(F)F.N1(OC(N(C)C)=[N+](C)C)C2N=CC=CC=2N=N1.C(N(CC)CC)C>ClCCl>[CH3:9][C:8]1[CH:7]=[C:6]([CH3:10])[NH:5][C:4](=[O:11])[C:3]=1[CH2:2][NH:1][C:30]([C:23]1[C:24]2[C:29](=[CH:28][CH:27]=[CH:26][CH:25]=2)[N:21]([S:18]([C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=2)(=[O:19])=[O:20])[CH:22]=1)=[O:31]
Reactant: Cc1cc(C)c(CN)c(=O)[nH]1
Reactant: O=C(O)c1cn(S(=O)(=O)c2ccccc2)c2ccccc12
Agent: CN(C)C(On1nnc2cccnc21)=[N+](C)C
Agent: F[P-](F)(F)(F)(F)F
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: Cc1cc(C)c(CNC(=O)c2cn(S(=O)(=O)c3ccccc3)c3ccccc23)c(=O)[nH]1
Temperature: 25 °C
Reaction time: 15 h
Yield: 27.6 %

Procedure:
A mixture of 3-(aminomethyl)-4,6-dimethylpyridin-2(1H)-one (100 mg, 0.65 mmol), 1-(phenylsulfonyl)-1H-indole-3-carboxylic acid (196 mg, 0.65 mmol), O-(7-azabenzotriazole-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (319 mg, 0.84 mmol) and triethylamine (98 mg, 0.97 mmol) in anhydrous dichloromethane (10 mL) was stirred at room temperature for 15 hours. Then the mixture was filtered and the solid was washed with water (10 mL), methanol (10 mL) and dichloromethane (10 mL) in turns to give N-((4,6-dimethyl-2-oxo-1,2-dihydropyridin-3-yl)methyl)-1-(phenylsulfonyl)-1H-indole-3-carboxamide as a white solid (78 mg, 28%). LRMS (M+H+) m/z: calcd 435.13. found 435.
Reaction SMILES: S(Cl)(Cl)=O.[C:5]([CH2:8][CH2:9][CH2:10]/[CH:11]=[CH:12]\[C@@H:13]1[CH2:17][C@@H:16]([NH:18][S:19]([C:22]2[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=2)(=[O:21])=[O:20])[CH2:15][N:14]1[S:29]([C:32]1[CH:37]=[CH:36][C:35]([Cl:38])=[CH:34][CH:33]=1)(=[O:31])=[O:30])([OH:7])=[O:6].[CH3:39]O>>[Cl:38][C:35]1[CH:34]=[CH:33][C:32]([S:29]([N:14]2[CH2:15][C@H:16]([NH:18][S:19]([C:22]3[CH:27]=[CH:26][C:25]([Cl:28])=[CH:24][CH:23]=3)(=[O:21])=[O:20])[CH2:17][C@H:13]2/[CH:12]=[CH:11]\[CH2:10][CH2:9][CH2:8][C:5]([O:7][CH3:39])=[O:6])(=[O:31])=[O:30])=[CH:37][CH:36]=1
Reactant: O=C(O)CCC/C=C\[C@@H]1C[C@@H](NS(=O)(=O)c2ccc(Cl)cc2)CN1S(=O)(=O)c1ccc(Cl)cc1
Reactant: CO
Solvent: O=S(Cl)Cl
Product: COC(=O)CCC/C=C\[C@@H]1C[C@@H](NS(=O)(=O)c2ccc(Cl)cc2)CN1S(=O)(=O)c1ccc(Cl)cc1
Reaction time: 0.5 h

Procedure:
Thionyl chloride (0.32 ml) was added to methanol (20 ml) at -78° C. and the solution was stirred at the same temperature for 30 minutes. To the solution was added (2S,4R)-2-[(Z)-5-carboxy-1-pentenyl]-1-(4-chlorophenylsulfonyl)-4-(4-chlorophenylsulfonylamino)pyrrolidine (2.0 g) and the mixture was stirred at room temperature for 2 hours. After removal of the solvent by evaporation in vacuo, the residue was dissolved in chloroform and washed successively with saturated aqueous sodium bicarbonate and brine. The organic layer was dried over magnesium sulfate and the solvent was evaporated in vacuo. The residue was solidified with ether to give (2S,4R)-1-(4-chlorophenylsulfonyl)-4-(4-chlorophenylsulfonylamino)-2-[(Z)-methoxycarbonyl-1-pentenyl]pyrrolidine (2.0 g).
Reaction SMILES: [C:1]1([C:7]2[N:8]=[N:9][CH:10]=[C:11]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[C:12]=2[C:13]2[O:14][CH:15]=[C:16]([C:18](=[O:20])[CH3:19])[N:17]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[BH4-].[Na+]>CO>[C:1]1([C:7]2[N:8]=[N:9][CH:10]=[C:11]([C:21]3[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=3)[C:12]=2[C:13]2[O:14][CH:15]=[C:16]([CH:18]([OH:20])[CH3:19])[N:17]=2)[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1
Reactant: CC(=O)c1coc(-c2c(-c3ccccc3)cnnc2-c2ccccc2)n1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: CC(O)c1coc(-c2c(-c3ccccc3)cnnc2-c2ccccc2)n1
Temperature: 25 °C
Reaction time: 2 h
Yield: 99.3 %

Procedure:
To a solution of 1-(2-(3,5-diphenylpyridazin-4-yl)oxazol-4-yl)ethanone (30 mg, 0.088 mmol) in methanol (4 mL), NaBH4 (8.4 mg, 0.176 mmol) was added at 0° C. and the reaction mixture was warmed to rt and stirred for 2 h. The reaction mixture was quenched in ice cold water, extracted with ethyl acetate (25 mL). The organic layer was washed with brine (1×5 mL), dried over Na2SO4 and concentrated under reduced pressure to obtain the crude product which was carried further without any purification gave 1-(2-(3,5-diphenylpyridazin-4-yl)oxazol-4-yl)ethanol (30 mg)
Reaction SMILES: [F:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][S:7]([CH2:10][C:11](O)=O)(=[O:9])=[O:8])=[CH:4][CH:3]=1.[F:16][C:17]1[CH:24]=[CH:23][C:20](C=O)=[CH:19][CH:18]=1>>[F:1][C:2]1[CH:15]=[CH:14][C:5]([CH2:6][S:7](/[CH:10]=[CH:11]/[C:20]2[CH:23]=[CH:24][C:17]([F:16])=[CH:18][CH:19]=2)(=[O:9])=[O:8])=[CH:4][CH:3]=1
Reactant: O=C(O)CS(=O)(=O)Cc1ccc(F)cc1
Reactant: O=Cc1ccc(F)cc1
Product: O=S(=O)(/C=C/c1ccc(F)cc1)Cc1ccc(F)cc1
Yield: 73 %

Procedure:
A solution of 4-fluorobenzyl sulfonylacetic acid (0.01 mol) and 4-fluorobenzaldehyde (0.01 mol) was subjected to Procedure 1, Part B. The title compound was obtained in 73% yield.
Reaction SMILES: C[C:2]1[CH:9]=[C:8]([NH:10][C:11]2[N:16]=[C:15]([NH:17][C:18]3[C:23]([CH3:24])=[CH:22][C:21]([Br:25])=[CH:20][C:19]=3[CH3:26])[C:14]([N+:27]([O-:29])=[O:28])=[C:13]([CH3:30])[N:12]=2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].C(O[CH:36](N(C)C)[N:37]([CH3:39])[CH3:38])(C)(C)C>CN(C=O)C>[Br:25][C:21]1[CH:22]=[C:23]([CH3:24])[C:18]([NH:17][C:15]2[C:14]([N+:27]([O-:29])=[O:28])=[C:13](/[CH:30]=[CH:36]/[N:37]([CH3:39])[CH3:38])[N:12]=[C:11]([NH:10][C:8]3[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[CH:2][CH:9]=3)[N:16]=2)=[C:19]([CH3:26])[CH:20]=1
Reactant: Cc1cc(Nc2nc(C)c([N+](=O)[O-])c(Nc3c(C)cc(Br)cc3C)n2)ccc1C#N
Reactant: CN(C)C(OC(C)(C)C)N(C)C
Solvent: CN(C)C=O
Product: Cc1cc(Br)cc(C)c1Nc1nc(Nc2ccc(C#N)cc2)nc(/C=C/N(C)C)c1[N+](=O)[O-]
Temperature: 60 °C
Reaction time: 8 h
Yield: 66.5 %

Procedure:
A dried flask under argon was charged with methyl 4-(4-(4-bromo-2,6-dimethylphenylamino)-6-methyl-5-nitropyrimidin-2-ylamino)benzonitrile (4.3 g, 9.5 mmol) dissolved in anhydrous DMF (95 ml) followed by tert-butoxybis(dimethylamino)methane (2.4 ml, 11.4 mmol). The reaction mixture was heated to 60° C. and stirred overnight under argon. Upon completion the reaction was cooled to ambient temperature, concentrated to half volume, and quenched with H2O (100 ml). The aqueous solution was extracted with ethyl acetate (3×70 ml) and the collected organic fractions were washed with brine (100 ml), dried with MgSO4, filtered and concentrated. Silica gel chromatography (ethyl acetate:Hexanes=50:50) yielded (E)-4-(4-(4-bromo-2,6-dimethylphenylamino)-6-(2-(dimethylamino)vinyl)-5-nitropyrimidin-2-ylamino)benzonitrile (3.21 g, 67%) as a brown solid. m/z=508 [M+1].
Reaction SMILES: [OH:1][C:2]12[CH2:11][CH:6]3[CH2:7][CH:8]([CH2:10][C:4]([NH2:12])([CH2:5]3)[CH2:3]1)[CH2:9]2.C(N(CC)CC)C.[C:20]1([C:26](Cl)([C:33]2[CH:38]=[CH:37][CH:36]=[CH:35][CH:34]=2)[C:27]2[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1>ClCCl>[C:26]([NH:12][C:4]12[CH2:10][CH:8]3[CH2:7][CH:6]([CH2:11][C:2]([OH:1])([CH2:9]3)[CH2:3]1)[CH2:5]2)([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)([C:33]1[CH:34]=[CH:35][CH:36]=[CH:37][CH:38]=1)[C:27]1[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=1
Reactant: ClC(c1ccccc1)(c1ccccc1)c1ccccc1
Reactant: NC12CC3CC(C1)CC(O)(C3)C2
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: OC12CC3CC(C1)CC(NC(c1ccccc1)(c1ccccc1)c1ccccc1)(C3)C2
Temperature: 25 °C
Reaction time: 0.17 h

Procedure:
To 3-hydroxytricyclo[3.3.1.13,7 ]decan- 1-amine (5 g; 0.03 mole) dissolved in dichloromethane (140 ml) with gentle heating is added triethylamine (6 g; 0.06 mole) and cooled in an ice bath. Triphenylmethyl chloride (8.30 g; 0.03 mole) in CH2Cl2 (10 ml) is added all at once. The reaction is stirred in an ice bath for 10 minutes, warmed to room temperature and then refluxed for 3 hours. The reaction is then filtered and the filtrate evaporated to dryness. The reaction products are separated on HPLC, using 15% ethyl acetate/hexane and the product is then recrystallized from ethyl acetate/pet. ether to give N-trityl-3-hydroxytricyclo-[3.3.1.13,7 ]decan-1-amine (m.p. 184°-186° C.) which is used directly in step C.
Reaction SMILES: [F:1][C:2]1[CH:3]=[C:4]([C:8]2([C:14](O)=[O:15])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1.[H-].[Al+3].[Li+].[H-].[H-].[H-]>C1COCC1>[F:1][C:2]1[CH:3]=[C:4]([C:8]2([CH2:14][OH:15])[CH2:13][CH2:12][CH2:11][CH2:10][CH2:9]2)[CH:5]=[CH:6][CH:7]=1
Reactant: O=C(O)C1(c2cccc(F)c2)CCCCC1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: OCC1(c2cccc(F)c2)CCCCC1
Temperature: 0 °C
Reaction time: 1.5 h
Yield: 90 %

Procedure:
To a solution of 1-(3-fluorophenyl)cyclohexanecarboxylic acid (0.8 g, 3.60 mmol) in THF (10 mL) at 0° C. was added 2M lithium aluminum hydride (2.500 mL, 5.0 mmol) in THF dropwise and the mixture was stirred at 0° C. for 1.5 hrs. The reaction was quenched with Na2SO4.10H2O and stirred for 0.5 hrs. The reaction mixture was filtered through Celite and washed with EtOAc. The filtrate was washed with 1N HCl followed by 1N NaOH and brine. The EtOAc layer was dried over Na2SO4 and evaporated to give (1-(3-fluorophenyl)cyclohexyl)methanol (675 mg, 3.24 mmol, 90% yield) as an oil. 1H NMR (400 MHz, CCl3D) δ ppm 7.33 (1H, td, J=8.02, 6.37 Hz), 7.16 (1H, d, J=7.91 Hz), 7.09 (1H, dt, J=11.26, 2.17 Hz), 6.89-6.96 (1H, m), 3.50 (2H, s), 2.10 (2H, dd, J=12.85, 3.84 Hz), 1.30-1.66 (9H, m).
Reaction SMILES: [CH2:1]([NH2:8])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl[C:10]1[N:15]=[C:14]([NH:16][C:17]([C:19]2([C:22]3[CH:32]=[CH:31][C:25]4[O:26][C:27]([F:30])([F:29])[O:28][C:24]=4[CH:23]=3)[CH2:21][CH2:20]2)=[O:18])[CH:13]=[CH:12][C:11]=1[CH3:33]>>[CH2:1]([NH:8][C:10]1[N:15]=[C:14]([NH:16][C:17]([C:19]2([C:22]3[CH:32]=[CH:31][C:25]4[O:26][C:27]([F:30])([F:29])[O:28][C:24]=4[CH:23]=3)[CH2:20][CH2:21]2)=[O:18])[CH:13]=[CH:12][C:11]=1[CH3:33])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NCc1ccccc1
Reactant: Cc1ccc(NC(=O)C2(c3ccc4c(c3)OC(F)(F)O4)CC2)nc1Cl
Product: Cc1ccc(NC(=O)C2(c3ccc4c(c3)OC(F)(F)O4)CC2)nc1NCc1ccccc1

Procedure:
To benzylamine (0.5 mL, 4.6 mmol) was added N-(6-chloro-5-methylpyridin-2-yl)-1-(2,2-difluorobenzo[d][1,3]dioxol-5-yl)cyclopropanecarboxamide (37 mg, 0.1 mmol and the reaction mixture was irradiated in the microwave at 170° C. for 60 minutes. The crude product purified by reverse-phase preparative liquid chromatography utilizing a gradient of 0-99% acetonitrile in water containing 0.05% trifluoracetic acid to yield the pure product. ESI-MS m/z calc. 437.4, found 438.3 (M+1)+; retention time 1.83 minutes.
Reaction SMILES: Cl[CH2:2][C:3]([CH:5]1[CH2:9][CH2:8][CH2:7][S:6]1)=[O:4].[SH:10][C@H:11]1[NH:14][C:13](=[O:15])[C@H:12]1[NH:16][C:17](=[O:26])[CH2:18][O:19][C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C.C(OCC)(=O)C>[O:19]([CH2:18][C:17]([NH:16][C@H:12]1[C@@H:11]([S:10][CH2:2][C:3]([CH:5]2[CH2:9][CH2:8][CH2:7][S:6]2)=[O:4])[NH:14][C:13]1=[O:15])=[O:26])[C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1
Reactant: O=C(COc1ccccc1)N[C@@H]1C(=O)N[C@@H]1S
Reactant: O=C(CCl)C1CCCS1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Solvent: CN(C)C=O
Product: O=C(COc1ccccc1)N[C@@H]1C(=O)N[C@@H]1SCC(=O)C1CCCS1
Yield: 72.6 %

Procedure:
(RS)-2-Chloroacetyltetrahydrothiophene (2.50 g), (3R,4R)-4-mercapto-3-phenoxyacetamidoazetidin-2-one (4.60 g) and potassium carbonate (2.52 g) in DMF (30 ml) were stirred at room temperature for 2.5 h. T.l.c. analysis (ethyl acetate) showed completion of the reaction. The reaction mixture was diluted with ethyl acetate, washed with water (3×), brine and then dried. The solvent was evaporated and the residue flash chromatographed on silica gel eluting with 80% ethyl acetate/hexane to give the title compound as a pale yellow solid (4.194 g, 73%); m.p. 123° C., ethyl acetate/hexane; (Found: C, 53.51; H, 5.00; N, 7.39; S, 17.06%. C17H20N2O4S2 requires C, 53.66; H, 5.30; N, 7.36; S, 16.85%); νmax (CH2Cl2) 3405, 1785 and 1695 cm-1 ; δH (CDCl3), 1.81-1.95 (1H, m), 2.01-2.12 (2H, m), 2.28-2.42 (1H, m), 2.88 (2H, t, J 6.5 Hz), 3.39 and 3.56 with 3.39 and 3.45 (2H, 2 ABq, J 5.9 Hz), 4.07 and 4.09 (1H, 2 t, J 3.8 and 3.7 Hz), 4.58 (2H, s), 5.00 and 5.04 (1H, 2d, J 4.6 Hz), 5.58 and 5.60 (1H, 2 dd's,J 4.6, 9.2 Hz), 6.55 and 6.64 (1H, 2 br s), 6.94-7.07 (3H, m), 7.27-7.36 (2H, m), and 7.46 and 7.47 (1H, 2 br d, J 9.2 Hz).
Reaction SMILES: CO[CH:3](OC)[CH:4]([NH:6][C:7]1[CH2:13][N:12]=[C:11]([C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=2[Cl:20])[C:10]2[CH:21]=[C:22]([Cl:25])[CH:23]=[CH:24][C:9]=2[N:8]=1)[CH3:5]>[Ti](Cl)(Cl)(Cl)Cl.C(COC)OC>[Cl:25][C:22]1[CH:23]=[CH:24][C:9]2[N:8]3[CH:3]=[C:4]([CH3:5])[N:6]=[C:7]3[CH2:13][N:12]=[C:11]([C:14]3[CH:19]=[CH:18][CH:17]=[CH:16][C:15]=3[Cl:20])[C:10]=2[CH:21]=1
Reactant: COC(OC)C(C)NC1=Nc2ccc(Cl)cc2C(c2ccccc2Cl)=NC1
Agent: Cl[Ti](Cl)(Cl)Cl
Solvent: COCCOC
Product: Cc1cn2c(n1)CN=C(c1ccccc1Cl)c1cc(Cl)ccc1-2
Temperature: 25 °C

Procedure:
A sample of 2-[[7-chloro-5-(o-chlorophenyl)-3H-1,4-benzodiazepin-2-yl]amino]propionaldehyde dimethyl acetal (2.03 g., 5.00 mmol), dissolved in 60 ml. of monoglyme, is treated with 0.75 ml. (1.30 g., 6.85 mmol) of (reagent-grade) titanium tetrachloride. A vigorous reaction takes place and a brown solid precipitates in the reaction flask. The mixture is refluxed under nitrogen for 4 hours. The reaction mixture is cooled to room temperature, poured into 250 ml. of cold 5% aqueous sodium hydroxide and extracted with chloroform (400 ml.). The chloroform layer is washed with brine, dried over anhydrous magnesium sulfate and concentrated in vacuo to a solid. After crystallization 960 mg. of 8-chloro-2-methyl-6-(o-chlorophenyl)-4H-imidazo[1,2-a][1,4]-benzodiazepine of melting point 169.5° -170.5° C. is obtained.
Reaction SMILES: [CH3:1][S:2]SC.[CH:5]1[C:15]2=[C:16]3[C:11](=[CH:12][CH:13]=[CH:14]2)[CH:10]=[CH:9][CH:8]=[C:7]3[CH:6]=1>N1C=CC=CC=1>[CH3:1][S:2][C:6]1[C:7]2=[C:16]3[C:11](=[CH:10][CH:9]=[CH:8]2)[CH:12]=[CH:13][CH:14]=[C:15]3[CH:5]=1
Reactant: C1=Cc2cccc3cccc1c23
Reactant: CSSC
Solvent: c1ccncc1
Product: CSC1=Cc2cccc3cccc1c23
Yield: 76 %

Procedure:
As an example of the benefits that can be realized by use of the two-step procedure, controlled potential electrolysis of dimethyl disulfide in the presence of acenaphthylene in the absence of an organic nucleophilic base resulted in copious polymer formation. But when the same electrolysis procedure was conducted in the additional presence of pyridine, an oxidation-resistant adduct of this invention formed which on eliminative aromatization in the second step resulted in the production of 1-methylthioacenaphthylene in 76% yield using electrochemical reductive elimination.
Reaction SMILES: [CH3:1][N:2]1[CH2:6][C:5](=[O:7])[N:4]([CH3:8])[C:3]1=[NH:9].[Cl:10][C:11]1[CH:12]=[C:13]([N:17]=[C:18]=[O:19])[CH:14]=[CH:15][CH:16]=1>O1CCCC1>[Cl:10][C:11]1[CH:12]=[C:13]([NH:17][C:18]([N:9]=[C:3]2[N:4]([CH3:8])[C:5](=[O:7])[CH2:6][N:2]2[CH3:1])=[O:19])[CH:14]=[CH:15][CH:16]=1
Reactant: O=C=Nc1cccc(Cl)c1
Reactant: CN1CC(=O)N(C)C1=N
Solvent: C1CCOC1
Product: CN1CC(=O)N(C)C1=NC(=O)Nc1cccc(Cl)c1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
A mixture of 6.35 g (0.050 mole) of 1,3-dimethyl-2-iminoimidazolidin-4-one, 7.85 g (0.050 mole) of 3-chlorophenylisocyanate and 75 ml of dry tetrahydrofuran is stirred at room temperature for four hours. The solution is evaporated in vacuo and the residue is crystallized from acetonitrile. Two recrystallizations from acetonitrile - ether gives pure product, 1-(3-chlorophenyl)-3-(1,3-dimethyl-4-oxo-2-imidazolidinylidene)urea, m.p. 134°-137° C.
Reaction SMILES: FC(F)(F)S(O[C:7]1[C:11]2[C:12]([O:16][CH3:17])=[N:13][CH:14]=[CH:15][C:10]=2[N:9]([CH:18]2[CH2:23][CH2:22][CH2:21][CH2:20][CH2:19]2)[N:8]=1)(=O)=O.CC1(C)C(C)(C)OB([C:34]2[CH:39]=[CH:38][C:37]([S:40]([NH2:43])(=[O:42])=[O:41])=[CH:36][CH:35]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].O>COCCOC.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>[CH:18]1([N:9]2[C:10]3[CH:15]=[CH:14][N:13]=[C:12]([O:16][CH3:17])[C:11]=3[C:7]([C:34]3[CH:39]=[CH:38][C:37]([S:40]([NH2:43])(=[O:42])=[O:41])=[CH:36][CH:35]=3)=[N:8]2)[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23]1
Reactant: COc1nccc2c1c(OS(=O)(=O)C(F)(F)F)nn2C1CCCCC1
Reactant: CC1(C)OB(c2ccc(S(N)(=O)=O)cc2)OC1(C)C
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: O
Solvent: COCCOC
Product: COc1nccc2c1c(-c1ccc(S(N)(=O)=O)cc1)nn2C1CCCCC1
Yield: 98.2 %

Procedure:
A solution of 1-cyclohexyl-4-methoxy-1H-pyrazolo[4,3-c]pyridin-3-yl trifluoromethanesulfonate (60 mg), 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzenesulfonamide (67 mg), tetrakis(triphenylphosphine)palladium(0) (18 mg) and 2M aqueous sodium carbonate solution (0.40 mL) in DME (10 mL) was stirred under nitrogen atmosphere at 100° C. for 3 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane) to give the title compound (60 mg).
Reaction SMILES: C([O:3][C:4]([C:6]1[C:10]([N+:11]([O-:13])=[O:12])=[CH:9][N:8]([CH2:14][CH2:15][C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][CH:17]=2)[N:7]=1)=O)C.[BH4-].[Na+]>CO>[N+:11]([C:10]1[C:6]([CH2:4][OH:3])=[N:7][N:8]([CH2:14][CH2:15][C:16]2[CH:17]=[CH:18][CH:19]=[CH:20][CH:21]=2)[CH:9]=1)([O-:13])=[O:12]
Reactant: CCOC(=O)c1nn(CCc2ccccc2)cc1[N+](=O)[O-]
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: O=[N+]([O-])c1cn(CCc2ccccc2)nc1CO
Reaction time: 1 h
Yield: 69.7 %

Procedure:
495 mg (1.8 mM) of 4-nitro-1-phenethyl-1H-pyrazole-3-carboxylic acid ethyl ester was dissolved in 5 ml of methyl alcohol, to which 680 mg (18 mM, 13 eq) of sodium borohydride was added dropwise at 0° C., and the resulting mixture was stirred under a nitrogen atmosphere for 1 hour. The solvent was distilled off under reduced pressure, and the resultant was extracted with ethyl acetate and brine. The organic solvent layer was dried over anhydrous sodium sulfate, filtered, and then distilled under reduced pressure. The resulting impure compound was purified by column chromatography (hexane:ethyl acetate=2:1), to obtain 295 mg (66.4%) of the title compound.