Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH:1]([NH:4][C:5]([C:7]1[C:15]2[C:11](=[CH:12][NH:13][N:14]=2)[CH:10]=[C:9]([CH3:16])[C:8]=1[NH:17][C:18]([C:20]1[N:21]([C:27]2[C:32]([Cl:33])=[CH:31][CH:30]=[CH:29][N:28]=2)[N:22]=[C:23]([O:25][CH3:26])[CH:24]=1)=[O:19])=[O:6])([CH3:3])[CH3:2].C(N(CC)CC)C.Cl[C:42]([S:44][CH2:45][CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH3:52])=[O:43]>ClCCl>[CH2:45]([S:44][C:42]([N:13]1[CH:12]=[C:11]2[C:15]([C:7]([C:5](=[O:6])[NH:4][CH:1]([CH3:3])[CH3:2])=[C:8]([NH:17][C:18]([C:20]3[N:21]([C:27]4[C:32]([Cl:33])=[CH:31][CH:30]=[CH:29][N:28]=4)[N:22]=[C:23]([O:25][CH3:26])[CH:24]=3)=[O:19])[C:9]([CH3:16])=[CH:10]2)=[N:14]1)=[O:43])[CH2:46][CH2:47][CH2:48][CH2:49][CH2:50][CH2:51][CH3:52]
Reactant: CCCCCCCCSC(=O)Cl
Reactant: COc1cc(C(=O)Nc2c(C)cc3c[nH]nc3c2C(=O)NC(C)C)n(-c2ncccc2Cl)n1
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CCCCCCCCSC(=O)n1cc2cc(C)c(NC(=O)c3cc(OC)nn3-c3ncccc3Cl)c(C(=O)NC(C)C)c2n1
Temperature: 20 °C
Reaction time: 0.5 h

Procedure:
To a suspension of 6-{[2-(3-chloro-pyridin-2-yl)-5-methoxy-2H-pyrazole-3-carbonyl]-amino}-5-methyl-2H-indazole-7-carboxylic acid isopropylamide (0.300 g, 0.64 mmol) in dichloromethane (3.0 mL) was added triethylamine (90 μL, 0.65 mmol), then S-octyl chlorothioformate (0.133 g, 0.64 mmol). The resulting homogeneous reaction mixture was stirred for 0.5 h at 20° C. The reaction mixture was then concentrated in vacuo and the residue was purified by flash-chromatography (SiO2, CH2Cl2/ethyl acetate 9:1) affording the title compound as yellow crystals with a melting point of 98-102° C.
Reaction SMILES: [CH3:1][N:2]([CH3:13])[CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([NH2:12])=[CH:8][CH:7]=1.[CH3:14][C:15]1[CH:20]=[CH:19][CH:18]=[C:17]([CH3:21])[C:16]=1[C:22]1[C:31]2[N:30]=[CH:29][CH:28]=[N:27][C:26]=2[C:25]([C:32](O)=[O:33])=[CH:24][CH:23]=1>>[CH3:1][N:2]([CH3:13])[CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([NH:12][C:32]([C:25]2[C:26]3[N:27]=[CH:28][CH:29]=[N:30][C:31]=3[C:22]([C:16]3[C:17]([CH3:21])=[CH:18][CH:19]=[CH:20][C:15]=3[CH3:14])=[CH:23][CH:24]=2)=[O:33])=[CH:8][CH:7]=1
Reactant: CN(C)CCOc1ccc(N)cc1
Reactant: Cc1cccc(C)c1-c1ccc(C(=O)O)c2nccnc12
Product: Cc1cccc(C)c1-c1ccc(C(=O)Nc2ccc(OCCN(C)C)cc2)c2nccnc12

Procedure:
The title compound was prepared in analogy to the procedure described in Step 14.1 but using 4-(2-dimethylamino-ethoxy)-phenylamine (Step 5.1) and 8-(2,6-dimethyl-phenyl)-quinoxaline-5-carboxylic acid (Example 71). Title compound: ESI-MS: 441.1 [M+H]+; tR=3.52 min (System 3).
Reaction SMILES: Br[C:2]1[C:3]([C:11]2[CH:16]=[CH:15][C:14]([F:17])=[CH:13][CH:12]=2)=[N:4][N:5]2[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=12.[CH3:18][S:19][C:20]1[CH:25]=[CH:24][C:23](B(O)O)=[CH:22][CH:21]=1>>[F:17][C:14]1[CH:15]=[CH:16][C:11]([C:3]2[C:2]([C:23]3[CH:24]=[CH:25][C:20]([S:19][CH3:18])=[CH:21][CH:22]=3)=[C:6]3[CH:7]=[CH:8][CH:9]=[CH:10][N:5]3[N:4]=2)=[CH:12][CH:13]=1
Reactant: Fc1ccc(-c2nn3ccccc3c2Br)cc1
Reactant: CSc1ccc(B(O)O)cc1
Product: CSc1ccc(-c2c(-c3ccc(F)cc3)nn3ccccc23)cc1

Procedure:
By using 3-bromo-2-(4-fluorophenyl)pyrazolo[1,5-a]pyridine (4.0 g, 13.8 mmol) and 4-methylsulphanyl-phenylboronic acid (3.07 g, 1.83 mmol) the title compound was obtained as a white solid (2.29 g 50%) in the manner described in Example 2. MH+: 335; NMR: (CDCl3) δ 2.53 (3H, s) 6.80 (1H, t) 7.00 (2H, t) 7.15 (1H, t) 7.25 (2H, d) 7.30 (1H, d) 7.50 (2H, d) 7.60 (2H, m) 8.50 (1H, d).
Reaction SMILES: [F:1][C:2]1[N:7]=[C:6]([NH2:8])[CH:5]=[CH:4][CH:3]=1.[F:9][C:10]1[CH:11]=[C:12]([CH:18]=O)[CH:13]=[N:14][C:15]=1[O:16][CH3:17].C([SiH](CC)CC)C.FC(F)(F)C(O)=O>C(#N)C>[F:9][C:10]1[CH:11]=[C:12]([CH2:18][NH:8][C:6]2[CH:5]=[CH:4][CH:3]=[C:2]([F:1])[N:7]=2)[CH:13]=[N:14][C:15]=1[O:16][CH3:17]
Reactant: Nc1cccc(F)n1
Reactant: COc1ncc(C=O)cc1F
Agent: CC[SiH](CC)CC
Solvent: CC#N
Solvent: O=C(O)C(F)(F)F
Product: COc1ncc(CNc2cccc(F)n2)cc1F
Temperature: 80 °C
Reaction time: 8 h
Yield: 99 %

Procedure:
To 6-fluoro-pyridin-2-ylamine (43, 1.50 g, 13.4 mmol) in 52.9 mL of acetonitrile, 5-fluoro-6-methoxy-pyridine-3-carbaldehyde (57, 2.00 g, 12.9 mmol), triethylsilane (10.6 mL, 66.3 mmol), and trifluoroacetic acid (5.3 mL, 69.0 mmol) were added. The reaction was stirred at 80° C. overnight, then concentrated under vacuum, combined with water and extracted with ethyl acetate. The organic layer was dried over sodium sulfate, filtered and the filtrate concentrated under vacuum. The resulting material was purified by silica gel column chromatography, eluting with 15-100% ethyl acetate in hexane. Appropriate fractions were combined and concentrated under vacuum to provide the desired compound as white solid (58, 3.21 g).
Reaction SMILES: [F:1][C:2]1[CH:3]=[CH:4][C:5]([OH:11])=[C:6]([C:8](=[O:10])[CH3:9])[CH:7]=1.C(=O)([O-])[O-].[K+].[K+].CC(=O)CC.O.[Br:24][CH2:25][CH2:26]Br>>[Br:24][CH2:25][CH2:26][O:11][C:5]1[CH:4]=[CH:3][C:2]([F:1])=[CH:7][C:6]=1[C:8](=[O:10])[CH3:9]
Reactant: CC(=O)c1cc(F)ccc1O
Reactant: BrCCBr
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(C)=O
Solvent: O
Product: CC(=O)c1cc(F)ccc1OCCBr
Reaction time: 8 h
Yield: 21.9 %

Procedure:
Dissolved 1-(5-fluoro-2-hydroxyphenyl)ethanone (10.0 g, 64.9 mmol) in 18 mL 1,2-Dibromoethane and added Potassium carbonate (18.8 g, 136 mmol) and 100 mL 2-Butanone. Heated the reaction mixture to reflux and allowed to stir overnight under nitrogen. Reaction was complete by LCMS. Diluted reaction mixture with water and extracted the product with ethyl acetate. Concentrated in vacuo and purified by flash chromatography (0 to 30% ethyl acetate/heptanes) to give 3.71 g (21.9% yield) of 1-(2-(2-bromoethoxy)-5-fluorophenyl)ethanone.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[NH2:8].[Cl:9][CH2:10][CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:22]=[CH:21][C:18]([CH:19]=O)=[CH:17][CH:16]=1.CO>O.O.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[Cl:9][CH2:10][CH2:11][CH2:12][CH2:13][O:14][C:15]1[CH:16]=[CH:17][C:18]([C:19]2[NH:8][C:3]3[CH:4]=[CH:5][CH:6]=[CH:7][C:2]=3[N:1]=2)=[CH:21][CH:22]=1
Reactant: O=Cc1ccc(OCCCCCl)cc1
Reactant: Nc1ccccc1N
Agent: [Cu+2]
Agent: CC(=O)[O-]
Solvent: O
Solvent: CO
Product: ClCCCCOc1ccc(-c2nc3ccccc3[nH]2)cc1
Yield: 65.1 %

Procedure:
A mixture of copper (II) acetate monohydrate (7.76 g), 1,2-diaminobenzene (2.10 g), 4-(4-chlorobutoxy]benzaldehyde (Step A) (5.0 g) is slowly heated to reflux in water (10 mL) and methanol (100 mL) and stirred at reflux for 1 hour. The mixture is cooled and a brown precipitate filtered off. The precipitate is suspended in methanol (100 mL) and hydrogen sulfide bubbled through for 30 minutes followed by nitrogen. The mixture is heated to reflux, cooled and filtered. All the filtrates are combined and 0.880 ammonium hydroxide added until just basic. The filtrates are diluted with an equal volume of water and the resulting pale-grey precipitate collected. The precipitate is recrystallized from methanol/water to give 3.8 g of the title compound.
Reaction SMILES: [OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:12]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[OH:19])[N:10]([C:20]2[CH:28]=[CH:27][C:23]([C:24]([OH:26])=O)=[CH:22][CH:21]=2)[N:9]=1.C(N(CC)CC)C.[CH3:36][N:37]1[CH2:42][CH2:41][NH:40][CH2:39][CH2:38]1>O1CCCC1>[OH:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[N:12]=[C:11]([C:13]2[CH:18]=[CH:17][CH:16]=[CH:15][C:14]=2[OH:19])[N:10]([C:20]2[CH:28]=[CH:27][C:23]([C:24]([N:40]3[CH2:41][CH2:42][N:37]([CH3:36])[CH2:38][CH2:39]3)=[O:26])=[CH:22][CH:21]=2)[N:9]=1
Reactant: CN1CCNCC1
Reactant: O=C(O)c1ccc(-n2nc(-c3ccccc3O)nc2-c2ccccc2O)cc1
Solvent: CCN(CC)CC
Solvent: C1CCOC1
Product: CN1CCN(C(=O)c2ccc(-n3nc(-c4ccccc4O)nc3-c3ccccc3O)cc2)CC1
Temperature: 25 °C
Reaction time: 48 h

Procedure:
3 g of 4-[3,5-bis(2-hydroxyphenyl)-[1,2,4]triazol-1-yl]-benzoic acid (Example 5) and 1.25 ml of 1-chloro-N,N-2-trimethyl-1-propen-1-amine are stirred for 2 h in 50 ml of tetrahydrofuran. 2.2 ml of triethylamine and 1 ml of N-methylpiperazine are added and the mixture is stirred at room temperature for 48 h. It is poured onto water and extracted with ethyl acetate. The combined organic phases are dried over sodium sulfate and concentrated on a rotary evaporator. The residue is crystallized from isopropanol. After drying, {4-[3,5-bis(2-hydroxy-phenyl)-[1,2,4]triazol-1-yl]-phenyl}-(4-methylpiperazin-1-yl)methanone remains as colorless crystals of m.p. 226-229° C.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:9]([S:12]([N:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)(=[O:14])=[O:13])=[CH:8][C:4]=1[C:5]([OH:7])=O.[CH3:21][O:22][C:23]1[C:24]([NH2:29])=[N:25][CH:26]=[CH:27][CH:28]=1>>[CH3:1][O:2][C:3]1[CH:11]=[CH:10][C:9]([S:12]([N:15]2[CH2:20][CH2:19][CH2:18][CH2:17][CH2:16]2)(=[O:14])=[O:13])=[CH:8][C:4]=1[C:5]([NH:29][C:24]1[C:23]([O:22][CH3:21])=[CH:28][CH:27]=[CH:26][N:25]=1)=[O:7]
Reactant: COc1cccnc1N
Reactant: COc1ccc(S(=O)(=O)N2CCCCC2)cc1C(=O)O
Product: COc1ccc(S(=O)(=O)N2CCCCC2)cc1C(=O)Nc1ncccc1OC

Procedure:
The entitled compound was produced according to the method of Example 92 but using 2-methoxy-5-(piperidin-1-ylsulfonyl)benzoic acid and 3-methoxypyridine-2-amine as the starting materials.