Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].Cl.[N:8]1([C:14]2[C:18]3[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=3[S:16][N:15]=2)[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]1.S(C1C=CC(C)=CC=1)(O[CH2:27][CH2:28][C:29]1[CH:34]=[CH:33][C:32]([N+:35]([O-:37])=[O:36])=[CH:31][CH:30]=1)(=O)=O>CC(C)=O.C1OCCOCCOCCOCCOCCOC1>[N+:35]([C:32]1[CH:33]=[CH:34][C:29]([CH2:28][CH2:27][N:11]2[CH2:12][CH2:13][N:8]([C:14]3[C:18]4[CH:19]=[CH:20][CH:21]=[CH:22][C:17]=4[S:16][N:15]=3)[CH2:9][CH2:10]2)=[CH:30][CH:31]=1)([O-:37])=[O:36]
Reactant: c1ccc2c(N3CCNCC3)nsc2c1
Reactant: Cc1ccc(S(=O)(=O)OCCc2ccc([N+](=O)[O-])cc2)cc1
Agent: C1COCCOCCOCCOCCOCCO1
Agent: Cl
Agent: O=C([O-])[O-]
Solvent: CC(C)=O
Product: O=[N+]([O-])c1ccc(CCN2CCN(c3nsc4ccccc34)CC2)cc1
Yield: 86.7 %

Procedure:
Excess dried, −325 mesh potassium carbonate (20 g) was diluted in 500 mL acetone and 3-piperazin-1-yl-benzoisothiazole hydrochloride (13.05 g, 51.2 mmol) was added. The mixture was stirred for 15 min before 4-nitrophenethyl tosylate (14.93 g, 46.5 mmol) and catalytic 18-crown-6 (0.5 g, 1.9 mmol) was added. The mixture was stirred at reflux for 42 h. After cooling, the salts were filtered off and washed with acetone and the filtrate was concentrated. The residue was taken up in methylene chloride and washed with water. The organic layer was dried over sodium sulfate, and concentrated. The residue was triturated with ethyl acetate and the collected solid was washed with ethyl ether and dried in vacuo to afford 14.86 g of a bright yellow solid. Yield 84%; mp 99° C.; MS (APCI): 369 [M+H]+.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]2[C:9]3[C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:15][NH:14][C:10]=3[N:11]=[CH:12][N:13]=2)[CH:5]=[CH:6][CH:7]=1.CCN(C(C)C)C(C)C.[C:31](Cl)(=[O:35])[C:32]([CH3:34])=[CH2:33]>C1COCC1>[CH3:34][C:32](=[CH2:33])[C:31]([NH:1][C:2]1[CH:3]=[C:4]([C:8]2[C:9]3[C:16]([C:17]([O:19][CH2:20][CH3:21])=[O:18])=[CH:15][NH:14][C:10]=3[N:11]=[CH:12][N:13]=2)[CH:5]=[CH:6][CH:7]=1)=[O:35]
Reactant: CCOC(=O)c1c[nH]c2ncnc(-c3cccc(N)c3)c12
Reactant: C=C(C)C(=O)Cl
Solvent: CCN(C(C)C)C(C)C
Solvent: C1CCOC1
Product: C=C(C)C(=O)Nc1cccc(-c2ncnc3[nH]cc(C(=O)OCC)c23)c1
Reaction time: 1 h

Procedure:
To a solution of ethyl 4-(3-aminophenyl)-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate (50 mg, 0.18 mmol) and DIPEA (93 μL, 0.53 mmol) in THF (1.8 mL) at room temperature was added methacryloyl chloride (27.8 mg, 0.266 mmol) and the solution stirred for 1 hour. The reaction was quenched with ethanol (0.1 mL). The desired product was purified by reverse phase HPLC using an acetonitrile gradient in water with 0.1% TFA modifier. The combined fractions with the desired product were concentrated until only the water layer remained. The water layer was neutralized with 2M aqueous potassium bicarbonate and the mixture was extracted with ethyl acetate (×5). The combined organic fractions were dried over sodium sulfate, filtered and concentrated under reduced pressure to give ethyl 4-{3-[(2-methylacryloyl)amino]phenyl}-7H-pyrrolo[2,3-d]pyrimidine-5-carboxylate. LRMS (ESI) calc'd for C19H19N4O3 [M+H]+: 351, found 351. 1H NMR (600 MHz, DMSO-D6) δ 13.0 (s, 1H), 9.91 (s, 1H), 8.91 (s, 1H), 8.30 (s, 1H), 8.05 (s, 1H), 7.84 (d, 1H, J=7.04 Hz), 7.40 (t, 1H, J=7.63 Hz), 7.32 (d, 1H, J=7.04 Hz), 5.82 (s, 1H), 5.53 (s, 1H), 3.86 (q, 2H, J=7.04 Hz), 1.95 (s, 3H), 0.85 (t, 3H, J=7.04 Hz).
Reaction SMILES: [CH3:1][Si:2]([C:5]#[CH:6])([CH3:4])[CH3:3].[C:7]1([S:13]([NH:16][C:17]2[C:22](I)=[CH:21][C:20]([S:24][CH3:25])=[CH:19][N:18]=2)(=[O:15])=[O:14])[CH:12]=[CH:11][CH:10]=[CH:9][CH:8]=1.C(N(CC)CC)C.O1CCOCC1>Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.C(OCC)(=O)C.O>[C:7]1([S:13]([N:16]2[C:17]3=[N:18][CH:19]=[C:20]([S:24][CH3:25])[CH:21]=[C:22]3[CH:6]=[C:5]2[Si:2]([CH3:4])([CH3:3])[CH3:1])(=[O:14])=[O:15])[CH:8]=[CH:9][CH:10]=[CH:11][CH:12]=1
Reactant: C#C[Si](C)(C)C
Reactant: CSc1cnc(NS(=O)(=O)c2ccccc2)c(I)c1
Agent: Cl[Pd](Cl)([P](c1ccccc1)(c1ccccc1)c1ccccc1)[P](c1ccccc1)(c1ccccc1)c1ccccc1
Solvent: C1COCCO1
Solvent: CCOC(C)=O
Solvent: O
Product: CSc1cnc2c(c1)cc([Si](C)(C)C)n2S(=O)(=O)c1ccccc1
Temperature: 70 °C
Reaction time: 16 h
Yield: 80.3 %

Procedure:
A mixture of trimethylsilylacetylene (0.41 g), 2-benzenesulfonylamino-3-iodo-5-methylthiopyridine (0.82 g), triethylamine (0.42 g), cuprous iodide (30 mg), dichlorobis(triphenylphosphine)palladium (75 mg) and dioxane (2 ml) was stirred at 70° C. for 16 hours under nitrogen atmosphere. To the reaction solution were then added water and ethyl acetate. The insolubles were filtered off. To the filtrate was added a saturated aqueous sodium hydrogencarbonate solution, and the mixture was extracted with ethyl acetate, dried over anhydrous sodium sulfate, filtered and concentrated. The resulting residue was subjected to silica gel column chromatography (hexane:ethyl acetate=10:1) to obtain 0.61 g of the desired product.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([C@H:11]1[CH2:15][NH:14][C@H:13]([C:16]([NH:18][C:19]2([C:22]#[N:23])[CH2:21][CH2:20]2)=[O:17])[CH2:12]1)(=[O:10])=[O:9].[CH3:24][C:25]1([CH3:38])[CH2:30][CH2:29][CH:28]([N:31]2[CH2:34][CH2:33][CH:32]2[C:35]([O-])=[O:36])[CH2:27][CH2:26]1.[Li+]>>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[S:8]([C@H:11]1[CH2:15][N:14]([C:35]([CH:32]2[CH2:33][CH2:34][N:31]2[CH:28]2[CH2:29][CH2:30][C:25]([CH3:38])([CH3:24])[CH2:26][CH2:27]2)=[O:36])[C@H:13]([C:16]([NH:18][C:19]2([C:22]#[N:23])[CH2:21][CH2:20]2)=[O:17])[CH2:12]1)(=[O:10])=[O:9]
Reactant: CC1(C)CCC(N2CCC2C(=O)[O-])CC1
Reactant: N#CC1(NC(=O)[C@@H]2C[C@@H](S(=O)(=O)c3ccccc3Cl)CN2)CC1
Agent: [Li+]
Product: CC1(C)CCC(N2CCC2C(=O)N2C[C@H](S(=O)(=O)c3ccccc3Cl)C[C@H]2C(=O)NC2(C#N)CC2)CC1

Procedure:
The reaction of (2S,4R)-4-(2-chlorophenylsulfonyl)-N-(1-cyanocyclopropyl)pyrrolidine-2-carboxamide 7H and lithium 1-(4,4-dimethylcyclohexyl)azetidine-2-carboxylate 20C carried out according to the general procedure L yielded (2S,4R)-4-(2-chlorophenylsulfonyl)-N-(1-cyanocyclopropyl)-1-(1-(4,4-dimethylcyclohexyl)azetidine-2-carbonyl)pyrrolidine-2-carboxamide 1:1 epimers as an off-white solid (74%). MS ISP (m/e): 547.1 (100) [(M+H)]]+.
Reaction SMILES: [F:1][C:2]([F:33])([F:32])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19]1[CH:31]=[CH:30][C:22]([CH:23]=[CH:24][C:25]([O:27]CC)=[O:26])=[CH:21][CH:20]=1.[OH-].[Na+].O.C(O)C>C(O)(=O)C>[F:1][C:2]([F:32])([F:33])[CH2:3][CH2:4][CH2:5][CH2:6][CH2:7][CH2:8][CH2:9][CH2:10][CH2:11][CH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][NH:18][C:19]1[CH:31]=[CH:30][C:22]([CH:23]=[CH:24][C:25]([OH:27])=[O:26])=[CH:21][CH:20]=1
Reactant: CCOC(=O)C=Cc1ccc(NCCCCCCCCCCCCCCCC(F)(F)F)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Solvent: CC(=O)O
Product: O=C(O)C=Cc1ccc(NCCCCCCCCCCCCCCCC(F)(F)F)cc1

Procedure:
A mixture of ethyl 4-aminocinnamate, one equivalent of 15-(trifluoromethyl)pentadecyl bromide and one equivalent of anhydrous potassium carbonate in hexamethylphosphoramide is heated for 20 hours at 60° C. The mixture is then cooled, diluted with water and extracted with ether. The combined ether extracts are dried, filtered and evaporated to provide ethyl 4-[15-(trifluoromethyl)pentadecylamino]cinnamate. The ester is hydrolyzed with sodium hydroxide in a 1:9 water:ethanol solution at steam bath temperatures for 10 hours. The hot solution is then acidified with acetic acid, cooled and filtered and the solid is washed with water. Recrystallization from chloroform yields the product as a white solid.
Reaction SMILES: [C:1]([C:4]1[S:8][C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[CH:5]=1)(=O)[CH3:2].S1C=CC2C=CC=CC1=2.C([Li])CCC.C[N:28]([C:31](=[O:33])[CH3:32])[O:29]C>C1COCC1>[OH:29][N:28]([CH:1]([C:4]1[S:8][C:7]2[CH:9]=[CH:10][CH:11]=[CH:12][C:6]=2[CH:5]=1)[CH3:2])[C:31](=[O:33])[CH3:32]
Reactant: CC(=O)c1cc2ccccc2s1
Reactant: CON(C)C(C)=O
Agent: [Li]CCCC
Agent: c1ccc2sccc2c1
Solvent: C1CCOC1
Product: CC(=O)N(O)C(C)c1cc2ccccc2s1
Temperature: -78 °C
Reaction time: 0.25 h

Procedure:
2-Acetyl benzo[b]thiophene. Method a. Using the method described in Scheme 1, benzo[b]thiophene (10 g, 75 mmole) was dissolved in THF (50 mL) and cooled to -78° C. Butyl lithium (28 mL, 2.7 M in hexanes) was added. The mixture was stirred for 15 minutes and N,O-dimethyl acetohydroxamic acid was added. Following an additional 30 minutes of stirring, the reaction was quenched at -78° C. with ethanol and 2N HC1 solution and extracted into ether. The solvent was removed in vacuo and the residue chromatographed on silica gel eluting with 20% ether in pentane to yield 6.9 g of the desired product as a white solid.
Reaction SMILES: [CH3:1][C:2]1[CH:15]=[C:14]2[C:5]([O:6][C:7]3[CH:8]=[CH:9][C:10]([C:16]([OH:18])=[O:17])=[CH:11][C:12]=3[CH2:13]2)=[CH:4][CH:3]=1.[CH3:19]O.S(=O)(=O)(O)O>O>[CH3:1][C:2]1[CH:15]=[C:14]2[C:5]([O:6][C:7]3[CH:8]=[CH:9][C:10]([C:16]([O:18][CH3:19])=[O:17])=[CH:11][C:12]=3[CH2:13]2)=[CH:4][CH:3]=1
Reactant: Cc1ccc2c(c1)Cc1cc(C(=O)O)ccc1O2
Reactant: CO
Agent: O=S(=O)(O)O
Solvent: O
Product: COC(=O)c1ccc2c(c1)Cc1cc(C)ccc1O2
Temperature: 40 °C

Procedure:
Twenty-six grams of 7-methylxanthene-2-carboxylic acid is added to 400 ml. of absolute methanol. To the resultant solution are added 18 ml. of concentrated sulfuric acid and the mixture is then heated at reflux for about two hours. The mixture is then cooled to 40°C and sufficient water is added to bring the total volume to 1400 ml. The resultant mixture is then filtered to give methyl 7-methylxanthene-2-carboxylate.
Reaction SMILES: [OH-].[Na+].[Cl:3][C:4]1[CH:5]=[C:6]([N+:10](=[N:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)[O-])[CH:7]=[CH:8][CH:9]=1>[Ni].CO.O>[Cl:3][C:4]1[CH:5]=[C:6]([NH:10][NH:12][C:13]2[CH:18]=[CH:17][CH:16]=[C:15]([Cl:19])[CH:14]=2)[CH:7]=[CH:8][CH:9]=1
Reactant: [O-][N+](=Nc1cccc(Cl)c1)c1cccc(Cl)c1
Agent: [Ni]
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: Clc1cccc(NNc2cccc(Cl)c2)c1
Temperature: 10 °C
Yield: 89 %

Procedure:
1.2 g of sodium hydroxide and 0.25 g of Raney nickel are added to a suspension of 53.4 g of 3,3'-dichloroazoxybenzene in 60 ml of methanol and 15 ml of water and the hydrogenation reaction is carried out under a hydrogen pressure of 10 bars. After 90 minutes the mixture is cooled to 10° C. and the product is isolated by filtration. 3,3'-Dichlorohydrazobenzene is obtained in a yield of 89% of theory.
Reaction SMILES: [O:1]=[C:2]1[C:10]2[CH:9]=[C:8]3[CH:11]=[CH:12][CH:13]=[CH:14][C:7]3=[CH:6][C:5]=2[C:4](=[O:15])[N:3]1[CH2:16][CH2:17][C@@H:18]([NH:22][C@H:23]([C:28]([NH:30][CH2:31]C1C=CC=C(C(F)(F)F)C=1)=[O:29])[CH2:24][CH:25]([CH3:27])[CH3:26])[C:19]([OH:21])=[O:20].CC(C([C@H](N[C@@H](CC(C)C)C(NC[C:72]1[CH:80]=[CH:79][C:75]([C:76]([OH:78])=[O:77])=[CH:74][CH:73]=1)=O)CCN1C(=O)C2C=C3C=CC=CC3=CC=2C1=O)=O)(C)C>>[C:19]([C@H:18]([NH:22][C@@H:23]([CH2:24][CH:25]([CH3:27])[CH3:26])[C:28]([NH:30][CH2:31][C:72]1[CH:80]=[CH:79][C:75]([C:76]([OH:78])=[O:77])=[CH:74][CH:73]=1)=[O:29])[CH2:17][CH2:16][N:3]1[C:2](=[O:1])[C:10]2[CH:9]=[C:8]3[CH:11]=[CH:12][CH:13]=[CH:14][C:7]3=[CH:6][C:5]=2[C:4]1=[O:15])([OH:21])=[O:20]
Reactant: CC(C)C[C@H](N[C@H](CCN1C(=O)c2cc3ccccc3cc2C1=O)C(=O)O)C(=O)NCc1cccc(C(F)(F)F)c1
Reactant: CC(C)C[C@H](N[C@H](CCN1C(=O)c2cc3ccccc3cc2C1=O)C(=O)C(C)(C)C)C(=O)NCc1ccc(C(=O)O)cc1
Product: CC(C)C[C@H](N[C@H](CCN1C(=O)c2cc3ccccc3cc2C1=O)C(=O)O)C(=O)NCc1ccc(C(=O)O)cc1

Procedure:
Prepared as described for Example 1, Part (b) by hydrolysis of the product of Part (a) above to give the title compound as a solid; 20 mg.
Reaction SMILES: [OH:1][C:2]1[CH:3]=[C:4]([CH2:13][C:14]([O:16][CH3:17])=[O:15])[CH:5]=[C:6]([O:11][CH3:12])[C:7]=1[N+:8]([O-])=O>C(O)C.[Pd]>[NH2:8][C:7]1[C:6]([O:11][CH3:12])=[CH:5][C:4]([CH2:13][C:14]([O:16][CH3:17])=[O:15])=[CH:3][C:2]=1[OH:1]
Reactant: COC(=O)Cc1cc(O)c([N+](=O)[O-])c(OC)c1
Agent: [Pd]
Solvent: CCO
Product: COC(=O)Cc1cc(O)c(N)c(OC)c1
Yield: 100.8 %

Procedure:
A solution of methyl 3-hydroxy-5-methoxy-4-nitrophenylacetate (0.34 g, Reference Example 11) in ethanol (25 mL) was treated with palladium on charcoal (approximately 0.035 g, 10%) and stirred under a hydrogen atmosphere. After 2 hours the mixture was filtered through a pad of celite and the filtrate was evaporated to give the title compound (0.3 g ) as a brown oil.