Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: F[C:2]1[C:3]([N+:15]([O-:17])=[O:16])=[C:4]2[C:9](=[CH:10][C:11]=1[F:12])[NH:8][C:7](=[O:13])[C:6](=[O:14])[NH:5]2.[O-:18][CH2:19][CH3:20].[Na+].Cl>O>[F:12][C:11]1[CH:10]=[C:9]2[C:4]([NH:5][C:6](=[O:14])[C:7](=[O:13])[NH:8]2)=[C:3]([N+:15]([O-:17])=[O:16])[C:2]=1[O:18][CH2:19][CH3:20]
Reactant: CC[O-]
Reactant: O=c1[nH]c2cc(F)c(F)c([N+](=O)[O-])c2[nH]c1=O
Agent: Cl
Agent: [Na+]
Solvent: O
Product: CCOc1c(F)cc2[nH]c(=O)c(=O)[nH]c2c1[N+](=O)[O-]
Yield: 91 %

Procedure:
A solution of 24 mg (0.098 mmol) of 6,7-difluoro-5-nitro-1,4-dihydroquinoxaline-2,3-dione and 24 mg (0.33 mmol) of sodium ethoxide (96%) in 0.5 mL of DMSO-d6 was kept at room temperature for 5 h. The red solution was added to 3 mL of water and acidified with 2 N HCl to pH=4. The precipitate was filtered, washed with water, and dried to leave a yellow solid (24 mg, 91%); mp 293-295° C.; 1H NMR (DMSO-d6), 1.239 (t, 3, J=7.0), 4.141 (q, 2, J=7.2), 7.152 (1, d, J=11.7), 11.975 (s, 1), 12.135 (s, 1). 19F NMR, -134.06 (mb). MS, 269 (M+, 90), 241 (100), 195 (70). HRMS, Calcd for C10H8FN3O5 269.0443, found 269.0454.
Reaction SMILES: N[C:2]1[C:3]([CH2:9][CH2:10][CH2:11][C:12]#[N:13])=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1.N([O-])=[O:15].[Na+].[OH-].[Na+]>S(=O)(=O)(O)O>[OH:15][C:2]1[C:3]([CH2:9][CH2:10][CH2:11][C:12]#[N:13])=[N:4][CH:5]=[C:6]([CH3:8])[CH:7]=1
Reactant: O=N[O-]
Reactant: Cc1cnc(CCCC#N)c(N)c1
Agent: O=S(=O)(O)O
Agent: [Na+]
Agent: [OH-]
Product: Cc1cnc(CCCC#N)c(O)c1
Yield: 50.7 %

Procedure:
A solution of 3-amino-2-(3-cyanopropyl)-5-methylpyridine [from Example 1(c)] (1 g) in diluted sulphuric acid (0.78 ml conc. and 6.5 ml water) was reacted with sodium nitrite (0.59 g in 3 ml water) between 6°-10° C. The pH was brought to 6.5 with sodium hydroxide and the product was extracted with chloroform, chromatographed on silica in chloroform-methanol giving 3-hydroxy-2-(3-cyanopropyl)-5-methylpyridine (0.51 g) m.p. 132.5° C.
Reaction SMILES: [OH:1][CH:2]([CH2:16][OH:17])[CH2:3][N:4]=[C:5]=[C:6]1[S:10][C:9]([C:11]2[S:12][CH:13]=[CH:14][CH:15]=2)=[CH:8][CH2:7]1.[BH4-].[Na+]>CO>[OH:1][CH:2]([CH2:16][OH:17])[CH2:3][NH:4][CH2:5][C:6]1[S:10][C:9]([C:11]2[S:12][CH:13]=[CH:14][CH:15]=2)=[CH:8][CH:7]=1
Reactant: OCC(O)CN=C=C1CC=C(c2cccs2)S1
Agent: [BH4-]
Agent: [Na+]
Solvent: CO
Product: OCC(O)CNCc1ccc(-c2cccs2)s1

Procedure:
5-(N-2,3-dihydroxypropyliminomethylidene)-2,2'-bithiophene was dissolved in 50 ml of methanol and stirred in ice bath. NaBH4 was added until bubbling stopped. After the methanol was removed under reduced pressure and the residue was extracted with dichloromethane. The extract was washed with saturated NaCl solution, dried over anhydrous magnesium sulfate and condensed under reduced pressure. The crude yellow glue-like product was thus obtained.
Reaction SMILES: C([Li])CCC.[Br-].[CH3:7][O:8][C:9]1[CH:10]=[C:11]([CH:14]=[C:15]([O:19][CH3:20])[C:16]=1[O:17][CH3:18])[CH2:12][PH3+].[CH2:21]([O:24][C:25]1[CH:32]=[CH:31][C:28]([CH:29]=O)=[C:27]([O:33][Si:34]([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35])[C:26]=1[O:41][Si:42]([C:45]([CH3:48])([CH3:47])[CH3:46])([CH3:44])[CH3:43])[CH:22]=[CH2:23].O>C1COCC1>[Si:34]([O:33][C:27]1[C:28](/[CH:29]=[CH:12]\[C:11]2[CH:10]=[C:9]([O:8][CH3:7])[C:16]([O:17][CH3:18])=[C:15]([O:19][CH3:20])[CH:14]=2)=[CH:31][CH:32]=[C:25]([O:24][CH2:21][CH:22]=[CH2:23])[C:26]=1[O:41][Si:42]([C:45]([CH3:48])([CH3:47])[CH3:46])([CH3:43])[CH3:44])([C:37]([CH3:40])([CH3:39])[CH3:38])([CH3:36])[CH3:35]
Reactant: COc1cc(C[PH3+])cc(OC)c1OC
Reactant: C=CCOc1ccc(C=O)c(O[Si](C)(C)C(C)(C)C)c1O[Si](C)(C)C(C)(C)C
Agent: [Br-]
Agent: [Li]CCCC
Solvent: O
Solvent: C1CCOC1
Product: C=CCOc1ccc(/C=C\c2cc(OC)c(OC)c(OC)c2)c(O[Si](C)(C)C(C)(C)C)c1O[Si](C)(C)C(C)(C)C
Temperature: -70 °C
Reaction time: 0.25 h
Yield: 58.9 %

Procedure:
n-Butyllithium (0.37 mL, 0.59 mmol, 1.6 M in hexanes) was added dropwise over 5 min to a solution of 3,4,5-trimethoxybenzylphosphonium bromide (0.27 g, 0.52 mmol) in THF (3 mL) at −10° C. The reaction mixture was stirred at this temperature for 15 min then cooled to −70° C. and a solution of 41 (0.10 g, 0.24 mmol) in THF (3 mL) was added and the reaction mixture was allowed to warm to rt with stirring overnight (16 h). The reaction mixture was cooled to 0° C. and water was added. The reaction mixture was extracted with t-BuOMe (3×) and the organic phase was washed successively with water and brine, dried (Na2SO4) and evaporated to dryness to give crude product (0.3 g). Purification by column chromatography (SiO2 2:98 EtOAc:cyclohexane) gave 42 (83 mg, 60%) as an 85:15 mixture of Z:E isomers.
Reaction SMILES: Cl[C:2]([O:4][C:5]1[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][CH:6]=1)=[O:3].[CH3:14][O:15][N:16]=[CH:17][C:18]1[CH2:19][NH:20][CH2:21][CH2:22][CH:23]=1.C(N(CC)CC)C>ClCCl>[CH3:14][O:15][N:16]=[CH:17][C:18]1[CH2:19][N:20]([C:2]([O:4][C:5]2[CH:10]=[CH:9][C:8]([N+:11]([O-:13])=[O:12])=[CH:7][CH:6]=2)=[O:3])[CH2:21][CH2:22][CH:23]=1
Reactant: O=C(Cl)Oc1ccc([N+](=O)[O-])cc1
Reactant: CON=CC1=CCCNC1
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CON=CC1=CCCN(C(=O)Oc2ccc([N+](=O)[O-])cc2)C1
Temperature: 25 °C
Reaction time: 0.33 h
Yield: 94.3 %

Procedure:
A solution of 97% 4-nitrophenyl chloroformate (1.5 g, 7.22 mmoles) in dichloromethane (15 mL) was added at 0° C. to a stirred solution of 1,2,5,6-tetrahydropyridine-3-carboxaldehyde-O-methyloxime (0.92 g, 6.6 mmoles) and triethylamine (0.92 mL, 6.6 mmoles) in dichloromethane (20 mL). The reaction mixture was then stirred at room temperature for 20 minutes, the solvent was evaporated and the residue was partitioned between water and ethyl acetate. The organic layer was dried (Na2SO4) and evaporated. The solid was recrystallized from benzene-cyclohexane to give 1.9 g (95%) of the desired product with mp 109°-110° C.
Reaction SMILES: O.O.O.C([O-])(=O)C.[Na+].Cl[CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12].[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH2:21])=[CH:19][CH:18]=1>C(O)C>[Cl:16][C:17]1[CH:23]=[CH:22][C:20]([NH:21][CH2:10][C:11]([O:13][CH2:14][CH3:15])=[O:12])=[CH:19][CH:18]=1
Reactant: CCOC(=O)CCl
Reactant: Nc1ccc(Cl)cc1
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: CCO
Product: CCOC(=O)CNc1ccc(Cl)cc1
Yield: 55.9 %

Procedure:
Sodium acetate trihydrate (6 g) was added to a solution of commercial ethyl chloroacetate (6.2 g) and commercial 4-chloroaniline (6.4 g) in ethanol (5 ml). The mixture was heated to reflux for 5 h. After cooling in an ice bath the product precipitates. The solid was collected by suction filtration and washed with water. The still wet product was recrystallised from ethanol to give ethyl N-(4-chlorophenyl)glycinate (5.99 g) as greyish crystals.
Reaction SMILES: Br[C:2]1[C:15]2[CH:14]=[CH:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1.C([Li:20])CCC>CCCCCCC>[Li:20][C:2]1[C:15]2[CH:14]=[CH:13][C:12]3[C:7](=[CH:8][CH:9]=[CH:10][CH:11]=3)[C:6]=2[CH:5]=[CH:4][CH:3]=1
Reactant: [Li]CCCC
Reactant: Brc1cccc2c1ccc1ccccc12
Solvent: CCCCCCC
Product: [Li]c1cccc2c1ccc1ccccc12

Procedure:
2.1 Grams (8.3 mmols) of a 1-bromophenanthrene was dissolved in 43 ml of heptane, 5.3 ml (1.6 mols/l, 8.5 mmols) of butyl lithium was added thereto at room temperature to obtain a 1-lithiophenanthrene, which was cooled down to −5° C., followed by the addition of 2.2 g (5.2 mmols) of the above DBBF. The mixture was stirred for one hour and to which was further added the THF at a temperature of not higher than 0° C. The mixture was stirred at this temperature for 2 hours. The conversion was 99%.
Reaction SMILES: [C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH:10]([NH:13][C:14]([C:16]2[S:17][CH:18]=[CH:19][C:20]=2[NH:21][C:22]2[CH:27]=[CH:26][N:25]=[C:24]3[NH:28][CH:29]=[CH:30][C:23]=23)=[O:15])[CH2:9]1)=[O:7])([CH3:4])([CH3:3])[CH3:2].[C:31](N1CCCC(N)C1)(OC(C)(C)C)=O>>[C:1]([O:5][C:6]([N:8]1[CH2:12][CH2:11][CH2:31][CH:10]([NH:13][C:14]([C:16]2[S:17][CH:18]=[CH:19][C:20]=2[NH:21][C:22]2[CH:27]=[CH:26][N:25]=[C:24]3[NH:28][CH:29]=[CH:30][C:23]=23)=[O:15])[CH2:9]1)=[O:7])([CH3:2])([CH3:4])[CH3:3]
Reactant: CC(C)(C)OC(=O)N1CCC(NC(=O)c2sccc2Nc2ccnc3[nH]ccc23)C1
Reactant: CC(C)(C)OC(=O)N1CCCC(N)C1
Product: CC(C)(C)OC(=O)N1CCCC(NC(=O)c2sccc2Nc2ccnc3[nH]ccc23)C1

Procedure:
This compound was prepared in an analogous manner as 3-{[3-(1H-Pyrrolo[2,3-b]pyridin-4-ylamino)-thiophene-2-carbonyl]-amino}-pyrrolidine-1-carboxylic acid tert-butyl ester using 1-BOC-3-aminopiperidine instead of 1-BOC-3-aminopyrrolidine. LCMS (ESI) 442 (M+H) 1H NMR (400 MHz, DMSO-d6) δ ppm 11.52 (1H, br. s.) 10.27 (1H, br. s.) 8.02 (1H, d, J=5.47 Hz) 7.87 (1H, d, J=8.20 Hz) 7.80 (1H, d, J=5.37 Hz) 7.47 (1H, d, J=5.47 Hz) 7.31 (1H, dd, J=3.32, 2.54 Hz) 6.80 (1H, d, J=5.47 Hz) 6.44 (1H, dd, J=3.42, 1.76 Hz) 3.79 (3H, dd, J=6.78, 3.17 Hz) 2.76 (1H, t, J=12.45 Hz) 1.83 (1H, dd, J=12.93, 3.27 Hz) 1.65 (1H, dd, J=8.69, 3.22 Hz) 1.52 (1H, dd, J=11.76, 3.95 Hz) 1.37 (9H, s)
Reaction SMILES: [CH3:1][C:2]1[C:7]([NH:8][CH2:9][CH2:10][CH3:11])=[C:6]([O:12][CH2:13][CH2:14][O:15][CH2:16][CH2:17][O:18][CH3:19])[CH:5]=[CH:4][CH:3]=1.[OH-].[Na+].[Cl:22][CH2:23][C:24](Cl)=[O:25]>C(Cl)Cl>[Cl:22][CH2:23][C:24]([N:8]([CH2:9][CH2:10][CH3:11])[C:7]1[C:2]([CH3:1])=[CH:3][CH:4]=[CH:5][C:6]=1[O:12][CH2:13][CH2:14][O:15][CH2:16][CH2:17][O:18][CH3:19])=[O:25]
Reactant: CCCNc1c(C)cccc1OCCOCCOC
Reactant: O=C(Cl)CCl
Agent: [Na+]
Agent: [OH-]
Solvent: ClCCl
Product: CCCN(C(=O)CCl)c1c(C)cccc1OCCOCCOC
Reaction time: 0.17 h
Yield: 39 %

Procedure:
A mixture containing a portion of the 6-methyl-2-[2-(2-methoxyethoxy)ethoxy]-N-2-methylethyl aniline (5.34 g; 0.02 mole) and sodium hydroxide (0.88 g; 0.22 mole) in 150 ml. of methylene chloride was cooled to 10° C. To the reaction mixture was added dropwise chloroacetyl chloride (2.5 g; 0.022 mole) and the resulting mixture was stirred for 10 minutes. The layers were separated and the organic methylene chloride layer was washed with water, dried over magnesium sulfate and concentrated in vacuo to yield a crude product. The crude product was separated on a silica gel column using a 2:5 ethyl acetate:cyclohexane mixture as the eluant to yield 2-chloro-N-2-methylethyl-N-[6-methyl-2-(2-(2-methoxyethoxy)ethoxy)phenyl]acetamide (Compound No. 102) (2.7 g; 39% yield) as a clear yellow oil having a boiling point of 163° C. (0.13 mmHg) and the following analysis:
Reaction SMILES: [F:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[CH:12][N:11]=[C:10]([CH3:14])[CH:9]=2)=[CH:4][CH:3]=1.ClC1C=CC=C(C(OO)=[O:23])C=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:8]2[CH:13]=[CH:12][N+:11]([O-:23])=[C:10]([CH3:14])[CH:9]=2)=[CH:6][CH:7]=1
Reactant: Cc1cc(-c2ccc(F)cc2)ccn1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])O
Agent: [Na+]
Solvent: ClCCl
Product: Cc1cc(-c2ccc(F)cc2)cc[n+]1[O-]
Temperature: 25 °C
Reaction time: 6 h
Yield: 203 %

Procedure:
To a solution of 1.50 g (8.0 mmol) of 4-(4-Fluoro-phenyl)-2-methyl-pyridine in 25 ml of methylene chloride were added 5.93 g (24 mmol, 3.0 equiv.) of 70% m-Chloroperbenzoic acid. The reaction was stirred for 6 h at room temperature. The reaction was worked up with 50 ml 5% sodium bicarbonate solution. The aqueous phase was extracted twice with 40 ml of methylene chloride. The combined organic phases were washed with 30 ml of brine, dried over magnesium sulfate, and concentrated in vaccuo to yield 3.3 g of a yellow oil which was purified by flash chromatography (ethyl acetate/methanol 9:1) to yield the title compound (1.31 g, 80%) as a crystalline light brown solid, MS (ISP): m/e=204.1 (M+H)+.
Reaction SMILES: [C:1]([CH:3]([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:4]([NH:6][NH2:7])=[O:5])#[N:2].[CH3:14][C:15](=O)[CH2:16][C:17](=O)[CH3:18]>>[CH3:14][C:15]1[CH:16]=[C:17]([CH3:18])[N:7]2[N:6]=[C:4]([OH:5])[C:3]([C:8]3[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=3)=[C:1]2[N:2]=1
Reactant: CC(=O)CC(C)=O
Reactant: N#CC(C(=O)NN)c1ccccc1
Product: Cc1cc(C)n2nc(O)c(-c3ccccc3)c2n1
Temperature: 60 °C
Reaction time: 3 h
Yield: 27.4 %

Procedure:
2-cyano-2-phenylacetohydrazide [Int-1A] (3.27 g, 18.3 mmol, 1.0 eq) and pentane-2,4-dione (1.89 mL, 18.3 mmol, 1.0 eq) were dissolved in 59 mL acidic acid and stirred for 3 h at 60° C. The resulting yellow suspension was cooled to rt and the precipitate was isolated by filtration. The solid was washed with hexane and dried to give 1.20 g (27% yield) of the title compound.
Reaction SMILES: Cl[C:2]1[N:7]=[CH:6][C:5]([C:8]2[NH:12][C:11]3[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=3[N:9]=2)=[CH:4][CH:3]=1.[NH:17]1[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1>CN1CCCC1=O>[N:17]1([C:2]2[N:7]=[CH:6][C:5]([C:8]3[NH:12][C:11]4[CH:13]=[CH:14][CH:15]=[CH:16][C:10]=4[N:9]=3)=[CH:4][CH:3]=2)[CH2:22][CH2:21][NH:20][CH2:19][CH2:18]1
Reactant: Clc1ccc(-c2nc3ccccc3[nH]2)cn1
Reactant: C1CNCCN1
Solvent: CN1CCCC1=O
Product: c1ccc2[nH]c(-c3ccc(N4CCNCC4)nc3)nc2c1
Temperature: 140 °C
Reaction time: 2 h
Yield: 93 %

Procedure:
A mixture of 2-(6-chloropyridin-3-yl)-1H-benzoimidazole (0.468 g, 2.040 mmol) and piperazine (0.516 g, 6.000 mmol) in 1-methyl-2-pyrrolidone was heated to 140° C. with stirring for 2 hours. The solvent was removed in vacuo. The residue was diluted with water (100 mL) and stirred for 15 minutes. A white precipitate was formed which was collected by filtration and dried to afford the title compound in 93% yield (0.529 g, 1.900 mmol).
Reaction SMILES: [OH:1][N:2]=[C:3]([C:19]1[CH:24]=[CH:23][C:22]([O:25][CH3:26])=[CH:21][CH:20]=1)[C:4]([C:11]1[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=1)=[CH:5][CH2:6][C:7]([O:9][CH3:10])=[O:8].BrN1C(=O)CCC1=O.C(OCC)(=O)C>C1C=CC=CC=1>[CH3:26][O:25][C:22]1[CH:21]=[CH:20][C:19]([C:3]2[C:4]([C:11]3[CH:16]=[CH:15][C:14]([O:17][CH3:18])=[CH:13][CH:12]=3)=[C:5]([CH2:6][C:7]([O:9][CH3:10])=[O:8])[O:1][N:2]=2)=[CH:24][CH:23]=1
Reactant: COC(=O)CC=C(C(=NO)c1ccc(OC)cc1)c1ccc(OC)cc1
Agent: O=C1CCC(=O)N1Br
Solvent: CCOC(C)=O
Solvent: c1ccccc1
Product: COC(=O)Cc1onc(-c2ccc(OC)cc2)c1-c1ccc(OC)cc1
Reaction time: 2 h

Procedure:
In 50 g of benzene was dissolved 3.05 g of methyl 5-hydroxyimino-4,5-bis(4-methoxyphenyl-3-pentenoate obtained in Example 3. Thereto was added gradually 3.91 g of N-bromosuccinimide at room temperature and the mixture was stirred at the same temperature for 2 hours. After completion of the reaction, ethyl acetate was added to the reaction mixture for dilution, and the organic layer was washed with an aqueous solution of potassium carbonate and then with a saturated aqueous solution of sodium chloride and dried over anhydrous magnesium sulfate. The organic layer was concentrated at a reduced pressure, and the residue was subjected to silica gel column chromatography (eluants: ethyl acetate-n-hexane) and crystallized from ether, giving the above-identified compound.
Reaction SMILES: Cl.[F:2][C:3]([F:34])([F:33])[C:4]1[CH:5]=[C:6]([CH:30]=[CH:31][CH:32]=1)[CH2:7][NH:8][CH:9]([C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:15]=1)[C:10]([O:12][CH3:13])=[O:11].[CH3:35][O-].[Na+]>C(O)C.CO>[F:34][C:3]([F:2])([F:33])[C:4]1[CH:5]=[C:6]([CH:30]=[CH:31][CH:32]=1)[CH2:7][NH:8][CH:9]([C:14]1[C:22]2[C:17](=[CH:18][CH:19]=[CH:20][CH:21]=2)[N:16]([CH2:23][C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:15]=1)[C:10]([O:12][CH2:13][CH3:35])=[O:11]
Reactant: C[O-]
Reactant: COC(=O)C(NCc1cccc(C(F)(F)F)c1)c1cn(Cc2ccccc2)c2ccccc12
Agent: Cl
Agent: [Na+]
Solvent: CCO
Solvent: CO
Product: CCOC(=O)C(NCc1cccc(C(F)(F)F)c1)c1cn(Cc2ccccc2)c2ccccc12
Temperature: 25 °C
Reaction time: 2 h

Procedure:
To a magnetically stirred solution of methyl α-[3-(trifluoromethyl)benzylamino-]-1-benzylindole-3-acetate hydrochloride (100 mg) in 8 mL of ethanol was added 70 μL of 25% sodium methoxide in methanol. After stirring at room temperature for two hours, TLC analysis showed 90% conversion to the title compound.
Reaction SMILES: [CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:13]([CH2:14][CH2:15][C:16]([O:18]CC)=[O:17])=[CH:12][N:11]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][CH2:29][C:30]4[N:31]=[C:32]([C:36]5[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=5)[O:33][C:34]=4[CH3:35])=[CH:24][CH:23]=3)[N:10]=2)=[CH:5][CH:4]=1.[OH-].[Na+].C(O)C.Cl>O1CCCC1>[CH3:1][O:2][C:3]1[CH:8]=[CH:7][C:6]([C:9]2[C:13]([CH2:14][CH2:15][C:16]([OH:18])=[O:17])=[CH:12][N:11]([CH2:21][C:22]3[CH:27]=[CH:26][C:25]([O:28][CH2:29][C:30]4[N:31]=[C:32]([C:36]5[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=5)[O:33][C:34]=4[CH3:35])=[CH:24][CH:23]=3)[N:10]=2)=[CH:5][CH:4]=1
Reactant: CCOC(=O)CCc1cn(Cc2ccc(OCc3nc(-c4ccccc4)oc3C)cc2)nc1-c1ccc(OC)cc1
Agent: Cl
Agent: [Na+]
Agent: [OH-]
Solvent: C1CCOC1
Solvent: CCO
Product: COc1ccc(-c2nn(Cc3ccc(OCc4nc(-c5ccccc5)oc4C)cc3)cc2CCC(=O)O)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 81.9 %

Procedure:
A mixture of ethyl 3-[3-(4-methoxyphenyl)-1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-1H-pyrazol-4-yl]propionate (450 mg), 1N aqueous sodium hydroxide solution (2 ml), ethanol (3 ml), and tetrahydrofuran (3 ml) was stirred at room temperature for 1 hour. The reaction mixture was acidified with 1N hydrochloric acid, which was extracted with ethyl acetate. The ethyl acetate layer was washed with saturated aqueous sodium chloride solution, dried (MgSO4), then concentrated. The colorless crystals obtained were collected by filtration to yield 3-[3-(4-methoxyphenyl)-1-[4-(5-methyl-2-phenyl-4-oxazolylmethoxy)benzyl]-1H-pyrazol-4-yl]propionic acid (350 mg, yield: 81%). This was recrystallized from ethyl acetate-hexane. Melting point: 137–138° C.
Reaction SMILES: [S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH:15]=[CH:14][N:13]=[CH:12][CH:11]=1.[CH2:16](Br)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1.[BH4-].[Na+]>CN(C=O)C>[S:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]1[CH2:11][CH2:12][N:13]([CH2:16][C:17]2[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=2)[CH2:14][CH:15]=1
Reactant: BrCc1ccccc1
Reactant: c1ccc2sc(-c3ccncc3)nc2c1
Agent: [BH4-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: C1=C(c2nc3ccccc3s2)CCN(Cc2ccccc2)C1
Yield: 66.9 %

Procedure:
4-(Benzothiazol-2-yl)pyridine (4.5 g, 0.02 mol) was suspended in DMF (10 ml) and benzyl bromide (3.8 ml, 0.03 mol) added and the reaction mixture stirred at reflux for 1 hour. On cooling, the solid was filtered and washed with ether (20 ml). The solid was then suspended in ethanol (100 ml), sodium borohydride (1.05 g, 0.026 mol) added and the reaction stirred at room temperature overnight. The reaction mixture was concentrated in vacuo, the residue diluted with water (50 ml) and the product extracted into dichloromethane (3×50 ml). The combined organic layers were washed with brine, dried (MgSO4), and concentrated. The crude product was purified by flash chromatography eluting with 15% ethyl acetate in petroleum ether to give a solid. Recrystallisation from ethyl acetate afforded the title compound as a white solid (4.1 g, 67%); (Found: C, 74.31; H, 5.87; N, 9.07. C19H18N2S requires C, 74.47; H, 5.92; N, 9.14%). δH (CDCl3), 2.76 (2H, m, NCH2 CH2), 2.83 (2H, m, NCH2CH2), 3.23 (2H, m, NCH2 CH2), 3.67 (2H, s, NCH2Ph), 6.67 (1H, m, NCH2CH), 7.35 (7H, m, ArH), 7.81 (1H, d, J 7.9Hz, ArH), 7.97 (1H, d, J 8.1Hz, ArH). m/z (ES+) 307 (M+1)+.
Reaction SMILES: [N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[S:11]([NH:14][C:15]2[CH:21]=[CH:20][CH:19]=[CH:18][C:16]=2[NH2:17])(=[O:13])=[O:12])[CH:4]=[CH:3][CH:2]=1.[Br:22][C:23]1[CH:28]=[CH:27][CH:26]=[CH:25][C:24]=1[N:29]=[C:30]=[O:31]>>[N:1]1[C:10]2[C:5](=[CH:6][CH:7]=[CH:8][C:9]=2[S:11]([NH:14][C:15]2[CH:21]=[CH:20][CH:19]=[CH:18][C:16]=2[NH:17][C:30]([NH:29][C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][C:23]=2[Br:22])=[O:31])(=[O:12])=[O:13])[CH:4]=[CH:3][CH:2]=1
Reactant: O=C=Nc1ccccc1Br
Reactant: Nc1ccccc1NS(=O)(=O)c1cccc2cccnc12
Product: O=C(Nc1ccccc1Br)Nc1ccccc1NS(=O)(=O)c1cccc2cccnc12
Yield: 46.2 %

Procedure:
The urea was synthesized from 2-((8-quinolinyl)sulfonylamino)aniline(1 mmol) and 2-bromophenylisocyanate(1 mmol) by general Method B. It was purified by dilution with methylene chloride and precipitation with hexane. Filtering afforded the desired compound(0.23 g, 46%). EI-MS m/z 495(M−H)−.
Reaction SMILES: ClC1C=CC=C(C(OO)=[O:9])C=1.[CH3:12][S:13][C:14]1[CH:19]=[CH:18][C:17]([C:20]2[N:21]=[C:22]([CH3:37])[N:23]([C:25]3[CH:26]=[C:27]4[C:32](=[C:33]([CH3:35])[CH:34]=3)[NH:31][C:30](=[O:36])[CH:29]=[CH:28]4)[CH:24]=2)=[CH:16][CH:15]=1.C(=O)([O-])[O-].[Na+].[Na+]>ClCCl>[CH3:12][S:13]([C:14]1[CH:19]=[CH:18][C:17]([C:20]2[N:21]=[C:22]([CH3:37])[N:23]([C:25]3[CH:26]=[C:27]4[C:32](=[C:33]([CH3:35])[CH:34]=3)[NH:31][C:30](=[O:36])[CH:29]=[CH:28]4)[CH:24]=2)=[CH:16][CH:15]=1)=[O:9]
Reactant: CSc1ccc(-c2cn(-c3cc(C)c4[nH]c(=O)ccc4c3)c(C)n2)cc1
Reactant: O=C(OO)c1cccc(Cl)c1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: ClCCl
Product: Cc1cc(-n2cc(-c3ccc(S(C)=O)cc3)nc2C)cc2ccc(=O)[nH]c12
Reaction time: 0.5 h

Procedure:
meta-Chloroperbenzoic acid (0.11 g) was added in portions over a period of 5 minutes to a stirred suspension of 6-(4-[4-methylthiophenyl]-2-methylimidazol-1-yl)-8-methyl-2-(1H)-quinolone (0.2 g) in dichloromethane (10 cm3) at 0°. The mixture was stirred at 0° for 30 minutes, then poured into saturated aqueous sodium carbonate solution (30 cm3) and extracted with dichloromethane (3×25 cm3). The combined and dried (MgSO4) extracts were evaporated in vacuo to give a solid which was recrystallised from dichloromethane to give the title compound, m.p. 313°-5°, (0.08 g).
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6](I)[CH:5]=[CH:4][C:3]=1[CH3:9].[C:10]1(B(O)O)[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=1>C1(C)C=CC=CC=1.C(O)C.C(=O)([O-])[O-].[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[Cl:1][C:2]1[CH:7]=[C:6]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH:5]=[CH:4][C:3]=1[CH3:9]
Reactant: Cc1ccc(I)cc1Cl
Reactant: OB(O)c1ccccc1
Agent: c1ccc([P](c2ccccc2)(c2ccccc2)[Pd]([P](c2ccccc2)(c2ccccc2)c2ccccc2)([P](c2ccccc2)(c2ccccc2)c2ccccc2)[P](c2ccccc2)(c2ccccc2)c2ccccc2)cc1
Agent: O=C([O-])[O-]
Agent: [Na+]
Solvent: CCO
Solvent: Cc1ccccc1
Product: Cc1ccc(-c2ccccc2)cc1Cl
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 99.4 %

Procedure:
To a suspension of tetrakis(triphenylphosphine)palladium (213 mg) in toluene (7 ml) was added 2-chloro-4-iodotoluene (2.33 g) at room temperature. The mixture was stirred at room temperature for 30 min, and a solution of phenylboronic acid (1.35 g) in ethanol (2 ml) and 2 M aqueous sodium carbonate solution (9.25 ml) were added to this mixture, which was followed by reflux under heating. After 3 hr, the reaction mixture was cooled and the organic layer was separated. The aqueous layer was extracted with hexane (4 ml). The organic layers were combined, washed with saturated aqueous sodium hydrogen carbonate solution (4 ml) and saturated brine (4 ml), and dried over anhydrous magnesium sulfate. After filtration, the filtrate was concentrated. To the residue (2.11 g) were added hexane (10 ml) and silica gel (4 g) and the mixture was stirred at room temperature for 1 hr. Silica gel was filtered off and the filtrate was concentrated to give 2-chloro-4-phenyltoluene as a pale-brown oil (1.86 g, 99.4%).