Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Br:1][C:2]1[CH:7]=[CH:6][C:5]([C:8](=[O:20])[CH2:9][C:10]([CH2:17][CH2:18][CH3:19])([C:14]([O-:16])=[O:15])C([O-])=O)=[CH:4][CH:3]=1.[CH3:21][C:22](C)=O.[OH-].[Na+]>C(O)C>[Br:1][C:2]1[CH:3]=[CH:4][C:5]([C:8](=[O:20])[CH2:9][CH:10]([CH2:17][CH2:18][CH3:19])[C:14]([O:16][CH2:21][CH3:22])=[O:15])=[CH:6][CH:7]=1
Reactant: CC(C)=O
Reactant: CCCC(CC(=O)c1ccc(Br)cc1)(C(=O)[O-])C(=O)[O-]
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: CCCC(CC(=O)c1ccc(Br)cc1)C(=O)OCC
Temperature: 55 °C
Reaction time: 0.25 h
Yield: 20 %

Procedure:
To a 200 mL flask was added crude 2-[2-(4-bromophenyl)-2-oxoethyl]-2-propylmalonate (7.62 g, 19.2 mmol), acetone (21 mL), and ethanol (19 mL), followed by addition of 1 N aqueous sodium hydroxide solution (19.1 mL). The reaction mixture was heated to 55° C. for 3 h. The clear, orange-red reaction mixture was then concentrated under reduced pressure and the residue was redissolved in dimethoxyethane (30 mL). The mixture was heated to 80° C. for 3 h. The reaction mixture was cooled to rt, diluted with ethyl acetate (100 mL) and water (100 mL), and stirred for 15 minutes until almost all color was extracted into the organic layer. The layers were separated and the aqueous layer extracted with additional ethyl acetate (75 mL). The combined organic layers were washed with saturated aqueous sodium chloride solution (75 mL), dried over anhydrous sodium sulfate, and concentrated under reduced pressure to afford an orange oil. The crude product was purified by flash chromatography (10:1 hexane:ethyl acetate) to afford ethyl 2-[2-(4-bromophenyl)-2-oxoethyl]pentanoate (1.33 g, 20%). LC-MS ret. time 3.60 min, m/z 326.05 (MH+); 1H NMR (300 MHz, CDCl3) δ 0.87 (t, 3H), 1.25 (t, 3H), 1.29-1.43 (m, 2H), 1.57-1.73 (m, 2H), 2.90-3.08 (m, 2H), 3.34-3.47 (m, 2H), 4.15 (q, 21), 7.59 (d, 4), 7.82 (d, 2H).
Reaction SMILES: [C:1]1([CH:11]=[C:12]2[CH2:17][C:16](=[O:18])[O:15][C:13]2=[O:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1.[NH:19]1[CH2:24][CH2:23][O:22][CH2:21][CH2:20]1>ClCCl>[C:1]1([CH:11]=[C:12]([CH2:17][C:16]([N:19]2[CH2:24][CH2:23][O:22][CH2:21][CH2:20]2)=[O:18])[C:13]([OH:15])=[O:14])[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][CH:9]=2)[CH:4]=[CH:3][CH:2]=1
Reactant: O=C1CC(=Cc2cccc3ccccc23)C(=O)O1
Reactant: C1COCCN1
Solvent: ClCCl
Product: O=C(O)C(=Cc1cccc2ccccc12)CC(=O)N1CCOCC1
Yield: 80.5 %

Procedure:
A solution of 1.00 g of 2-(1-naphthylmethylene)succinic anhydride and 0.37 g of morpholine in 31 ml of dry dichloromethane was stirred for 2 hours at room temperature. The reaction mixture was evaporated under reduced pressure, and the residue was crystallized from a mixture of ethyl acetate, benzene and hexane (1:1:1) to obtain 1.10 g of 2-(1-naphthylmethylene)-3(morpholinocarbonyl)propionic acid as colorless crystals. A solution of 1.00 g of the propionic acid compound was hydrogenated over 0.1 g of a 10% palladium charcoal under a hydrogen atmosphere. After filtration of the catalyst, the filtrate was evaporated under reduced pressure. The residue was crystallized from hexane to give 0.90 g of 2-(1-naphthylmethyl)-3(morpholinocarbonyl)propionic acid as a white powder.
Reaction SMILES: [F:1][C:2]([F:12])([F:11])[C:3]1[CH:8]=[CH:7][C:6]([NH2:9])=[C:5]([NH2:10])[CH:4]=1.[C:13](OCC)(=[O:17])[C:14]([O-])=[O:15]>>[F:1][C:2]([F:11])([F:12])[C:3]1[CH:4]=[C:5]2[C:6](=[CH:7][CH:8]=1)[NH:9][C:14](=[O:15])[C:13](=[O:17])[NH:10]2
Reactant: CCOC(=O)C(=O)[O-]
Reactant: Nc1ccc(C(F)(F)F)cc1N
Product: O=c1[nH]c2ccc(C(F)(F)F)cc2[nH]c1=O
Temperature: 25 °C

Procedure:
4-Trifluoromethyl-o-phenylenediamine (8.0 grams) was added to 80 ml. of ethyl oxalate and the resulting mixture was heated to reflux and refluxed for two hours. A precipitate formed during this period. The reaction mixture was then cooled to room temperature and filtered to separate the precipitate, m.p. 344°-346°C. (dec.) The product was identified as the expected 6-trifluoromethyl- 2(1H), 3(4H)-quinoxalinedione, by IR, TLC, NMR, and microanalysis.
Reaction SMILES: [CH2:1]([C:4]1[C:12]2[O:11][N:10]=[C:9]([CH2:13][CH2:14][C:15]3[N:16]=[C:17]([C:23]4[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=4[Cl:30])[O:18][C:19]=3[CH:20]([CH3:22])[CH3:21])[C:8]=2[CH:7]=[CH:6][C:5]=1[OH:31])[CH:2]=[CH2:3].Br[C:33]([CH3:40])([CH3:39])[C:34]([O:36][CH2:37][CH3:38])=[O:35].C(=O)([O-])[O-].[K+].[K+]>C(C(C)=O)C>[CH2:1]([C:4]1[C:12]2[O:11][N:10]=[C:9]([CH2:13][CH2:14][C:15]3[N:16]=[C:17]([C:23]4[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][C:24]=4[Cl:30])[O:18][C:19]=3[CH:20]([CH3:22])[CH3:21])[C:8]=2[CH:7]=[CH:6][C:5]=1[O:31][C:33]([CH3:40])([CH3:39])[C:34]([O:36][CH2:37][CH3:38])=[O:35])[CH:2]=[CH2:3]
Reactant: C=CCc1c(O)ccc2c(CCc3nc(-c4ccc(Cl)cc4Cl)oc3C(C)C)noc12
Reactant: CCOC(=O)C(C)(C)Br
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CCC(C)=O
Product: C=CCc1c(OC(C)(C)C(=O)OCC)ccc2c(CCc3nc(-c4ccc(Cl)cc4Cl)oc3C(C)C)noc12
Yield: 87.5 %

Procedure:
7-Allyl-6-hydroxy-3-[2-[2-(2,4-dichlorophenyl)-5-isopropyl-4-oxazolyl]ethyl]-1,2-benzisoxazole (92 mg, 0.20 mmol), ethyl 2-bromo-2-methylpropionate (196 mg, 1.00 mmol) and potassium carbonate (138 mg, 1.00 mmol) were suspended in methyl ethyl ketone (5.0 mL). The suspension was refluxed for 20 hours, and allowed to room temperature. After insoluble was filtered off, the filter cake was washed with methyl ethyl ketone. The filtrate and washings were combined, and concentrated. The residue was purified by column chromatography on silica gel with hexane/ethyl acetate (5/1) to give the desired compound (100 mg) as colorless oil (quantitative yield).
Reaction SMILES: Cl[C:2]1[CH:7]=[CH:6][NH:5][C:4](=[O:8])[C:3]=1[C:9]1[NH:10][C:11]2[C:12]([N:28]=1)=[CH:13][C:14]1[CH2:15][N:16]([CH2:21][CH2:22][N:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[C:17](=[O:20])[C:18]=1[CH:19]=2.[Br:29][C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=1[CH2:37][C@@H:38]([NH2:40])[CH3:39].CCN(C(C)C)C(C)C>CCO>[Br:29][C:30]1[CH:35]=[CH:34][C:33]([F:36])=[CH:32][C:31]=1[CH2:37][C@@H:38]([NH:40][C:2]1[CH:7]=[CH:6][NH:5][C:4](=[O:8])[C:3]=1[C:9]1[NH:10][C:11]2[C:12]([N:28]=1)=[CH:13][C:14]1[CH2:15][N:16]([CH2:21][CH2:22][N:23]3[CH2:27][CH2:26][CH2:25][CH2:24]3)[C:17](=[O:20])[C:18]=1[CH:19]=2)[CH3:39]
Reactant: C[C@H](N)Cc1cc(F)ccc1Br
Reactant: O=C1c2cc3[nH]c(-c4c(Cl)cc[nH]c4=O)nc3cc2CN1CCN1CCCC1
Solvent: CCN(C(C)C)C(C)C
Solvent: CCO
Product: C[C@@H](Cc1cc(F)ccc1Br)Nc1cc[nH]c(=O)c1-c1nc2cc3c(cc2[nH]1)C(=O)N(CCN1CCCC1)C3
Yield: 22.7 %

Procedure:
A solution of 2-(4-chloro-2-oxo-1,2-dihydropyridin-3-yl)-6-(2-pyrrolidin-1-ylethyl)-6,7-dihydroimidazo[4,5-f]isoindol-5(3H)-one (50 mg, 0.126 mmol), (1S)-2-(2-bromo-5-fluorophenyl)-1-methylethylamine (48 mg, 0.164 mmol) and DIEA (66 uL, 0.38 mmol) in 2 mL of EtOH was heated at 80° C. for 24 h. Then the solvent was evaporated and the residue was purified by column (silicagel, DCM:MeOH 9:1) to give 2-(4-((1S)-2-(2-bromo-5-fluorophenyl)-1-methylethylamino)-2-oxo-1,2-dihydropyridin-3-yl)-6-(2-pyrrolidin-1-ylethyl)-6,7-dihydroimidazo[4,5-f]isoindol-5(3H)-one (17 mg, 23%) as yellow solid. ESI-MS: m/z (MH+) 593.0. 1H NMR (300 MHz, CDCl3): δ 8.04 (d, J=58.6 Hz, 1H), 7.53 (d, J=80.9 Hz, 1H), 7.47 (m, 1H), 7.15 (m, 2H), 6.80 (m, 1H), 6.00 (m, 1H), 4.56 (m, 2H), 4.13 (m, 1H), 3.82 (m, 2H), 3.10 (m, 2H), 2.83 (m, 2H), 2.65 (m, 4H), 1.80 (m, 4H), 1.43 (d, J=6.60 Hz, 3H).