Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: Cl[C:2]1[N:3]=[C:4]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([O:30][CH3:31])=[CH:26][CH:25]=2)[C:5]2[C:10]([C:11]#[N:12])=[CH:9][N:8](S(C3C=CC(C)=CC=3)(=O)=O)[C:6]=2[N:7]=1.[NH2:32][C:33]1[CH:34]=[C:35]2[C:40](=[CH:41][CH:42]=1)[NH:39][C:38](=[O:43])[CH2:37][CH2:36]2.C[Si](Cl)(C)C>C(O)CCC>[CH3:31][O:30][C:27]1[CH:26]=[CH:25][C:24]([NH:23][C:4]2[C:5]3[C:10]([C:11]#[N:12])=[CH:9][NH:8][C:6]=3[N:7]=[C:2]([NH:32][C:33]3[CH:34]=[C:35]4[C:40](=[CH:41][CH:42]=3)[NH:39][C:38](=[O:43])[CH2:37][CH2:36]4)[N:3]=2)=[CH:29][CH:28]=1
Reactant: COc1ccc(Nc2nc(Cl)nc3c2c(C#N)cn3S(=O)(=O)c2ccc(C)cc2)cc1
Reactant: Nc1ccc2c(c1)CCC(=O)N2
Agent: C[Si](C)(C)Cl
Solvent: CCCCO
Product: COc1ccc(Nc2nc(Nc3ccc4c(c3)CCC(=O)N4)nc3[nH]cc(C#N)c23)cc1
Temperature: 135 °C
Reaction time: 20 h
Yield: 7.8 %

Procedure:
A mixture of 2-chloro-4-(4-methoxyphenylamino)-7-tosyl-7H-pyrrolo[2,3-d]pyrimidine-5-carbonitrile (68 mg, 0.15 mmol), 6-amino-3,4-dihydroquinolin-2(1H)-one (40 mg, 0.24 mmol) and trimethylsilyl chloride (0.100 mL, 0.790 mmol) in nBuOH (2 mL) was stirred at 135° C. for 20 h. More 6-amino-3,4-dihydroquinolin-2(1H)-one (24 mg, 0.15 mmol) and trimethylsilyl chloride (0.200 mL, 1.58 mmol) were added. It was stirred at 135° C. for another 20 h. nBuOH was removed in vacuo. The residue was purified by HPLC to give the titled compound (5 mg). MS 426.4 (M+H); UV 203.5, 290.3 nm.
Reaction SMILES: [C:1]([C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[NH:6][CH:5]=1)(=[O:3])[CH3:2].[H-].[Na+].[CH3:15]I>C1COCC1>[C:1]([C:4]1[C:12]2[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=2)[N:6]([CH3:15])[CH:5]=1)(=[O:3])[CH3:2]
Reactant: CI
Reactant: CC(=O)c1c[nH]c2ccccc12
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(=O)c1cn(C)c2ccccc12
Reaction time: 0.5 h

Procedure:
3-Acetyl-1H-indole (4.00 g, 0.025 mol) was dissolved in dry THF (100 ml), and treated with 80% sodium hydride (0.794 g, 0.0263 mol) with stirring under Ar. After 0.5 h, methyl iodide (2.36 ml, 0.038 mol) was added. After 20 h, the reaction mixture was evaporated under reduced pressure and the residue partitioned between ethyl acetate and water. The organic layer was then dried (Na2SO4), and evaporated under reduced pressure to give the title compound as a pale brown oil which crystallised on standing (4.20 g, 97%).
Reaction SMILES: [CH2:1]([O:5][C:6]1[N:14]=[C:13]2[C:9]([N:10]=[C:11]([O:22]C)[N:12]2[CH2:15][CH:16]2[CH2:21][CH2:20][CH2:19][NH:18][CH2:17]2)=[C:8]([NH2:24])[N:7]=1)[CH2:2][CH2:3][CH3:4].I[CH2:26][CH:27]([CH3:29])[CH3:28]>>[NH2:24][C:8]1[N:7]=[C:6]([O:5][CH2:1][CH2:2][CH2:3][CH3:4])[N:14]=[C:13]2[C:9]=1[NH:10][C:11](=[O:22])[N:12]2[CH2:15][CH:16]1[CH2:21][CH2:20][CH2:19][N:18]([CH2:26][CH:27]([CH3:29])[CH3:28])[CH2:17]1
Reactant: CC(C)CI
Reactant: CCCCOc1nc(N)c2nc(OC)n(CC3CCCNC3)c2n1
Product: CCCCOc1nc(N)c2[nH]c(=O)n(CC3CCCN(CC(C)C)C3)c2n1

Procedure:
Prepared similarly to Example 24 from 2-(butyloxy)-8-(methyloxy)-9-(3-piperidinylmethyl)-9H-purin-6-amine and 1-iodo-2-methylpropane.
Reaction SMILES: Br[C:2]1[CH:7]=[CH:6][N:5]=[CH:4][C:3]=1[CH:8]=[O:9].P([O-])([O-])([O-])=O.[K+].[K+].[K+].O1[CH2:23][CH2:22][O:21][CH2:20]C1>C(OCC)(=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[OH:9][CH2:8][C:3]1[CH:4]=[N:5][CH:6]=[CH:7][C:2]=1[C:7]1[CH:2]=[C:3]([CH:4]=[CH:23][C:22]=1[O:21][CH3:20])[CH:8]=[O:9]
Reactant: C1COCCO1
Reactant: O=Cc1cnccc1Br
Agent: [Pd]
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: CCOC(C)=O
Product: COc1ccc(C=O)cc1-c1ccncc1CO
Reaction time: 8 h

Procedure:
A flask was with charged 4-bromo-pyridine-3-carbaldehyde (376 mg, 2 mmol), 3-formal-6-methoxyphenelboronic acid (432 mg, 2.4 mmol), tetrakis(triphenylphosphine) palladium(0) (116 mg, 0.1 mmol), potassium phosphate (638 mg, 3 mmol) and 1,4-dioxane (20 mL). The reaction mixture was kept at 80° C. overnight, then diluted with ethyl acetate and washed with water then brine. The organic layer was dried over sodium sulfate, concentrated, and the residue purified by flash chromatography to yield 3-(3-hydroxymethyl-pyridin-4-yl)-4-methoxy-benzaldehyde as a yellow oil.
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[S:9][CH:10]=[C:11]([C:13]3[N:21]=[CH:20][CH:19]=[CH:18][C:14]=3[C:15]([OH:17])=O)[N:12]=2)=[CH:4][CH:3]=1.[NH2:22][CH:23]([CH2:29][C:30]1[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1)[CH:24]([OH:28])[C:25]([NH2:27])=[O:26]>>[NH2:27][C:25](=[O:26])[CH:24]([OH:28])[CH:23]([NH:22][C:15](=[O:17])[C:14]1[CH:18]=[CH:19][CH:20]=[N:21][C:13]=1[C:11]1[N:12]=[C:8]([C:5]2[CH:4]=[CH:3][C:2]([F:1])=[CH:7][CH:6]=2)[S:9][CH:10]=1)[CH2:29][C:30]1[CH:31]=[CH:32][CH:33]=[CH:34][CH:35]=1
Reactant: O=C(O)c1cccnc1-c1csc(-c2ccc(F)cc2)n1
Reactant: NC(=O)C(O)C(N)Cc1ccccc1
Product: NC(=O)C(O)C(Cc1ccccc1)NC(=O)c1cccnc1-c1csc(-c2ccc(F)cc2)n1
Yield: 93.7 %

Procedure:
Coupling of 2-(2-(4-fluorophenyl)thiazol-4-yl)nicotinic acid (350 mg, 1.165 mmol) and 3-amino-2-hydroxy-4-phenylbutanamide (270 mg, 1.39 mmol) in an analogous manner as described for example 1.2 afforded 520 mg of the title compound as white amorphous solid; ESI-MS [M+H+]: 477.1.
Reaction SMILES: Cl.[CH3:2][CH:3]([CH2:18][CH3:19])[C:4](=O)[C:5]([NH:7][CH2:8][C:9]([C:11]1[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=1)=O)=[O:6].C(#[N:22])C>>[CH3:2][CH:3]([C:4]1[C:5](=[O:6])[NH:7][CH:8]=[C:9]([C:11]2[CH:12]=[N:13][CH:14]=[CH:15][CH:16]=2)[N:22]=1)[CH2:18][CH3:19]
Reactant: CCC(C)C(=O)C(=O)NCC(=O)c1cccnc1
Reactant: CC#N
Agent: Cl
Product: CCC(C)c1nc(-c2cccnc2)c[nH]c1=O

Procedure:
In a manner analogous to Example 1, by condensing 3-(2-amino-1,1-diethoxyethyl)pyridine with 3-methyl-2-oxopentanoic acid there is obtained rac-N-[2,2-diethoxy-2-(3-pyridyl)ethyl]-3-methyl-2-oxovaleramide as an amorphous, colorless solid. Subsequent acidic hydrolysis to rac-3-methyl-2-oxo-N-[(3-pyridylcarbonyl)methyl]valeramide hydrochloride (beige, crystalline solid, melting point 158°-159°) and ring closure gives rac-3-(1-methylpropyl)-5-(3-pyridyl)-2(1H)-pyrazinone as a yellow solid, melting point 146°-148° (from acetonitrile). The conversion into rac-2-chloro-3-(1-methylpropyl)-5-(3-pyridyl)pyrazine is also effected analogously to Example 1. Hydrazinolysis to rac-2-hydrazino-3-(1-methylpropyl)-5-(3-pyridyl)pyrazine in the form of beige crystals, melting point 166°-167° (from ethanol/water) and subsequent condensation with diethyl malonate gives ethyl rac-8-(1-methylpropyl)-6-(3-pyridyl)-s-triazolo[4,3-a]pyrazine-3-acetate, MS: 335 (M)+, which is converted by saponification into the above acid, MS: 267 (M-CO 2)+.
Reaction SMILES: C(N(CC)CC)C.Cl.[CH3:9][O:10][C:11]1[CH:17]=[C:16]([O:18][CH3:19])[CH:15]=[C:14]([O:20][CH3:21])[C:12]=1[NH2:13].[CH2:22]([C:34]1[CH:38]=[N:37][N:36]([CH:39]([C:43]2[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=2)[C:40](O)=[O:41])[N:35]=1)[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33].C1(N=C=NC2CCCCC2)CCCCC1>C1COCC1.ClCCl>[CH2:22]([C:34]1[CH:38]=[N:37][N:36]([CH:39]([C:43]2[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=2)[C:40]([NH:13][C:12]2[C:14]([O:20][CH3:21])=[CH:15][C:16]([O:18][CH3:19])=[CH:17][C:11]=2[O:10][CH3:9])=[O:41])[N:35]=1)[CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH3:33]
Reactant: CCCCCCCCCCCCc1cnn(C(C(=O)O)c2ccccc2)n1
Reactant: COc1cc(OC)c(N)c(OC)c1
Agent: C(=NC1CCCCC1)=NC1CCCCC1
Agent: Cl
Solvent: ClCCl
Solvent: C1CCOC1
Solvent: CCN(CC)CC
Product: CCCCCCCCCCCCc1cnn(C(C(=O)Nc2c(OC)cc(OC)cc2OC)c2ccccc2)n1
Temperature: 25 °C
Reaction time: 1 h
Yield: 74.5 %

Procedure:
Triethylamine (1.2 mL, 8.4 mmol) was added to a suspension of 2,4,6-trimethoxyaniline hydrochloride (1.68 g, 7.7 mmol) in 100 mL THF and stirred for 1 hour before filtering to remove triethylamine hydrochloride. The filtrate was concentrated and redissolved in 100 mL dichloromethane along with (±)-4-dodecyl-α-phenyl-2H-1,2,3-triazole-2-acetic acid (2.59 g, 7.0 mmol) at 0° C. Dicyclohexylcarbodiimide (1.51 g, 7.3 mmol) was added in one portion and the resulting suspension was warmed to room temperature and stirred for 16 hours. Filtered to remove a white solid and partitioned the filtrate between chloroform and 1N HCl. The organic layer was dried over MgSO4, filtered, and concentrated to give a pale lavender solid. Recrystallization from ethyl acetate/hexanes (4:1) gave the title compound as a white solid (2.80 g, 75%); mp 123°-125° C.