Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [CH3:1][C:2]1([CH3:19])[CH2:7][O:6][P:5]([CH2:9][C:10]2[CH:18]=[CH:17][C:13]([C:14](O)=[O:15])=[CH:12][CH:11]=2)(=[O:8])[O:4][CH2:3]1.C(OC(=O)[NH:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]2[S:34][CH:35]=[CH:36][CH:37]=2)=[CH:29][C:28]=1[NH2:38])(C)(C)C.C(Cl)CCl.C1C=CC2N(O)N=NC=2C=1.CCN(C(C)C)C(C)C>CN(C=O)C>[NH2:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]2[S:34][CH:35]=[CH:36][CH:37]=2)=[CH:29][C:28]=1[NH:38][C:14](=[O:15])[C:13]1[CH:17]=[CH:18][C:10]([CH2:9][P:5]2(=[O:8])[O:6][CH2:7][C:2]([CH3:19])([CH3:1])[CH2:3][O:4]2)=[CH:11][CH:12]=1
Reactant: CC1(C)COP(=O)(Cc2ccc(C(=O)O)cc2)OC1
Reactant: CC(C)(C)OC(=O)Nc1ccc(-c2cccs2)cc1N
Agent: On1nnc2ccccc21
Solvent: ClCCCl
Solvent: CCN(C(C)C)C(C)C
Solvent: CN(C)C=O
Product: CC1(C)COP(=O)(Cc2ccc(C(=O)Nc3cc(-c4cccs4)ccc3N)cc2)OC1
Temperature: 25 °C
Reaction time: 18 h

Procedure:
4-(5,5-Dimethyl-2-oxo-2λ5-[1,3,2]dioxaphosphinan-2-ylmethyl)-benzoic acid (100 mg, 0.35 mmol), (2-amino-4-thiophen-2-yl-phenyl)-carbamic acid tert-butyl ester (123 mg, 0.42 mmol), EDC (81 mg, 0.42 mmol), HOBT (54 mg, 0.35 mmol), and DIPEA (136 mg, 1.05 mmol) were combined and diluted with DMF (1.4 mL). The resulting mixture was stirred at ambient temperature for 18 hours. The reaction mixture was purified directly by HPLC (20-85% MeCN in water w/0.025% TFA). Pure fractions were identified, combined and concentrated in vacuo. The residue was diluted with 10:1 DCM:TFA and stirred at ambient temperature for 2 hours. The mixture was then concentrated in vacuo to afford the title compound: 1H NMR (DMSO-d6, 600 MHz) δ 9.85 (s, 1H), 7.93 (d, J=7.2 Hz, 2H), 7.50 (s, 1H), 7.43 (d, J=7.2 Hz, 2H), 7.34-7.40 (m, 2H), 7.28-7.30 (m, 1H), 7.03-7.06 (m, 1H), 6.90-6.92 (m, 1H), 4.20-4.25 (m, 2H), 4.01 (br-s, 2H), 3.87-3.94 (m, 2H), 3.52 (d, J=20.4 Hz, 2H), 1.08 (s, 3H), 0.84 (s, 3H). MS: cal'd 457 (MH+), exp 457 (MH+).
Reaction SMILES: [CH3:1][S:2][C:3]1[N:4]=[C:5]([NH:14][C:15]2[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:24])([F:23])[F:22])[CH:16]=2)[C:6]2[C:12](=[O:13])[NH:11][CH:10]=[CH:9][C:7]=2[N:8]=1.[Br:25]N1C(=O)CCC1=O>CN(C=O)C>[Br:25][C:9]1[C:7]2[N:8]=[C:3]([S:2][CH3:1])[N:4]=[C:5]([NH:14][C:15]3[CH:20]=[CH:19][CH:18]=[C:17]([C:21]([F:22])([F:24])[F:23])[CH:16]=3)[C:6]=2[C:12](=[O:13])[NH:11][CH:10]=1
Reactant: O=C1CCC(=O)N1Br
Reactant: CSc1nc(Nc2cccc(C(F)(F)F)c2)c2c(=O)[nH]ccc2n1
Solvent: CN(C)C=O
Product: CSc1nc(Nc2cccc(C(F)(F)F)c2)c2c(=O)[nH]cc(Br)c2n1
Temperature: 25 °C
Reaction time: 2 h

Procedure:
A 20 mL reaction vessel was charged with 2-(methylthio)-4-(3-(trifluoromethyl)phenylamino)pyrido[4,3-d]pyrimidin-5(6H)-one (135 mg, 0.38 mmol), and N-bromosuccinimide (68 mg, 0.38 mmol) in 7 mL dry DMF. The reaction mixture was stirred at room temperature for 2 hours. The solvent was removed under reduced pressuring yielding yellow residue. The residue was recrystallized from acetonitrile providing yellow solid (100 mg, 74%). MS m/z: 431, 433 (M+H)+.
Reaction SMILES: Br[C:2]1[C:10]2[N:9]3[C@H:11]([CH3:16])[CH2:12][NH:13][C:14](=[O:15])[C:8]3=[CH:7][C:6]=2[CH:5]=[C:4]([F:17])[CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH2:24](B(CC)CC)[CH3:25].O>CN(C)C=O.O1CCCC1>[CH2:24]([C:2]1[C:10]2[N:9]3[C@H:11]([CH3:16])[CH2:12][NH:13][C:14](=[O:15])[C:8]3=[CH:7][C:6]=2[CH:5]=[C:4]([F:17])[CH:3]=1)[CH3:25]
Reactant: C[C@@H]1CNC(=O)c2cc3cc(F)cc(Br)c3n21
Reactant: CCB(CC)CC
Agent: O=C([O-])[O-]
Agent: [Cs+]
Solvent: O
Solvent: CN(C)C=O
Solvent: C1CCOC1
Product: CCc1cc(F)cc2cc3n(c12)[C@H](C)CNC3=O
Temperature: 50 °C

Procedure:
6.2 g (R)-6-bromo-8-fluoro-4-methyl-3,4-dihydro-2H-pyrazino[1,2-a]indol-1-one was dissolved in 150 ml N,N-dimethylformamide under argon. 1.43 g (Dppf)PdCl2, 39 g caesium carbonate and 41.6 ml of a 1M solution of triethylborane in tetrahydrofuran were added. The mixture was heated 15 h at 50° C., allowed to cool to room temperature and poured into water. The aqueous mixture was extracted with ethyl acetate. The combined organic phases washed with brine, dried over magnesium sulfate and evaporated. The residue was purified by column chromatography on reversed phase silica gel (6:4 to 3:7 water/methanol) to afford the title product as an off-white solid. Yield: 1.8 g. ISP-MS: m/e 247.3 ([M+H]+).
Reaction SMILES: [Na].[C:2]1([O:9][CH3:10])[C:3](=[CH:5][CH:6]=[CH:7][CH:8]=1)[OH:4].[CH2:11]([O:13][C:14](=[O:22])[CH:15](Cl)[C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH3:12]>C(O)C>[CH2:11]([O:13][C:14](=[O:22])[CH:15]([O:4][C:3]1[CH:5]=[CH:6][CH:7]=[CH:8][C:2]=1[O:9][CH3:10])[C:16]([O:18][CH2:19][CH3:20])=[O:17])[CH3:12]
Reactant: CCOC(=O)C(Cl)C(=O)OCC
Reactant: COc1ccccc1O
Agent: [Na]
Solvent: CCO
Product: CCOC(=O)C(Oc1ccccc1OC)C(=O)OCC
Temperature: 25 °C
Reaction time: 72 h

Procedure:
To a solution of 6.9 g (0.3 mole) of sodium pellets dissolved in 400 ml of absolute ethanol was successively added a solution of 37.9 g (0.305 mole) of guaiacol in 50 ml of ethanol followed by a solution of 68.1 g (0.35 mole) of diethylchloromalonate in 50 ml of ethanol. The mixture was heated at reflux for 28 hr and then stirred at ambient temperature for 3 days. The mixture was filtered and the filtrate was concentrated. The residue was partitioned between salt water and ethyl ether. The layers were separated and the aqueous layer was extracted twice with 150 ml portions of ethyl ether. The combined organic layers were washed with brine, dried (sodium sulfate0 and concentrated to give a yellow oil. The oil was subjected to vacuum distillation and 66.6 g (79%) of the title compound was collected as a clear oil, bp 136°-153° C. at 0.3 mm.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:4]=1[CH2:5][NH:6][C:7]1[S:8][CH:9]=[CH:10][N:11]=1.COC1C=C(OC)C=CC=1CN(C1SN=CN=1)[S:24]([C:27]1[CH:36]=[CH:35][C:30]2[NH:31][C:32](=[O:34])[O:33][C:29]=2[CH:28]=1)(=[O:26])=[O:25]>C1COCC1>[CH3:1][O:2][C:3]1[CH:15]=[C:14]([O:16][CH3:17])[CH:13]=[CH:12][C:4]=1[CH2:5][N:6]([C:7]1[S:8][CH:9]=[CH:10][N:11]=1)[S:24]([C:27]1[CH:36]=[CH:35][C:30]2[NH:31][C:32](=[O:34])[O:33][C:29]=2[CH:28]=1)(=[O:26])=[O:25]
Reactant: COc1ccc(CNc2nccs2)c(OC)c1
Reactant: COc1ccc(CN(c2ncns2)S(=O)(=O)c2ccc3[nH]c(=O)oc3c2)c(OC)c1
Solvent: C1CCOC1
Product: COc1ccc(CN(c2nccs2)S(=O)(=O)c2ccc3[nH]c(=O)oc3c2)c(OC)c1
Temperature: 25 °C
Reaction time: 0.5 h

Procedure:
A solution of 41-2 (2.79 g, 11.13 mmol) in THF (71 mL) was cooled to −78° C. Lithium hexamethyldisilizane (LHMDS, 21.4 ml, 21.4 mmol, 1.0M in THF) was added and the reaction was allowed to warm to RT and stir for 30 minutes. Commercially-available, solid 1-5 (4 g, 17.12 mmol) was then added in portions, maintaining the temperature of the reaction mixture at −78° C. The reaction was allowed to slowly warm to RT. After reaching RT, the reaction was quenched with saturated ammonium chloride solution at 0° C. and extracted into EtOAc (3×150 mL). The combined organic layers were washed with brine, dried over sodium sulfate, filtered and concentrated. Purification by normal phase chromatography (0-60% EtOAc in hexane) yielded 41-3 as a solid.