Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([NH:10][C:11](=[O:18])OCC(Cl)(Cl)Cl)=[N:7][C:6]=2[CH:19]=1.[C:20]1([C:26]2[N:30]=[C:29]([N:31]3[CH2:36][CH2:35][NH:34][CH2:33][CH2:32]3)[S:28][N:27]=2)[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1.C(N(C(C)C)CC)(C)C.O>CS(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8]([NH:10][C:11]([N:34]3[CH2:35][CH2:36][N:31]([C:29]4[S:28][N:27]=[C:26]([C:20]5[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=5)[N:30]=4)[CH2:32][CH2:33]3)=[O:18])=[N:7][C:6]=2[CH:19]=1
Reactant: O=C(Nc1nc2cc(Cl)ccc2o1)OCC(Cl)(Cl)Cl
Reactant: c1ccc(-c2nsc(N3CCNCC3)n2)cc1
Solvent: CCN(C(C)C)C(C)C
Solvent: O
Solvent: CS(C)=O
Product: O=C(Nc1nc2cc(Cl)ccc2o1)N1CCN(c2nc(-c3ccccc3)ns2)CC1
Yield: 24.3 %

Procedure:
A mixed solution of 2,2,2-trichloroethyl (5-chloro-1,3-benzoxazol-2-yl)carbamate (254 mg, 0.738 mmol), 1-(3-phenyl-1,2,4-thiadiazol-5-yl)piperazine (200 mg, 0.812 mmol) and diisopropylethylamine (0.129 ml, 0.738 mmol) in dimethyl sulfoxide (2.5 ml) was stirred at 70° C. for 3 hours. Water was poured to the reaction mixture, and the resulting solution was extracted with ethyl acetate. The extract was washed with water and dried over anhydrous magnesium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by high performance liquid chromatography (YMC HPLC Column eluted with 10% to 100% Liquid A; Liquid A: a 0.1% solution of trifluoroacetic acid in acetonitrile; Liquid B: an aqueous 0.1% trifluoroacetic acid solution) and recrystallized from a mixed solvent of hexane and ethyl acetate to give 79.2 mg (24.3%) of the desired product as a solid.
Reaction SMILES: C1(S([N:10]2[C:14]3=[N:15][CH:16]=[C:17]([F:19])[CH:18]=[C:13]3[CH:12]=[C:11]2[C:20]([C:27]2[CH:32]=[CH:31][C:30]([C:33]([OH:36])([CH3:35])[CH3:34])=[CH:29][CH:28]=2)=[CH:21][CH:22]2[CH2:26][CH2:25][CH2:24][CH2:23]2)(=O)=O)C=CC=CC=1.[OH-].[Na+].N>C(O)C.O1CCCC1>[CH:22]1([CH:21]=[C:20]([C:27]2[CH:32]=[CH:31][C:30]([C:33]([OH:36])([CH3:34])[CH3:35])=[CH:29][CH:28]=2)[C:11]2[NH:10][C:14]3=[N:15][CH:16]=[C:17]([F:19])[CH:18]=[C:13]3[CH:12]=2)[CH2:26][CH2:25][CH2:24][CH2:23]1
Reactant: CC(C)(O)c1ccc(C(=CC2CCCC2)c2cc3cc(F)cnc3n2S(=O)(=O)c2ccccc2)cc1
Agent: N
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Product: CC(C)(O)c1ccc(C(=CC2CCCC2)c2cc3cc(F)cnc3[nH]2)cc1
Temperature: 25 °C
Yield: 95.7 %

Procedure:
To a solution of 2-{4-[1-(1-benzenesulfonyl-5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-2-cyclopentyl-vinyl]-phenyl}-propan-2-ol (220 mg, 0.43 mmol) in ethanol (20 mL) and tetrahydrofuran (10 mL) was added an aqueous sodium hydroxide solution (10%, 3.0 mL) and an aqueous saturated ammonia solution (1.5 mL). The mixture was refluxed for 12 h, cooled to room temperature, extracted with ethyl acetate, dried over anhydrous sodium sulfate and then concentrated in vacuo to afford 2-{4-[2-cyclopentyl-1-(5-fluoro-1H-pyrrolo[2,3-b]pyridin-2-yl)-vinyl]-phenyl}-propan-2-ol (150 mg, 94%) which was used in the next step without purification: LC/MS m/e calcd for C23H25FN2O [M+H]+ 365.47, observed 365.3.
Reaction SMILES: BrC1C=CC=CC=1C(F)(F)F.CCCCCC.C([Li])CCC.Br[C:24]1[CH:25]=[C:26]2[C:31](=[CH:32][CH:33]=1)[CH:30]=[C:29]([C:34]([NH:36][CH3:37])=[O:35])[CH:28]=[CH:27]2.[C:38]([N:57]1[CH:61]=[C:60]([CH:62]=[O:63])[N:59]=[CH:58]1)([C:51]1[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=1)([C:45]1[CH:50]=[CH:49][CH:48]=[CH:47][CH:46]=1)[C:39]1[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=1.[Cl-].[NH4+]>C1COCC1>[OH:63][CH:62]([C:60]1[N:59]=[CH:58][N:57]([C:38]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][CH:40]=2)([C:45]2[CH:46]=[CH:47][CH:48]=[CH:49][CH:50]=2)[C:51]2[CH:56]=[CH:55][CH:54]=[CH:53][CH:52]=2)[CH:61]=1)[C:24]1[CH:25]=[C:26]2[C:31](=[CH:32][CH:33]=1)[CH:30]=[C:29]([C:34]([NH:36][CH3:37])=[O:35])[CH:28]=[CH:27]2
Reactant: CNC(=O)c1ccc2cc(Br)ccc2c1
Reactant: O=Cc1cn(C(c2ccccc2)(c2ccccc2)c2ccccc2)cn1
Agent: FC(F)(F)c1ccccc1Br
Agent: [Cl-]
Agent: [Li]CCCC
Solvent: CCCCCC
Solvent: C1CCOC1
Product: CNC(=O)c1ccc2cc(C(O)c3cn(C(c4ccccc4)(c4ccccc4)c4ccccc4)cn3)ccc2c1
Temperature: -70 °C
Reaction time: 0.5 h
Yield: 69.8 %

Procedure:
Under a nitrogen atmosphere, o-bromotrifluoromethylbenzene (1.35 kg, 6.00 mol) was added to tetrahydrofuran (7.9 L). The reaction mixture was cooled to −70° C., 1.6 mol/L n-butyllithium hexane solution (3.75 L, 6.00 mol) was added dropwise thereto, and the mixture was stirred at the same temperature for about 30 min. The reaction mixture was added dropwise at the same temperature to a solution prepared by adding 6-bromo-N-methyl-2-naphthamide (1.13 kg, 4.28 mol) to THF (62.2 L) at −70° C. under a nitrogen atmosphere, and the mixture was stirred for 1.5 hr. To the reaction mixture were added dropwise successively 1.6 mol/L n-butyllithium hexane solution (2.67 L, 4.27 mol) and a solution of 1-trityl-4-formyl-1H-imidazole (1.21 kg, 3.58 mol) in THF (7.9 L) at the same temperature, and the mixture was stirred for 2 hr. The reaction mixture was allowed to warm to −10° C., and 20 w/v % aqueous ammonium chloride solution (17.0 L) was added dropwise thereto at −10 to 0° C. The separated organic layer was concentrated under reduced pressure. To the residue was added ethyl acetate (11.3 L), and the mixture was stirred at room temperature. The crystals were collected by filtration, and washed with ethyl acetate (11.3 L). The obtained wet crystals were dried under reduced pressure to give 6-[hydroxy(1-trityl-1H-imidazol-4-yl)methyl]-N-methyl-2-naphthamide (1.31 kg, 2.50 mol). yield 58%.
Reaction SMILES: [I-].[K+].C[Si](Cl)(C)C.[CH2:8]([O:15][CH2:16][C:17]1[N:18]([CH2:34][C:35]2[CH:36]=[CH:37][C:38]([O:41]C)=[N:39][CH:40]=2)[C:19]([S:25][C:26]2[CH:31]=[C:30]([Cl:32])[CH:29]=[C:28]([Cl:33])[CH:27]=2)=[C:20]([CH:22]([CH3:24])[CH3:23])[N:21]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1.CO>C(#N)C>[CH2:8]([O:15][CH2:16][C:17]1[N:18]([CH2:34][C:35]2[CH:40]=[N:39][C:38](=[O:41])[CH2:37][CH:36]=2)[C:19]([S:25][C:26]2[CH:27]=[C:28]([Cl:33])[CH:29]=[C:30]([Cl:32])[CH:31]=2)=[C:20]([CH:22]([CH3:24])[CH3:23])[N:21]=1)[C:9]1[CH:14]=[CH:13][CH:12]=[CH:11][CH:10]=1
Reactant: COc1ccc(Cn2c(COCc3ccccc3)nc(C(C)C)c2Sc2cc(Cl)cc(Cl)c2)cn1
Agent: C[Si](C)(C)Cl
Agent: [I-]
Agent: [K+]
Solvent: CO
Solvent: CC#N
Product: CC(C)c1nc(COCc2ccccc2)n(CC2=CCC(=O)N=C2)c1Sc1cc(Cl)cc(Cl)c1
Temperature: 60 °C
Reaction time: 0.17 h
Yield: 34.2 %

Procedure:
To a solution of 83 mg of potassium iodide in acetonitrile was added 64 μl of trimethylsilyl chloride under ice-cooling and stirring. The mixture was allowed to warm up, and after 10 minutes, 150 mg of 2-benzyloxymethyl-5-(3,5-dichlorophenylthio)-1-(2-methoxypyridin-5-ylmethyl)-4-isopropyl-1H-imidazole was added, and the mixture was stirred with heating at 60° C. After 1 hour, the solution was distilled off under reduced pressure, an aqueous sodium hydrogen carbonate solution was added, extracted with ethyl acetate, the extract was dried over sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel chromatography (ethyl acetate:methanol=10:1)to give 50 mg of 2-benzyloxymethyl-5-(3,5-dichlorophenylthio)-1-(5,6-dihydro-6-oxopyridin-3-ylmethyl)-4-isopropyl-1H-imidazole (115a)(yield 34%).
Reaction SMILES: [CH3:1][C:2]1[CH:7]=[C:6]([O:8][CH2:9][CH2:10][CH2:11][S:12]([CH3:15])(=[O:14])=[O:13])[CH:5]=[C:4]([CH3:16])[C:3]=1[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH2:23][O:24][C:25]2[CH:37]=[CH:36][C:28]3[C:29]([CH2:32][C:33]([OH:35])=[O:34])=[CH:30][O:31][C:27]=3[CH:26]=2)[CH:18]=1.C(O)C>C(N(CC)CC)C>[CH3:16][C:4]1[CH:5]=[C:6]([O:8][CH2:9][CH2:10][CH2:11][S:12]([CH3:15])(=[O:14])=[O:13])[CH:7]=[C:2]([CH3:1])[C:3]=1[C:17]1[CH:22]=[CH:21][CH:20]=[C:19]([CH2:23][O:24][C:25]2[CH:37]=[CH:36][C:28]3[C@H:29]([CH2:32][C:33]([OH:35])=[O:34])[CH2:30][O:31][C:27]=3[CH:26]=2)[CH:18]=1
Reactant: Cc1cc(OCCCS(C)(=O)=O)cc(C)c1-c1cccc(COc2ccc3c(CC(=O)O)coc3c2)c1
Solvent: CCO
Solvent: CCN(CC)CC
Product: Cc1cc(OCCCS(C)(=O)=O)cc(C)c1-c1cccc(COc2ccc3c(c2)OC[C@H]3CC(=O)O)c1
Temperature: 50 °C
Reaction time: 24 h
Yield: 99.8 %

Procedure:
Under an argon atmosphere, to [6-({2′,6′-dimethyl-4′-[3-(methylsulfonyl)propoxy]biphenyl-3-yl}methoxy)-1-benzofuran-3-yl]acetic acid (522 mg), dichloro[(+)-1,2-bis((2R,5R)-2,5-diisopropylphosphorano)benzene]ruthenium (II)-N,N-dimethylformamide complex (7.4 mg) in an autoclave container was added a solution of dehydrated ethanol (6 mL) containing triethylamine (0.139 mL), and the mixture was stirred at 50° C. for 24 hr under a hydrogen atmosphere (1 MPa). The reaction mixture was concentrated, 10% aqueous citric acid solution (25 mL) and ethyl acetate (25 mL) were added, and an extraction operation was performed. The aqueous layer was extracted with ethyl acetate (25 mL), and the combined organic layer was washed with water (25 mL), dried over sodium sulfate and concentrated. The crude product was washed with diisopropyl ether. After filtration, the obtained solid was dried at 50° C. under reduced pressure to give the title compound (523 mg) as white crystals. 80.0% ee.
Reaction SMILES: [CH2:1]([N:8]1[C:12]([CH:13]=O)=[C:11]([Cl:15])[N:10]=[C:9]1[C:16]1[CH:21]=[CH:20][C:19]([N:22]([CH3:24])[CH3:23])=[CH:18][CH:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.Cl.[NH2:26]O.C(OC(=O)C)(=O)C>N1C=CC=CC=1>[CH2:1]([N:8]1[C:12]([C:13]#[N:26])=[C:11]([Cl:15])[N:10]=[C:9]1[C:16]1[CH:21]=[CH:20][C:19]([N:22]([CH3:24])[CH3:23])=[CH:18][CH:17]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NO
Reactant: CN(C)c1ccc(-c2nc(Cl)c(C=O)n2Cc2ccccc2)cc1
Agent: Cl
Solvent: CC(=O)OC(C)=O
Solvent: c1ccncc1
Product: CN(C)c1ccc(-c2nc(Cl)c(C#N)n2Cc2ccccc2)cc1
Temperature: 100 °C
Reaction time: 3 h
Yield: 62.3 %

Procedure:
In 30 ml of pyridine were dissolved 3.4 g of 1-benzyl-4-chloro-2-(4-dimethylaminophenyl)-5-formylimidazole and 1.39 g of hydroxylamine hydrochloride, and 6 ml of acetic anhydride was added dropwise to the solution. After the addition was completed, the reaction solution was stirred at 100° C. for 3 hours, and evaporated to dryness under reduced pressure. The residue was dissolved in 100 ml of chloroform, washed with two 300 ml portions of water, and evaporated to dryness under reduced pressure. The residue was recrystallized twice from 30 ml of ethanol, yielding 2.1 g of 1-benzyl-4-chloro-2-(4-dimethylaminophenyl)-5-cyanoimidazole as slightly brown needles, m.p. 125°-127° C.