Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Cl:1][C:2]1[CH:10]=[C:9]2[C:5]([CH2:6][C:7](=[O:11])[NH:8]2)=[CH:4][CH:3]=1.[CH2:12]([O:14][C:15](=[O:29])[C:16]([O:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=1[CH:27]=O)([CH3:18])[CH3:17])[CH3:13].N1CCCC1>CO>[CH2:12]([O:14][C:15](=[O:29])[C:16]([O:19][C:20]1[CH:25]=[CH:24][C:23]([F:26])=[CH:22][C:21]=1/[CH:27]=[C:6]1\[C:7](=[O:11])[NH:8][C:9]2[C:5]\1=[CH:4][CH:3]=[C:2]([Cl:1])[CH:10]=2)([CH3:17])[CH3:18])[CH3:13]
Reactant: O=C1Cc2ccc(Cl)cc2N1
Reactant: CCOC(=O)C(C)(C)Oc1ccc(F)cc1C=O
Solvent: C1CCNC1
Solvent: CO
Product: CCOC(=O)C(C)(C)Oc1ccc(F)cc1/C=C1\C(=O)Nc2cc(Cl)ccc21
Temperature: 70 °C
Yield: 78.1 %

Procedure:
To the mixture of 6-chlorooxindole (5.3 g, 31.7 mmol) and 2-(4-fluoro-2-formyl-phenoxy)-2-methyl-propionic acid ethyl ester (8 g, 31.7 mmol) in methanol (30 mL) was added pyrrolidine (2.6 mL, 31.7 mmol) dropwise. Then the mixture was heated at 70° C. for 3 h. After cooled to room temperature, the mixture was filtered and the precipitate was collected, dried to give the title compound as a yellow solid (10 g).
Reaction SMILES: [N+:1]([C:4]1[CH:9]=[CH:8][C:7]([NH:10][C@H:11]([C:27]([OH:29])=[O:28])[CH2:12][CH2:13][CH2:14][CH2:15][NH:16]C(OCC2C=CC=CC=2)=O)=[CH:6][CH:5]=1)([O-])=O.O.[ClH:31]>C(O)C.[Pd]>[ClH:31].[ClH:31].[ClH:31].[NH2:1][C:4]1[CH:5]=[CH:6][C:7]([NH:10][C@H:11]([C:27]([OH:29])=[O:28])[CH2:12][CH2:13][CH2:14][CH2:15][NH2:16])=[CH:8][CH:9]=1
Reactant: O=C(NCCCC[C@H](Nc1ccc([N+](=O)[O-])cc1)C(=O)O)OCc1ccccc1
Agent: [Pd]
Agent: Cl
Solvent: CCO
Solvent: O
Product: NCCCC[C@H](Nc1ccc(N)cc1)C(=O)O
Reaction time: 0.75 h
Yield: 93 %

Procedure:
0.40 g (1 mmol) of Nα-(4-nitrophenyl)-Nε-(benzyloxycarbonyl)-L-lysine is dissolved in 20 ml of ethanol, 5 ml of water and 0.5 ml (3.5 eq) of 5N hydrochloric acid in a 250 ml glass reactor (Paar apparatus). 0.5 g of palladium-on-charcoal (50% moisture and 10% active) is then introduced. The mixture is hydrogenated under a pressure of approximately 2.76×105 Pa for 45 minutes and at a temperature of 12° C. After filtration through celite, the filtrate is evaporated. The purplish oily residue is taken up in ethanol and precipitated from a large volume of acetone with stirring. After filtration, 0.3 g of a white crystalline powder is obtained, i.e. a final yield of 93%.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[N:8]=[C:7]([CH3:12])[C:6]([CH2:13][P:14]([O:18][CH3:19])([O:16][CH3:17])=[O:15])=[CH:5]2.C(OOC(=O)C1C=CC=CC=1)(=O)C1C=CC=CC=1.[Br:38]N1C(=O)CCC1=O>C(Cl)(Cl)(Cl)Cl>[Br:38][CH2:12][C:7]1[C:6]([CH2:13][P:14]([O:16][CH3:17])([O:18][CH3:19])=[O:15])=[CH:5][C:4]2[C:9](=[CH:10][CH:11]=[C:2]([Cl:1])[CH:3]=2)[N:8]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: COP(=O)(Cc1cc2cc(Cl)ccc2nc1C)OC
Agent: O=C(OOC(=O)c1ccccc1)c1ccccc1
Solvent: ClC(Cl)(Cl)Cl
Product: COP(=O)(Cc1cc2cc(Cl)ccc2nc1CBr)OC
Yield: 73.4 %

Procedure:
A solution of 6-chloro-3-(dimethylphosphonomethyl)-2-methylquinoline (0.85 g, 2.7 mmol) in carbon tetrachloride (40 ml) was treated with benzoyl peroxide (100 mg) followed by N-bromosuccinimide (0.50 g, 2.8 mmol). The reaction mixture was refluxed for 4 hours, filtered and concentrated in vacuo. The residue was flash chromatographed on silica gel with ethyl acetate as the eluent to give 0.75 g of 2-bromomethyl-6-chloro-3-(dimethylphosphonomethyl)quinoline.
Reaction SMILES: [Li+].CCC[CH2-].[Cl:6][C:7]1[CH:13]=[C:12]([Cl:14])[CH:11]=[C:10]([Cl:15])[C:8]=1[NH2:9].[CH3:16][C:17]1[CH:22]=[C:21]([CH3:23])[N:20]2[N:24]=[C:25]([S:27](Cl)(=[O:29])=[O:28])[N:26]=[C:19]2[N:18]=1>CCCCCC.C1COCC1>[CH3:16][C:17]1[CH:22]=[C:21]([CH3:23])[N:20]2[N:24]=[C:25]([S:27]([NH:9][C:8]3[C:7]([Cl:6])=[CH:13][C:12]([Cl:14])=[CH:11][C:10]=3[Cl:15])(=[O:28])=[O:29])[N:26]=[C:19]2[N:18]=1
Reactant: Cc1cc(C)n2nc(S(=O)(=O)Cl)nc2n1
Reactant: Nc1c(Cl)cc(Cl)cc1Cl
Agent: [CH2-]CCC
Agent: [Li+]
Solvent: CCCCCC
Solvent: C1CCOC1
Product: Cc1cc(C)n2nc(S(=O)(=O)Nc3c(Cl)cc(Cl)cc3Cl)nc2n1
Temperature: -78 °C
Reaction time: 0.5 h
Yield: 21.2 %

Procedure:
A solution (10.7 ml, 17.1 mmol) of 1.60M N-butyllithium in hexane was added to a solution of 3.20 g (16.3 mmol) of 2,4,6-trichloroaniline in 20 ml of dry THF cooled to -78° C. The resultant solution was then allowed to warm to room temperature. This solution was added to a solution of 2.00 g (8.11 mmol) of 5,7-dimethyl-1,2,4-triazolo[1,5-a]pyrimidine-2-sulfonyl chloride in 30 ml of dry THF cooled to -10° C. The temperature of the reaction mixture was maintained between -13° C. and -9° C. during to course of the addition. After the addition was complete, the reaction mixture was stirred for 30 minutes and warmed to room temperature. After 1 hour at room temperature, THF was removed from the reaction mixture by evaporation. The residue was triturated with H2O and filtered. The filtrate was treated with charcoal and filtered through celite. The filtrate was washed with Et 2 O, and the aqueous phase was separated and acidified with 3N HCl to precipitate a solid. The solid was collected by filtration, washed with water and dried in vacuo to yield 0.70 g (21%) of the desired product as a tan solid, m.p. >200° C. (decomp.) 1H NMR and IR spectra were consistent with the assigned structure.
Reaction SMILES: [C:1]([C:4]1[CH:5]=[C:6]2[C:11](=[C:12]([CH2:15][CH2:16][CH3:17])[C:13]=1[OH:14])[N:10]=[C:9]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:8]=[C:7]2[NH:23][CH2:24][CH3:25])(=[O:3])[CH3:2].[C:26](OCC)(=O)[C:27]([O:29][CH2:30][CH3:31])=[O:28].CCOCC.[H-].[Na+]>CN(C)C=O.Cl.O>[CH2:24]([NH:23][C:7]1[C:6]2[C:11](=[C:12]([CH2:15][CH2:16][CH3:17])[C:13]3[O:14][C:26]([C:27]([O:29][CH2:30][CH3:31])=[O:28])=[CH:2][C:1](=[O:3])[C:4]=3[CH:5]=2)[N:10]=[C:9]([C:18]([O:20][CH2:21][CH3:22])=[O:19])[CH:8]=1)[CH3:25]
Reactant: CCOC(=O)C(=O)OCC
Reactant: CCCc1c(O)c(C(C)=O)cc2c(NCC)cc(C(=O)OCC)nc12
Agent: Cl
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Solvent: CCOCC
Solvent: O
Product: CCCc1c2nc(C(=O)OCC)cc(NCC)c2cc2c(=O)cc(C(=O)OCC)oc12
Reaction time: 72 h
Yield: 55 %

Procedure:
A mixture of the product of step (b) (2.2 g; 6.3953 mmoles) and diethyl oxalate (8.5 g; 58.2191 mole) in dry dimethylformamide (50 ml) was added slowly to a stirred suspension of ether washed sodium hydride (0.38 g, 15.83 mmole) under nitrogen. After the addition, the mixture was allowed to stir under nitrogen for 72 hours. The mixture was poured onto ice, followed by acidification with dilute hydrochloric acid. The pH of the mixture was adjusted to about 7 before extraction into ethyl acetate. The extract was washed with water, dried and evaporated to give a light yellow solid. The solid was dissolved in ethanolic hydrochloric acid and heated to reflux on a steambath for 3 hours. The mixture was cooled, and treated with water. This was then concentrated and the pH of the mixture was adjusted to about 7, followed by extraction with ethyl acetate. The extract was washed, dried and evaporated to give a brown solid (2 g; 74%). The solid was recrystallised from ethanol to give a light brown solid (1.5 g).
Reaction SMILES: Cl[C:2]1[N:21]=[C:5]2[C:6]([NH:10][C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[S:17]([CH3:20])(=[O:19])=[O:18])=[CH:7][CH:8]=[CH:9][N:4]2[N:3]=1.[CH3:22][N:23]1[CH2:28][CH2:27][CH:26]([C:29]2[CH:34]=[CH:33][C:32]([NH2:35])=[CH:31][CH:30]=2)[CH2:25][CH2:24]1.C1(P(C2CCCCC2)C2C=CC=CC=2C2C=CC=CC=2P(C2CCCCC2)C2CCCCC2)CCCCC1>>[CH3:20][S:17]([C:12]1[CH:13]=[CH:14][CH:15]=[CH:16][C:11]=1[NH:10][C:6]1[C:5]2[N:4]([N:3]=[C:2]([NH:35][C:32]3[CH:33]=[CH:34][C:29]([CH:26]4[CH2:25][CH2:24][N:23]([CH3:22])[CH2:28][CH2:27]4)=[CH:30][CH:31]=3)[N:21]=2)[CH:9]=[CH:8][CH:7]=1)(=[O:19])=[O:18]
Reactant: CN1CCC(c2ccc(N)cc2)CC1
Reactant: CS(=O)(=O)c1ccccc1Nc1cccn2nc(Cl)nc12
Agent: c1ccc(P(C2CCCCC2)C2CCCCC2)c(-c2ccccc2P(C2CCCCC2)C2CCCCC2)c1
Product: CN1CCC(c2ccc(Nc3nc4c(Nc5ccccc5S(C)(=O)=O)cccn4n3)cc2)CC1

Procedure:
N(8)-(2-Methanesulfonyl-phenyl)-N(2)-[4-(1-methyl-piperidin-4-yl)-phenyl]-[1,2,4]triazolo[1,5-a]pyridine-2,8-diamine was prepared from (2-chloro-[1,2,4]triazolo[1,5-a]pyridin-8-yl)-(2-methanesulfonyl-phenyl)-amine (75.0 mg, 0.232 mmol) and ]-4-(1-methyl-piperidin-4-yl)-phenylamine (53.0 mg, 0.279 mmol) with 2,2′-bis-dicyclohexylphosphanyl-biphenyl (25.0 mg, 0.0457 mmol) as the ligand in a manner analogous to Example 2d. Product isolated as a tan foam (0.063 g, 57%). 1H NMR (400 MHz, CDCl3, δ, ppm): 8.47 (s, 1H), 8.13 (d, J=6.8 Hz, 1H), 7.98 (dd, J=7.8, 1.2 Hz, 1H), 7.58-7.48 (m, 4H), 7.29-7.25 (m, 1H), 7.21 (d, J=8.4 Hz, 1H), 7.14-7.09 (m, 1H), 6.83-6.77 (m, 2H), 3.14 (s, 3H), 3.01-2.94 (m, 2H), 2.50-2.40 (m, 1H), 2.33 (s, 3H), 2.10-2.00 (m, 2H), 1.87-1.73 (m, 4H). MS=477 (MH)+.