Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: C([NH:5][S:6]([C:9]1[CH:14]=[CH:13][CH:12]=[C:11]([C:15]2[N:16]=[CH:17][N:18]([C:20]3[CH:25]=[C:24]([C:26]([F:29])([F:28])[F:27])[CH:23]=[C:22]([C:30]4[CH:35]=[CH:34][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:32][CH:31]=4)[N:21]=3)[CH:19]=2)[CH:10]=1)(=[O:8])=[O:7])(C)(C)C.C(O)(C(F)(F)F)=O>ClCCl>[F:29][C:26]([F:27])([F:28])[C:24]1[CH:23]=[C:22]([C:30]2[CH:31]=[CH:32][C:33]([C:36]([F:39])([F:38])[F:37])=[CH:34][CH:35]=2)[N:21]=[C:20]([N:18]2[CH:19]=[C:15]([C:11]3[CH:10]=[C:9]([S:6]([NH2:5])(=[O:8])=[O:7])[CH:14]=[CH:13][CH:12]=3)[N:16]=[CH:17]2)[CH:25]=1
Reactant: CC(C)(C)NS(=O)(=O)c1cccc(-c2cn(-c3cc(C(F)(F)F)cc(-c4ccc(C(F)(F)F)cc4)n3)cn2)c1
Solvent: ClCCl
Solvent: O=C(O)C(F)(F)F
Product: NS(=O)(=O)c1cccc(-c2cn(-c3cc(C(F)(F)F)cc(-c4ccc(C(F)(F)F)cc4)n3)cn2)c1
Temperature: 25 °C
Reaction time: 15 h
Yield: 94.5 %

Procedure:
To a cooled and stirred solution of N-tert-butyl-3-{1-[4-trifluoromethyl-6-(4-trifluoromethyl-phenyl)-pyridin-2-yl]-1H-imidazol-4-yl}-benzenesulfonamide (example 280) (0.110 g, 0.19 mmol) in dichloromethane (3 mL) was added TFA (3 mL) and the reaction mixture was allowed to stir at room temperature for 15 h. The mixture was evaporated to dryness and saturated NaHCO3 solution (5 mL), diethyl ether and heptane were added. The mixture was stirred at room temperature for 1 h, the precipitate was collected by filtration, washed with water and heptane/diethyl ether and dried to yield the title compound as a white solid (0.092 g, 93%). MS (ISP) 513.4 [(M+H)+]; mp>266° C.
Reaction SMILES: Cl[C:2]1[CH:25]=[CH:24][C:5]([O:6][C:7]2[CH:16]=[CH:15][CH:14]=[C:13]3[C:8]=2[CH:9]=[C:10]([C:21]([OH:23])=[O:22])[C@@H:11]([C:17]([F:20])([F:19])[F:18])[O:12]3)=[C:4](C)[CH:3]=1.[OH-].[Na+:28]>C(O)C>[O:6]([C:7]1[CH:16]=[CH:15][CH:14]=[C:13]2[C:8]=1[CH:9]=[C:10]([C:21]([O-:23])=[O:22])[C@@H:11]([C:17]([F:20])([F:18])[F:19])[O:12]2)[C:5]1[CH:24]=[CH:25][CH:2]=[CH:3][CH:4]=1.[Na+:28]
Reactant: Cc1cc(Cl)ccc1Oc1cccc2c1C=C(C(=O)O)[C@@H](C(F)(F)F)O2
Agent: [Na+]
Agent: [OH-]
Solvent: CCO
Product: O=C([O-])C1=Cc2c(Oc3ccccc3)cccc2O[C@@H]1C(F)(F)F

Procedure:
A solution of 36.4 mg (0.108 mmole) of (2S)-(+)-5-(4-chloro-2-methylphenoxy)-2-(trifluoromethyl)-2H-chromene-3-carboxylic acid in 1.5 mL of ethanol was treated with 1.07 mL of 0.1008N NaOH. The resultant mixture was lyophilized to provide 40.8 mg (quant.) of an off-white solid: MS (ES+) 337 (M+1, 100); 1H NMR (CD3OD/400 MHz) 5.84 (q, 1H, J=7.3 Hz), 6.43 (d, 1H, J=8.2 Hz), 6.70 (d, 1H, J=8.2 Hz), 6.99 (d, 2H, J=7.7 Hz), 7.12 (t, 1H, J=7.4 Hz), 7.17 (t, 1H, J=8.2 Hz), 7.35 (t, 2H, J−8.0 Hz), 8.55 (s, 1H); 19F NMR (CD3OD/400 MHz) 80.0 (d, 3F, J=7.7 Hz).
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[C:4]([CH:31]=[CH:32][CH:33]=1)[CH2:5][CH2:6][NH:7][C:8]1[N:13]=[C:12]([NH:14][C@H:15]2[CH2:18][C@@H:17]([NH:19]C(=O)OC(C)(C)C)[C:16]2([CH3:28])[CH3:27])[C:11]([C:29]#[N:30])=[CH:10][N:9]=1.FC(F)(F)C(O)=O>C(Cl)Cl>[NH2:19][C@H:17]1[CH2:18][C@@H:15]([NH:14][C:12]2[C:11]([C:29]#[N:30])=[CH:10][N:9]=[C:8]([NH:7][CH2:6][CH2:5][C:4]3[CH:31]=[CH:32][CH:33]=[C:2]([Cl:1])[CH:3]=3)[N:13]=2)[C:16]1([CH3:28])[CH3:27]
Reactant: CC(C)(C)OC(=O)N[C@@H]1C[C@H](Nc2nc(NCCc3cccc(Cl)c3)ncc2C#N)C1(C)C
Solvent: O=C(O)C(F)(F)F
Solvent: ClCCl
Product: CC1(C)[C@@H](N)C[C@H]1Nc1nc(NCCc2cccc(Cl)c2)ncc1C#N
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 54.1 %

Procedure:
To a solution of tert-butyl ((1R,3S)-3-((2-((3-chlorophenethyl)amino)-5-cyanopyrimidin-4-yl)amino)-2,2-dimethylcyclobutyl)carbamate (82 mg, 0.17 mmol) in dry DCM (2 mL) was added trifluoroacetic acid (1.5 mL) dropwise under cooling in an ice-water bath. The resulting mixture was stirred at room temperature for 30 min. After removal of the organic solvent, the residue was neutralized with ammonia and extracted with DCM. The combined organic layers were dried over anhydrous sodium sulfate and concentrated to give the crude product, which was purified by standard methods to afford the title compound (34.3 mg, 0.092 mmol, 55% yield). 1H NMR (400 MHz, CD3OD) δ (ppm) 8.04 (s, 1H), 7.27-7.14 (m, 4H), 4.16-3.97 (m, 1H), 3.74-3.49 (m, 2H), 2.90-2.85 (m, 3H), 2.60-2.49 (m, 1H), 1.92-1.86 (m, 1H), 1.22 (s, 3H), 0.92 (s 3H). MS (ESI) m/z 371.2 [M+H]+.
Reaction SMILES: [CH:1]1[CH:6]=[C:5]2[C:7]([N:9]([CH2:12][C:13]([OH:15])=O)[C:10](=[O:11])[C:4]2=[CH:3][CH:2]=1)=[O:8].C(Cl)(=O)C(Cl)=O.[CH2:22]([NH2:29])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1>ClCCl.CN(C=O)C.C(N(CC)CC)C.CO>[CH2:22]([NH:29][C:13](=[O:15])[CH2:12][N:9]1[C:10](=[O:11])[C:4]2[C:5](=[CH:6][CH:1]=[CH:2][CH:3]=2)[C:7]1=[O:8])[C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=1
Reactant: O=C(O)CN1C(=O)c2ccccc2C1=O
Reactant: NCc1ccccc1
Agent: O=C(Cl)C(=O)Cl
Solvent: ClCCl
Solvent: CCN(CC)CC
Solvent: CO
Product: O=C(CN1C(=O)c2ccccc2C1=O)NCc1ccccc1
Temperature: 25 °C
Reaction time: 4 h

Procedure:
To a stirred solution of N-phthaloylglycine (11.92 g, 58 mmol) in dichloromethane (200 mL) at room temperature, oxalyl chloride (7.5 mL, 87 mmol) was added. To the reaction mixture was then added DMF (two drops). The reaction mixture was concentrated after stirring four hours at room temperature. Dichloromethane (100 mL, dry) was added; then benzylamine (9.5 mL, 87 mmol) was added slowly into the solution, followed by addition of triethylamine (12 mL, 87 mmol), slowly into the solution. Dichloromethane (200 mL) and methanol (50 mL) were then added, 30 min. after the completed addition of triethylamine. The reaction mixture was extracted with 2N HCl solution twice, 1N NaOH solution one time, and 1N HCl one time, then dried over MgSO4. The solution was filtered and concentrated to yield N-benzyl-2-(1,3-dioxo-1,3-dihydro-isoindol-2-yl)-acetamide as a white solid.
Reaction SMILES: [OH:1][CH:2]([C:4]1[N:8]=[C:7]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[O:6][N:5]=1)[CH3:3].CC(OI1(OC(C)=O)(OC(C)=O)OC(=O)C2C=CC=CC1=2)=O>C(Cl)Cl>[C:2]([C:4]1[N:8]=[C:7]([C:9]([O:11][CH2:12][CH3:13])=[O:10])[O:6][N:5]=1)(=[O:1])[CH3:3]
Reactant: CCOC(=O)c1nc(C(C)O)no1
Agent: CC(=O)OI1(OC(C)=O)(OC(C)=O)OC(=O)c2ccccc21
Solvent: ClCCl
Product: CCOC(=O)c1nc(C(C)=O)no1
Temperature: 25 °C
Reaction time: 16 h

Procedure:
Into a flask containing ethyl 3-(1-hydroxyethyl)-1,2,4-oxadiazole-5-carboxylate (53.7 mmol, 10 g) in DCM (100 ml), Dess-Martin periodinane (80 mmol, 34.2 g) was added at 0° C. in portions and the resulting mixture was stirred at RT for 16 h. The reaction mixture was quenched with aqueous NaHCO3 solution and extracted with DCM. The organic layers were dried, filtered and evaporated. The product was purified by flash-chromatography. Yield 9.12 g. 1H-NMR (400 MHz; CDCl3): δ 1.47 (t, 3H), 2.76 (s, 3H), 4.58 (q, 2H).
Reaction SMILES: [CH3:1][O:2][C:3]([C:5]1([OH:18])[C:17]2[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=2[C:11]2[C:6]1=[CH:7][CH:8]=[CH:9][CH:10]=2)=[O:4].[CH3:19][N:20]1[CH2:24]C[C@@H:22](O)[CH2:21]1>C1(C)C=CC=CC=1>[CH3:19][N:20]1[CH2:21][CH2:22][C@@H:1]([O:2][C:3]([C:5]2([OH:18])[C:17]3[CH:16]=[CH:15][CH:14]=[CH:13][C:12]=3[C:11]3[C:6]2=[CH:7][CH:8]=[CH:9][CH:10]=3)=[O:4])[CH2:24]1
Reactant: COC(=O)C1(O)c2ccccc2-c2ccccc21
Reactant: CN1CC[C@@H](O)C1
Solvent: Cc1ccccc1
Product: CN1CC[C@@H](OC(=O)C2(O)c3ccccc3-c3ccccc32)C1
Yield: 30.7 %

Procedure:
0.980 g (0.0041 mol) of 9-Hydroxy-9H-fluorene-9-carboxylic acid methyl ester were dissolved in 30 ml of toluene. To this solution 0.412 g (0.0041 mol) of (3R)-1-methylpyrrolidin-3-ol (Intermediate I-19) and a catalitic amount of Na(0) were added and the mixture was refluxed using a Dean-Stark system for 24 hours. The reaction mixture was cooled, and extracted with HCl 2N. The aqueous layer was basified with K2CO3 and extracted with AcOEt (3×100 ml). The organic layers were combined, dried over Na2SO4 and evaporated to dryness to yield a residue which was purified by chromatography on silica gel eluting with chloroform plus isopropanol (0%→20%). Appropiate fractions were combined and evaporated to give 0.390 g (31%) of the title compound as an oil.
Reaction SMILES: [Cl:1][C:2]1[C:3]([C:9]2[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=2[C:16]([F:19])([F:18])[F:17])=[CH:4][C:5](=[O:8])[NH:6][CH:7]=1.Br[CH:21]([CH3:29])[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23]>>[Cl:1][C:2]1[C:3]([C:9]2[CH:14]=[C:13]([Cl:15])[CH:12]=[CH:11][C:10]=2[C:16]([F:17])([F:18])[F:19])=[CH:4][C:5](=[O:8])[N:6]([CH:21]([CH3:29])[C:22]([O:24][C:25]([CH3:28])([CH3:27])[CH3:26])=[O:23])[CH:7]=1
Reactant: CC(Br)C(=O)OC(C)(C)C
Reactant: O=c1cc(-c2cc(Cl)ccc2C(F)(F)F)c(Cl)c[nH]1
Product: CC(C(=O)OC(C)(C)C)n1cc(Cl)c(-c2cc(Cl)ccc2C(F)(F)F)cc1=O

Procedure:
123 mg (0.4 mmol) of 5-chloro-4-[5-chloro-2-(trifluoromethyl)phenyl]pyridin-2(1H)-one and 1.05 eq. of tert-butyl 2-bromopropanoate (racemate) were reacted according to General Method 4B at 100° C. Yield: 81 mg (47% of theory)
Reaction SMILES: [C:1](=[S:20])([S-:19])[S:2][CH2:3][CH2:4][NH:5][C:6]([O:8][CH2:9][C:10]1[CH:15]=[CH:14][C:13]([N+:16]([O-:18])=[O:17])=[CH:12][CH:11]=1)=[O:7].[K+].C(O[C@@H:26]1[NH:29][C:28](=[O:30])[C@H:27]1[O:31][CH3:32])(=O)C.O1CCOCC1>O.P([O-])([O-])([O-])=O>[N+:16]([C:13]1[CH:14]=[CH:15][C:10]([CH2:9][O:8][C:6]([NH:5][CH2:4][CH2:3][S:2][C:1]([S:19][C@H:26]2[NH:29][C:28](=[O:30])[C@@H:27]2[O:31][CH3:32])=[S:20])=[O:7])=[CH:11][CH:12]=1)([O-:18])=[O:17]
Reactant: O=C(NCCSC(=S)[S-])OCc1ccc([N+](=O)[O-])cc1
Reactant: CO[C@@H]1C(=O)N[C@H]1OC(C)=O
Agent: O=P([O-])([O-])[O-]
Agent: [K+]
Solvent: O
Solvent: C1COCCO1
Product: CO[C@H]1C(=O)N[C@@H]1SC(=S)SCCNC(=O)OCc1ccc([N+](=O)[O-])cc1
Reaction time: 0.5 h

Procedure:
A solution of 422 mg of potassium 2-p-nitrobenzyloxycarbonylaminoethyl trithiocarbonate in 1 ml of water is added dropwise at room temperature under, a nitrogen atmosphere to a solution of 159 mg (1 mmole) of (3S,4S)-4-acetoxy-3-methoxy-2-oxoazetidine in 3 ml of phosphate buffer of a pH of 7 and 0.2 ml of dioxan, and the mixture is stirred at the same temperature for 30 minutes. The reaction mixture is exhaustively extracted with methylene chloride. The combined organic phases are dried over sodium sulphate and concentrated by evaporation in vacuo. The residue is chromatographed over silica gel and yields the title compound with the following
Reaction SMILES: O1CCOCC1.Br[C:8]1[CH:13]=[CH:12][C:11]([N+:14]([O-:16])=[O:15])=[CH:10][N:9]=1.[C:17]([C:19]1[CH:28]=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][CH:20]=1)#[CH:18].C(NC(C)C)(C)C>[Cu]I.CC(C)([P](C(C)(C)C)([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)C(C)(C)C)C.C(OCC)(=O)C>[N+:14]([C:11]1[CH:12]=[CH:13][C:8]([C:18]#[C:17][C:19]2[CH:28]=[CH:27][C:22]([C:23]([O:25][CH3:26])=[O:24])=[CH:21][CH:20]=2)=[N:9][CH:10]=1)([O-:16])=[O:15]
Reactant: C#Cc1ccc(C(=O)OC)cc1
Reactant: O=[N+]([O-])c1ccc(Br)nc1
Agent: CC(C)(C)[P]([Pd][P](C(C)(C)C)(C(C)(C)C)C(C)(C)C)(C(C)(C)C)C(C)(C)C
Agent: [Cu]I
Solvent: CC(C)NC(C)C
Solvent: CCOC(C)=O
Solvent: C1COCCO1
Product: COC(=O)c1ccc(C#Cc2ccc([N+](=O)[O-])cn2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 88.1 %

Procedure:
To 20 mL of a dioxane solution including 2.0 g of 2-bromo-5-nitropyridine were added 1.58 g of methyl 4-ethynylbenzoate, 4.1 mL of N-isopropylpropan-2-amine and 281 mg of copper (I) iodide, and 504 mg of bis(tri-tert-butylphosphine)palladium(0) was further added thereto in an argon atmosphere, followed by stirring for 1 hour at room temperature. 50 ml of ethyl acetate was added to the reaction mixture, the precipitated insoluble material was collected by filtration, thereby obtaining 2.45 g of methyl 4-[(5-nitropyridin-2-yl)ethynyl]benzoate.
Reaction SMILES: C([O:3][C:4]([C:6]1[N:7]([CH2:17][CH3:18])[C:8]2[C:13]([CH:14]=1)=[C:12]([Cl:15])[C:11]([Cl:16])=[CH:10][CH:9]=2)=[O:5])C.[OH-].[Na+]>CO.CCOC(C)=O>[Cl:15][C:12]1[C:11]([Cl:16])=[CH:10][CH:9]=[C:8]2[C:13]=1[CH:14]=[C:6]([C:4]([OH:5])=[O:3])[N:7]2[CH2:17][CH3:18]
Reactant: CCOC(=O)c1cc2c(Cl)c(Cl)ccc2n1CC
Agent: [Na+]
Agent: [OH-]
Solvent: CCOC(C)=O
Solvent: CO
Product: CCn1c(C(=O)O)cc2c(Cl)c(Cl)ccc21
Temperature: 120 °C
Yield: 83 %

Procedure:
To a mixture of 4,5-dichloro-1H-indole-2-carboxylic acid ethyl ester (207 mg, 0.80 mmol) in DMF (2 mL) was added drop wise a suspension of NaH (41.2 mg, 60% dispersion in mineral oil, 1.03 mmol) in DMF (5 mL). The reaction mixture was stirred for 30 min, then ethyl iodide (156 mg, 1.0 mmol) diluted in 1 mL of DMF was added drop wise at room temperature and the mixture was stirred for an additional 1 hr. The reaction mixture was diluted with 100 mL of EtOAc and washed with saturated ammonium chloride (100 mL) and brine (50 mL). The organic layer was dried over anhydrous sodium sulfate and the solvent was removed. The residue was purified on a flash chromatography column with EtOAc/hexanes to afford 4,5-dichloro-1-ethyl-1H-indole-2-carboxylic acid ethyl ester (160 mg, 70% yield). The 4,5-dichloro-1-ethyl-1H-indole-2-carboxylic acid ethyl ester (160 mg, 0.56 mmol) was diluted in 10 mL of methanol and 4 mL of 1N NaOH and placed in a sealed tube. The reaction mixture was heated under microwave condition at 120° C. for 25 min. The reaction mixture was diluted with 150 mL of EtOAc and washed with 100 mL of 1N HCl, brine (50 L) and dried. The solvent was removed to afford the product 4,5-dichloro-1-ethyl-1H-indole-2-carboxylic acid (120 mg, 84% yield) as a white solid. LCMS for C11H9Cl2NO2 calcd. (m/e) 257, observed 256 (M−H).
Reaction SMILES: Cl.[NH2:2][CH2:3][C:4]1[CH:5]=[C:6]([OH:14])[C:7](=[CH:12][CH:13]=1)[C:8]([O:10][CH3:11])=[O:9].C(N(CC)C(C)C)(C)C.[CH2:24]([O:31][C:32](ON1C(=O)CCC1=O)=[O:33])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1>C(Cl)(Cl)Cl>[CH2:24]([O:31][C:32]([NH:2][CH2:3][C:4]1[CH:5]=[C:6]([OH:14])[C:7](=[CH:12][CH:13]=1)[C:8]([O:10][CH3:11])=[O:9])=[O:33])[C:25]1[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=1
Reactant: O=C(OCc1ccccc1)ON1C(=O)CCC1=O
Reactant: COC(=O)c1ccc(CN)cc1O
Agent: Cl
Solvent: ClC(Cl)Cl
Solvent: CCN(C(C)C)C(C)C
Product: COC(=O)c1ccc(CNC(=O)OCc2ccccc2)cc1O
Temperature: 25 °C
Reaction time: 4 h
Yield: 84.3 %

Procedure:
Methyl 4-aminomethylsalicylate hydrochloride (5.04 g, 23.2 mmoles) was suspended in chloroform (80 mL) and N,N-diisopropylethylamine (4.10 mL, 23.5 mmoles) and N-(benzyl-oxycarbonyloxy)succinimide (6.48 g, 26.0 mmoles) were added. The reaction mixture was stirred at room temperature for 4 hours, during which time all solids dissolved. The reaction mixture was then extracted with 1N aqueous hydrochloric acid (100 mL), water (75 mL), and saturated aqueous sodium chloride (50 mL). The chloroform solution was dried over anhydrous magnesium sulfate, filtered and evaporated to dryness to give a white solid. The product was crystallized from ethyl acetate:hexanes to afford 6.17 g (84% yield) of methyl N-(benzyloxy-carbonyl)-4-aminomethylsalicylate (m.p. 91°-92°C., open capillary, uncorrected).
Reaction SMILES: Cl[C:2]1[C:11]2[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=2[C:5]2=[N:12][CH:13]=[CH:14][N:4]2[N:3]=1.[NH:15]1[CH2:19][CH2:18][CH2:17][CH2:16]1>>[N:15]1([C:2]2[C:11]3[CH2:10][CH2:9][CH2:8][CH2:7][C:6]=3[C:5]3=[N:12][CH:13]=[CH:14][N:4]3[N:3]=2)[CH2:19][CH2:18][CH2:17][CH2:16]1
Reactant: C1CCNC1
Reactant: Clc1nn2ccnc2c2c1CCCC2
Product: c1cn2nc(N3CCCC3)c3c(c2n1)CCCC3
Temperature: 0 °C

Procedure:
A mixture was prepared by adding 4.5 g of 6-chloro-7,8,9,10-tetrahydroimidazo[2,1-a]phthalazine to 8.7 g of pyrrolidine and this was heated at reflux for 6.5 hours during which time the mixture turned brown. The reaction mixture was then poured into about 150 ml of ice water. A solid formed immediately and this was separated by filtration and air dried to give 6-(1-pyrrolidinyl)-7,8,9,10-tetrahydroimidazo[2,1-a]phthalazine melting at about 128° C.
Reaction SMILES: [OH-].[Na+].[CH3:3][O:4][C:5]1[CH:6]=[C:7]([CH:10]=[CH:11][C:12]=1[C:13](N(C)C)=O)[CH:8]=[S:9].BrC[C:20]([O:22][CH2:23][CH3:24])=[O:21].Cl>O.C(O)C>[CH3:3][O:4][C:5]1[CH:6]=[C:7]([CH:10]=[CH:11][C:12]=1[CH2:13][C:20]([O:22][CH2:23][CH3:24])=[O:21])[CH:8]=[S:9]
Reactant: COc1cc(C=S)ccc1C(=O)N(C)C
Reactant: CCOC(=O)CBr
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: O
Solvent: CCO
Product: CCOC(=O)Cc1ccc(C=S)cc1OC
Temperature: 25 °C
Reaction time: 3 h

Procedure:
A solution of sodium hydroxide (4.92 g) in water (5 ml) is diluted with ethanol (80 ml), and the mixture is subjected to deaeration, and then put under nitrogen atmosphere. To the mixture is added 3-methoxy-4-dimethylaminocarbonylthiobenzaldehyde (20 g), and the mixture is refluxed for 14 hours. After cooling, to the mixture is added dropwise ethyl bromoacetate (9.74 ml), and the mixture is stirred at room temperature for three hours. To the mixture are added ethanol, 1.5N hydrochloric acid and water, and the mixture is extracted with chloroform. The extract is dried over sodium sulfate and concentrated, and the residue is purified by silica gel column chromatography (solvent; n-hexane:ethyl acetate=9:1→5.6:1→4:1) to give 3-methoxy-4-ethoxycarbonylmethylthiobenzaldehyde (11.8 g) as white solid.
Reaction SMILES: [Na].[N+:2]([C:5]1[CH:6]=[C:7]2[C:11](=[CH:12][CH:13]=1)[NH:10][CH:9]=[CH:8]2)([O-:4])=[O:3].[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][C:24](=O)[CH2:23][CH2:22]1)=[O:20])([CH3:17])([CH3:16])[CH3:15]>CO>[C:14]([O:18][C:19]([N:21]1[CH2:26][CH2:25][C:24]([C:8]2[C:7]3[C:11](=[CH:12][CH:13]=[C:5]([N+:2]([O-:4])=[O:3])[CH:6]=3)[NH:10][CH:9]=2)=[CH:23][CH2:22]1)=[O:20])([CH3:17])([CH3:15])[CH3:16]
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Reactant: O=[N+]([O-])c1ccc2[nH]ccc2c1
Agent: [Na]
Solvent: CO
Product: CC(C)(C)OC(=O)N1CC=C(c2c[nH]c3ccc([N+](=O)[O-])cc23)CC1
Temperature: 65 °C
Yield: 72 %

Procedure:
To a stirred solution of sodium (2.51 g, 105 mmol, 7 eq) in absolute methanol (50 mL) was added 5-nitroindole (2.43 g, 15.0 mmol) and N-t-butoxycarbonyl4-piperidone (8.96 g, 45.0 mmol, 3.0 eq). The resulting reaction solution was heated at reflux (65° C.) under nitrogen for 24 hours. The resulting reaction solution was evaporated under reduced pressure, and the residue was partitioned between a saturated solution of sodium hydrogen carbonate (50 mL) and ethyl acetate (50 mL). The organic layer was removed, and the aqueous layer was extracted with ethyl acetate (2×50 mL). The organic extracts were combined, dried (MgSO4), and evaporated under reduced pressure. Column chromatography of the extraction residue using silica gel (approximately 100 g) and elution with ethyl acetate in hexanes [1:2 to 1:1 gradient] afforded the title compound (72%) as yellow solid: mp, decomposes 230° C.; 1H NMR (CDCl3) δ 9.24 (br s, 1H), 8.78 (d, J=1.3 Hz, 1H), 8.09 (dd, J=1.4 and 9.4 Hz, 1H), 7.40 (d, J=9.3 Hz, 1H), 7.30 (d, J=1.8 Hz, 1H), 6.17-6.15 (m, 1H), 4.16-4.13 (m, 2H), 3.68 (t, J=5.8 Hz, 2H), 2.58-2.48 (m, 2H), 1.50 (s, 9H); Anal. calcd for C15H21N3O4.0.1 H2O: C, 62.63; H, 6.19; N, 12.17. Found: C, 62.71; H, 6.09; N, 11.81.
Reaction SMILES: Cl.[C:2]([C:5]1[O:6]C(=O)[C:8](=[O:10])[N:9]=1)([CH3:4])=[CH2:3].[C:12]([O:17][CH3:18])(=[O:16])[C:13]([CH3:15])=[CH2:14].[C:19]([O:23][CH2:24][CH2:25][CH2:26][CH3:27])(=[O:22])[CH:20]=[CH2:21].N(C(C)(CC(C)C)C#N)=NC(C)(CC(C)C)C#N>C1(C)C=CC=CC=1.C(OCC)(=O)C>[C:5]([N:9]=[C:8]=[O:10])(=[O:6])[C:2]([CH3:4])=[CH2:3].[C:12]([O:17][CH3:18])(=[O:16])[C:13]([CH3:15])=[CH2:14].[C:19]([O:23][CH2:24][CH2:25][CH2:26][CH3:27])(=[O:22])[CH:20]=[CH2:21]
Reactant: C=C(C)C1=NC(=O)C(=O)O1
Agent: C=C(C)C(=O)OC
Agent: C=CC(=O)OCCCC
Agent: CC(C)CC(C)(C#N)N=NC(C)(C#N)CC(C)C
Solvent: Cc1ccccc1
Solvent: CCOC(C)=O
Product: C=C(C)C(=O)N=C=O
Temperature: 100 °C
Reaction time: 5 h

Procedure:
A mixture of 2-isopropenyloxazoline-4,5-dione hydrochloride (15 g), methyl methacrylate (20 g), n-butyl acrylate (15 g), 2,2'-azobis(2,4-dimethylvaleronitrile) (1.25 g) and ethyl acetate (25 g) was dropwise added to toluene (50 g) heated at 100° C. in 90 minutes while stirring. Stirring was further continued for 5 hours, whereby a copolymer of methacryloyl isocyanate with methyl methacrylate and n-butyl acrylate was produced. Viscosity, C-D (determined by Gardner bubble viscometer). Non-volatile content, 40%. Mw, 7100 (determined by gel permeation chromatography).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[CH2:13][C:12]([NH:14][NH:15]S(C2C=CC(C)=CC=2)(=O)=O)=[CH:11][C:10](=[O:26])[CH2:9]1.C(=O)([O-])[O-].[K+].[K+].Br[CH2:34][C:35]([C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1)=O>CO>[Cl:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[CH:8]1[CH2:13][C:12]2[N:14]=[N:15][CH:34]=[C:35]([C:37]3[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=3)[C:11]=2[C:10](=[O:26])[CH2:9]1
Reactant: Cc1ccc(S(=O)(=O)NNC2=CC(=O)CC(c3ccccc3Cl)C2)cc1
Reactant: O=C(CBr)c1ccccc1
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CO
Product: O=C1CC(c2ccccc2Cl)Cc2nncc(-c3ccccc3)c21
Temperature: 80 °C
Reaction time: 3 h
Yield: 39.8 %

Procedure:
A mixture of 5-(2-chlorophenyl)-1-[2-(4-methylphenylsulfonyl)hydrazino]cyclohexen-3-one (1.35 g), anhydrous potassium carbonate (1.19 g), 2-bromoacetophenone (0.893 g) and methanol (30 ml) was stirred at 80° C. for 3 hours. Under reduced pressure, the solvent was evaporated, and the residue was extracted with ethyl acetate. The organic layer was concentrated, and the residue was purified with silica gel column chromatography to give 7-(2-chlorophenyl)-4-phenyl-5,6,7,8-tetrahydrocinnolin-5-one (0.46 g) as oil.
Reaction SMILES: C(=O)([O-])[O-].[K+].[K+].[I:7][C:8]1[CH:13]=[CH:12][C:11]([OH:14])=[CH:10][CH:9]=1.[C:15]([O:19][C:20]([N:22]1[CH2:27][CH2:26][CH:25](OS(C)(=O)=O)[CH2:24][CH2:23]1)=[O:21])([CH3:18])([CH3:17])[CH3:16].[OH-].[Na+]>CN(C)C=O>[I:7][C:8]1[CH:13]=[CH:12][C:11]([O:14][CH:25]2[CH2:26][CH2:27][N:22]([C:20]([O:19][C:15]([CH3:18])([CH3:17])[CH3:16])=[O:21])[CH2:23][CH2:24]2)=[CH:10][CH:9]=1
Reactant: CC(C)(C)OC(=O)N1CCC(OS(C)(=O)=O)CC1
Reactant: Oc1ccc(I)cc1
Agent: O=C([O-])[O-]
Agent: [K+]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CC(C)(C)OC(=O)N1CCC(Oc2ccc(I)cc2)CC1
Temperature: 80 °C
Reaction time: 24 h

Procedure:
Potassium carbonate (15 g, 109 mmol) was added to a dimethylformamide (200 mL) solution of 4-iodophenol (8.0 g, 36.4 mmol) and 1-t-butoxycarbonyl-4-methanesulfonyloxypiperidine (13.2 g, 47.3 mmol), and stirred at 80° C. for 24 hours. The reaction mixture was cooled to room temperature, then aqueous 2 N sodium hydroxide solution was added to the reaction mixture, and extracted with diethyl ether. The organic layer was washed with saturated brine, dried with anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified through silica gel column chromatography (C-300, hexane/ethyl acetate=4/1) to obtain the entitled compound (12 g, 82
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8][CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:26]=[CH:25][C:17]3[C:18]([CH3:24])([CH3:23])[O:19][C:20](=[O:22])[NH:21][C:16]=3[CH:15]=2)=[CH:4][CH:3]=1.[OH:27]O>>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([CH2:9][CH2:10][CH2:11][CH2:12][O:13][C:14]2[CH:26]=[CH:25][C:17]3[C:18]([CH3:23])([CH3:24])[O:19][C:20](=[O:22])[NH:21][C:16]=3[CH:15]=2)=[O:27])=[CH:4][CH:3]=1
Reactant: OO
Reactant: CC1(C)OC(=O)Nc2cc(OCCCCSc3ccc(Cl)cc3)ccc21
Product: CC1(C)OC(=O)Nc2cc(OCCCCS(=O)c3ccc(Cl)cc3)ccc21

Procedure:
Prepared analogously to Example 2 from 7-[4-(4-chlorophenylmercapto)-butoxy]-4,4-dimethyl-4H-3,1-benzoxazin-2-one and hydrogen peroxide.