Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [NH:1]([C:7]([O:9][CH2:10][C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1)=[O:8])[C@H:2]([C:4]([OH:6])=[O:5])[CH3:3]>C1COCC1>[CH2:10]([O:5][C:4](=[O:6])[C@H:2]([CH3:3])[NH:1][C:7]([O:9][CH2:10][C:11]1[CH:12]=[CH:13][CH:14]=[CH:15][CH:16]=1)=[O:8])[C:11]1[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=1
Reactant: C[C@H](NC(=O)OCc1ccccc1)C(=O)O
Solvent: C1CCOC1
Product: C[C@H](NC(=O)OCc1ccccc1)C(=O)OCc1ccccc1
Temperature: 45 °C

Procedure:
CBZ-Ala (10, 0.825 g, 0.0037 mol) was added to a solution of 2 (R=Bn, 2.8 g, 200 mol %) in 15 mL of THF. The reaction was heated at 45° C. for 20 h, after which the reaction was cooled, evaporated and following the general procedure gave 16 as a clear oil, 1.07 g, 92%: [α]25D -31.7° (c 1.1, EtOH); IR 3340, 3060, 3030, 1720; 1H NMR δ 7.45-7.28 (m, 10H), 5.43 (d, 1H, J=7), 5.15-5.08 (m, 4H), 4.43-4.40 (m, 1H), 1.38 (d, 3H, J=7.1). Anal. Calcd for C18H19NO4 : C, 69.0; H, 6.1,; N, 4.5. Found: C, 69.3; H, 6.2; N, 4.7.
Reaction SMILES: C([N-]C(C)C)(C)C.[Li+].[CH3:9][C:10]1[CH:15]=[N:14][CH:13]=[CH:12][N:11]=1.[CH3:16][O:17][C:18]1[CH:27]=[CH:26][C:21]([CH:22]=[CH:23][CH:24]=[O:25])=[CH:20][CH:19]=1>O1CCCC1>[OH:25][CH:24]([CH:23]=[CH:22][C:21]1[CH:20]=[CH:19][C:18]([O:17][CH3:16])=[CH:27][CH:26]=1)[CH2:9][C:10]1[CH:15]=[N:14][CH:13]=[CH:12][N:11]=1
Reactant: Cc1cnccn1
Reactant: COc1ccc(C=CC=O)cc1
Agent: CC(C)[N-]C(C)C
Agent: [Li+]
Solvent: C1CCOC1
Product: COc1ccc(C=CC(O)Cc2cnccn2)cc1
Temperature: 25 °C

Procedure:
To a solution of lithium diisopropylamide (1.5 Molar, 73.3 mL, 0.11 mole) in 150 mL of tetrahydofuran at -78° C. is added slowly to a solution of 2-methylpyrazine (9.4 g, 0.1 mole) in 100 mL of tetrahydrofuran. The mixture is allowed to warm to room temperature and then cooled to -78° C. A solution of p-methoxycinnamaldehyde (17.8 g, 0.11 mole) in 100 mL of tetrahydrofuran is added dropwise over 15 minutes. The reaction product mixture is then worked up according to the procedure of Example I to provide the title compound.
Reaction SMILES: C(=O)([O-])[O-].[Cs+].[Cs+].[OH:7][C:8]1[CH:13]=[CH:12][C:11]([CH:14]([C:21]2[CH:25]=[CH:24][O:23][N:22]=2)[CH2:15][C:16]([O:18]CC)=[O:17])=[CH:10][CH:9]=1.[Cl:26][C:27]1[C:28]([CH3:41])=[C:29]([C:33]2[CH:34]=[C:35]([CH:38]=[CH:39][CH:40]=2)[CH2:36]Cl)[CH:30]=[CH:31][CH:32]=1.[I-].[Cs+]>CS(C)=O.[Cl-].[Na+].O.CCOC(C)=O>[Cl:26][C:27]1[C:28]([CH3:41])=[C:29]([C:33]2[CH:34]=[C:35]([CH:38]=[CH:39][CH:40]=2)[CH2:36][O:7][C:8]2[CH:9]=[CH:10][C:11]([CH:14]([C:21]3[CH:25]=[CH:24][O:23][N:22]=3)[CH2:15][C:16]([OH:18])=[O:17])=[CH:12][CH:13]=2)[CH:30]=[CH:31][CH:32]=1
Reactant: Cc1c(Cl)cccc1-c1cccc(CCl)c1
Reactant: CCOC(=O)CC(c1ccc(O)cc1)c1ccon1
Agent: O=C([O-])[O-]
Agent: [Cl-]
Agent: [Cs+]
Solvent: O
Solvent: CS(C)=O
Solvent: CCOC(C)=O
Product: Cc1c(Cl)cccc1-c1cccc(COc2ccc(C(CC(=O)O)c3ccon3)cc2)c1
Temperature: 35 °C
Reaction time: 4 h
Yield: 44.7 %

Procedure:
Cesium carbonate (80 mg, 0.24 mmol) was added to a mixture of 1.1 (50 mg, 0.2 mmol), the benzyl chloride 1.4 (60 mg, 0.24 mmol) and CsI (catalytic amount) in DMSO (1 mL). The mixture was stirred at room temperature for 2 hours and at 35° C. for 4 hours. After cooling, the mixture was treated with EtOAc (5 mL) and brine (5 mL). The organic layer was separated, washed twice with brine, dried, and concentrated. The crude product was treated with THF (2 mL), MeOH (2 mL), water (1 mL) and NaOH (0.1 mL, 10 N). The mixture was stirred at room temperature for 4 hours. The organic solvent was blown away by nitrogen, and the aqueous mixture was acidified by adding HCl (0.35 mL, 3 N). The aqueous was extracted with DCM. The organic layer was dried, concentrated, and purified by flash chromatography to give 1 (40 mg). MS ESI (pos.) m/e: 448 (M+H). 1H NMR (CDCl3) δ 8.29 (d, 1H), 7.40 (m, 4H), 7.25 (m, 2H), 7.18 (m, 4H), 6.95 (d, 2H), 6.08 (d, 1H), 5.10 (s, 2H), 4.57 (t, 1H), 3.28 (dd, 1H), 2.99 (dd, 1H), 2.26 (s, 3H).
Reaction SMILES: [Cl:1][C:2]1[C:7](=[O:8])[C:6]([OH:9])=[CH:5][N:4]([CH3:10])[C:3]=1[CH3:11].C(=O)([O-])[O-].[K+].[K+].C[O:19][CH:20](O)[C:21]([F:24])([F:23])[F:22]>CO>[Cl:1][C:2]1[C:7](=[O:8])[C:6]([OH:9])=[C:5]([CH:20]([OH:19])[C:21]([F:24])([F:23])[F:22])[N:4]([CH3:10])[C:3]=1[CH3:11]
Reactant: COC(O)C(F)(F)F
Reactant: Cc1c(Cl)c(=O)c(O)cn1C
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: Cc1c(Cl)c(=O)c(O)c(C(O)C(F)(F)F)n1C
Temperature: 120 °C
Reaction time: 2.5 h
Yield: 85 %

Procedure:
3-Chloro-5-hydroxy-1,2-dimethylpyridin-4(1H)-one (500 mg, 2.80 mmol) was suspended in trifluoroacetaldehyde methyl hemiacetal (3 mL). Potassium carbonate (119 mg, 0.86 mmol) was added and the mixture was heated to 120° C. After 2.5 hours, the reaction mixture was allowed to cool to room temperature, then diluted with methanol and filtered. The filtrate was concentrated to dryness and diluted with acetone. The solution was filtered and the filtrate was concentrated to give 3-chloro-5-hydroxy-1,2-dimethyl-6-(2,2,2-trifluoro-1-hydroxyethyl)pyridin-4(1H)-one (650 mg) as a pink solid. Yield=85%; 1H-NMR (MeOD-D4, 90 MHz) δ (ppm): 5.9 (q, J=9.1 Hz, 1H), 4.01 (s, 3H) and 2.65 (s, 3H); MS-ESI m/z 272 [M+1]+.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([C:9]2([CH2:28][CH2:29]CS([O-])(=O)=O)[CH2:13][CH2:12][N:11]([C:14](=[O:27])[C:15]3[CH:20]=[C:19]([O:21][CH3:22])[C:18]([O:23][CH3:24])=[C:17]([O:25][CH3:26])[CH:16]=3)[CH2:10]2)[CH:5]=[CH:6][C:7]=1[Cl:8].Cl.[CH2:36]([N:43]1[C:47](=[O:48])[C:46]2([CH2:53][CH2:52][NH:51][CH2:50][CH2:49]2)[N:45]([C:54]2[CH:59]=[CH:58][C:57]([F:60])=[CH:56][CH:55]=2)[C:44]1=[O:61])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>>[CH2:36]([N:43]1[C:47](=[O:48])[C:46]2([CH2:53][CH2:52][N:51]([CH2:29][CH2:28][C:9]3([C:4]4[CH:5]=[CH:6][C:7]([Cl:8])=[C:2]([Cl:1])[CH:3]=4)[CH2:13][CH2:12][N:11]([C:14](=[O:27])[C:15]4[CH:20]=[C:19]([O:21][CH3:22])[C:18]([O:23][CH3:24])=[C:17]([O:25][CH3:26])[CH:16]=4)[CH2:10]3)[CH2:50][CH2:49]2)[N:45]([C:54]2[CH:55]=[CH:56][C:57]([F:60])=[CH:58][CH:59]=2)[C:44]1=[O:61])[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1
Reactant: COc1cc(C(=O)N2CCC(CCCS(=O)(=O)[O-])(c3ccc(Cl)c(Cl)c3)C2)cc(OC)c1OC
Reactant: O=C1N(Cc2ccccc2)C(=O)C2(CCNCC2)N1c1ccc(F)cc1
Agent: Cl
Product: COc1cc(C(=O)N2CCC(CCN3CCC4(CC3)C(=O)N(Cc3ccccc3)C(=O)N4c3ccc(F)cc3)(c3ccc(Cl)c(Cl)c3)C2)cc(OC)c1OC

Procedure:
Prepare by the method of example 3.3 using 2-[3-(3,4-dichloro-phenyl)-1-(3,4,5-trimethoxy-benzoyl)-pyrrolidin-3-yl]-ethyl-methanesulfonate (5 mmol) and 3-benzyl-1-(4-fluoro-phenyl)-1,3,8-triaza-spiro[4.5]decane-2,4-dione hydrochloride (7.5 mmol, 1.5 eq.). Chromatograph on silica gel to give the title compound.
Reaction SMILES: [CH3:1][CH:2]([CH3:16])[CH2:3][NH:4][C:5]1[CH:10]=[C:9]([C:11]([F:14])([F:13])[F:12])[CH:8]=[CH:7][C:6]=1[CH3:15].Cl[S:18]([C:21]1[CH:26]=[CH:25][C:24]([CH2:27][CH2:28][C:29]([O:31][CH3:32])=[O:30])=[CH:23][CH:22]=1)(=[O:20])=[O:19]>N1C=CC=CC=1>[CH3:1][CH:2]([CH3:16])[CH2:3][N:4]([C:5]1[CH:10]=[C:9]([C:11]([F:12])([F:13])[F:14])[CH:8]=[CH:7][C:6]=1[CH3:15])[S:18]([C:21]1[CH:22]=[CH:23][C:24]([CH2:27][CH2:28][C:29]([O:31][CH3:32])=[O:30])=[CH:25][CH:26]=1)(=[O:20])=[O:19]
Reactant: Cc1ccc(C(F)(F)F)cc1NCC(C)C
Reactant: COC(=O)CCc1ccc(S(=O)(=O)Cl)cc1
Solvent: c1ccncc1
Product: COC(=O)CCc1ccc(S(=O)(=O)N(CC(C)C)c2cc(C(F)(F)F)ccc2C)cc1
Reaction time: 0.5 h

Procedure:
To a solution of (2-methylpropyl)[2-methyl-5-(trifluoromethyl)phenyl]amine (50 mg, 0.216 mmol) in pyridine (5 mL) was added methyl 3-[4-(chlorosulfonyl)phenyl]propanoate (56.8 mg, 0.216 mmol). The mixture was stirred for 30 minutes to ensure dilution, then stood at room temperature, in air, for 16 hours. The solvent was evaporated in vacuo to give the crude product which was purified by MDAP (Method F) to give the required product, 21.5 mg. LCMS (M+1) 458, RT 1.39 mins.