Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([NH2:11])[CH2:9][CH3:10])=[C:4]([F:12])[C:3]=1[C:13]([C:15]1[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=1)=[O:14].[N:21]1([C:31]([O:33][C:34]([CH3:37])([CH3:36])[CH3:35])=[O:32])[CH2:25][CH:24]=[C:23]([C:26](OCC)=[O:27])[CH2:22]1.C(N=C=NCCCN(C)C)C.ON1C2N=CC=CC=2N=N1.C(N(CC)CC)C>C(Cl)Cl>[C:34]([O:33][C:31]([N:21]1[CH2:25][CH:24]=[C:23]([C:26](=[O:27])[NH:11][C@H:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[C:3]([C:13]([C:15]3[CH:16]=[N:17][CH:18]=[CH:19][CH:20]=3)=[O:14])[C:4]=2[F:12])[CH2:9][CH3:10])[CH2:22]1)=[O:32])([CH3:37])([CH3:36])[CH3:35]
Reactant: CCOC(=O)C1=CCN(C(=O)OC(C)(C)C)C1
Reactant: CC[C@H](N)c1ccc(Cl)c(C(=O)c2cccnc2)c1F
Agent: CCN=C=NCCCN(C)C
Agent: On1nnc2cccnc21
Solvent: ClCCl
Solvent: CCN(CC)CC
Product: CC[C@H](NC(=O)C1=CCN(C(=O)OC(C)(C)C)C1)c1ccc(Cl)c(C(=O)c2cccnc2)c1F
Reaction time: 18 h
Yield: 85.4 %

Procedure:
To (1S)-1-{4-chloro-2-fluoro-3-[(pyridin-3-yl)carbonyl]phenyl}propan-1-amine (0.1 g, 0.3 mmol) (Example 26) in DCM was added 1-tert-butyl 3-ethyl 1H-pyrrole-1,3(2H,5H)-dicarboxylate (0.065, 0.3 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (0.07 mg, 0.36 mmol), 1-hydroxy-7-azabenzotriazole (0.049 g, 0.36 mmol) and triethylamine (0.085 ml, 0.6 mmol), then stirred at ambient for 18 hours. The reaction was diluted with DCM washed with 5% citric acid, sat. sodium bicarbonate then brine. The organic extract was dried (Na2SO4), filtered and concentrated to give 3-{(S)-1-[4-Chloro-2-fluoro-3-(pyridine-3-carbonyl)-phenyl]-propylcarbamoyl}-2,5-dihydro-pyrrole-1-carboxylic acid tert-butyl ester (0.125 g). MS: [M+H]+ 488.
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[O:12][N:11]=[C:10]([CH3:13])[C:9]=2[NH2:14])=[CH:4][CH:3]=1.[C:15]1([CH2:21][CH2:22][C:23](=O)[CH3:24])[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=1>>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[O:12][N:11]=[C:10]([CH3:13])[C:9]=2[NH:14][CH:23]([CH3:24])[CH2:22][CH2:21][C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][CH:16]=2)=[CH:6][CH:7]=1
Reactant: Cc1noc(-c2ccc(Br)cc2)c1N
Reactant: CC(=O)CCc1ccccc1
Product: Cc1noc(-c2ccc(Br)cc2)c1NC(C)CCc1ccccc1

Procedure:
Prepared according to the procedure described in Example 24, Step 1, using 5-(4-bromo-phenyl)-3-methyl-isoxazol-4-ylamine and 4-phenyl-butan-2-one.
Reaction SMILES: [O:1]1[CH2:6][CH2:5][N:4]([C:7]([CH:9]2[CH2:14][CH2:13][NH:12][CH2:11][CH2:10]2)=[O:8])[CH2:3][CH2:2]1.[Cl:15][C:16]1[CH:17]=[N:18][CH:19]=[C:20]([Cl:23])[C:21]=1Cl.C(N(CC)CC)C>CN1C(=O)CCC1>[Cl:15][C:16]1[CH:17]=[N:18][CH:19]=[C:20]([Cl:23])[C:21]=1[N:12]1[CH2:13][CH2:14][CH:9]([C:7]([N:4]2[CH2:3][CH2:2][O:1][CH2:6][CH2:5]2)=[O:8])[CH2:10][CH2:11]1
Reactant: O=C(C1CCNCC1)N1CCOCC1
Reactant: Clc1cncc(Cl)c1Cl
Solvent: CN1CCCC1=O
Solvent: CCN(CC)CC
Product: O=C(C1CCN(c2c(Cl)cncc2Cl)CC1)N1CCOCC1
Yield: 36.3 %

Procedure:
General procedure C was followed using morpholino(piperidin-4-yl)methanone (21 mg, 0.12 mmol), 3,4,5-trichloropyridine (23 mg, 0.12 mmol), triethylamine (32 μL, 0.23 mmol) and NMP (1 mL). The crude product was purified by flash column chromatography on silica gel (hexane/EtOAc, 1:1) to furnish the title compound as a white solid (15 mg, 35%), m.p. 172-174° C.; umax (CHCl3)/cm−1 3006, 2858, 1632, 1559, 1448, 1116, 1020; m/z (ESI) C15H20Cl2N3O2 requires 344.0927, found [M+H]+ 344.0929.
Reaction SMILES: C([O-])(=O)C.[NH4+:5].[C:6]([NH:9][CH:10]([C:16](=O)[CH3:17])[C:11]([O:13][CH2:14][CH3:15])=[O:12])(=O)[CH3:7]>C(O)(=O)C>[CH3:7][C:6]1[NH:9][C:10]([C:11]([O:13][CH2:14][CH3:15])=[O:12])=[C:16]([CH3:17])[N:5]=1
Reactant: CCOC(=O)C(NC(C)=O)C(C)=O
Reactant: [NH4+]
Agent: CC(=O)[O-]
Solvent: CC(=O)O
Product: CCOC(=O)c1[nH]c(C)nc1C
Yield: 66.9 %

Procedure:
Ammonium acetate (185 mg, 2.4 mmol) was added to a solution of ethyl 2-(acetylamino)-3-oxobutanoate (90 mg, 0.48 mmol) in acetic acid (1.0 mL). The mixture was heated to reflux overnight. After cooling, the solvent was evaporated under reduced pressure and the residue was taken up in saturated sodium bicarbonate and extracted with EtOAc. The organic layer was dried over sodium sulfate, and concentrated. The residue was purified by column chromatography (0-4% 2M NH3 solution of MeOH in DCM) to give the title compound (54 mg, 67%) as a white solid. 1H NMR (400 MHz, CDCl3-d) δ ppm 4.30 (q, J=7.20 Hz, 2H) 2.44 (s, 3H) 2.38 (s, 3H) 1.34 (t, J=7.14 Hz, 3H). LCMS: m/z 169 (M+1).
Reaction SMILES: [N:1]1([C:12](=[O:13])[C:11]2[N:10]([CH2:14][CH2:15][CH2:16]Br)[CH:9]=[N:8][C:7]=2[N:5]([CH3:6])[C:3]1=[O:4])[CH3:2].[NH2:18][CH2:19][CH2:20][C:21]1[C:29]2[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=2)[NH:23][CH:22]=1.C(=O)([O-])[O-].[K+].[K+].[ClH:36]>CN(C)C=O.O.C(O)C>[N:1]1([C:12](=[O:13])[C:11]2[N:10]([CH2:14][CH2:15][CH2:16][NH:18][CH2:19][CH2:20][C:21]3[C:29]4[C:24](=[CH:25][CH:26]=[CH:27][CH:28]=4)[NH:23][CH:22]=3)[CH:9]=[N:8][C:7]=2[N:5]([CH3:6])[C:3]1=[O:4])[CH3:2].[ClH:36]
Reactant: NCCc1c[nH]c2ccccc12
Reactant: Cn1c(=O)c2c(ncn2CCCBr)n(C)c1=O
Agent: Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: CCO
Solvent: CN(C)C=O
Product: Cn1c(=O)c2c(ncn2CCCNCCc2c[nH]c3ccccc23)n(C)c1=O

Procedure:
A stirred mixture of 3-(theophyllin-7-yl)propyl bromide (3.0 g., 0.01 mole), tryptamine base (1.60; 0.01 mole) and potassium carbonate (4 g; 0.029 mole) in dry dimethylformamide (50 cc.) was heated, under a dry nitrogen blanket, in an oil-bath maintained at 75° for 17.5 hours. After cooling, the dark mixture was diluted with water (200 cc.) and extracted with dichloromethane (2×50 cc.). The combined extracts were washed with water (2×100 cc.) and dried (MgSO4). Filtration and evaporation gave a syrup which was dissolved in a little ethanol and acidified with ethanolic hydrogen chloride. After cooling, the precipitated crystals were filtered off and washed well with ethanol and ethyl acetate to give the title compound hydrochloride, m.p. 273°-274° C. (dec.) (partial decomposition above 265° C.). The product may also be designated as 3,7-dihydro-7-[3-[[2-(1H-indol-3-yl)ethyl]amino]propyl]-1,3-dimethyl-1H-purine-2,6-dione,hydrochloride. The yield was 1.99 g.