Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [H-].[Na+].[C:3]([O:7][C:8]([NH:10][C:11]1[CH:31]=[CH:30][C:14]([O:15][C:16]2[CH:17]=[CH:18][C:19]([N+:27]([O-:29])=[O:28])=[C:20]([N:22]([CH3:26])[C:23](=[O:25])[O-:24])[CH:21]=2)=[CH:13][CH:12]=1)=[O:9])([CH3:6])([CH3:5])[CH3:4].[CH2:32](Br)[CH2:33][CH2:34][CH2:35][CH2:36][CH3:37]>CN(C)C=O>[C:3]([O:7][C:8]([N:10]([CH2:32][CH2:33][CH2:34][CH2:35][CH2:36][CH3:37])[C:11]1[CH:31]=[CH:30][C:14]([O:15][C:16]2[CH:17]=[CH:18][C:19]([N+:27]([O-:29])=[O:28])=[C:20]([N:22]([CH3:26])[C:23](=[O:24])[O:25][C:3]([CH3:6])([CH3:5])[CH3:4])[CH:21]=2)=[CH:13][CH:12]=1)=[O:9])([CH3:6])([CH3:4])[CH3:5]
Reactant: CN(C(=O)[O-])c1cc(Oc2ccc(NC(=O)OC(C)(C)C)cc2)ccc1[N+](=O)[O-]
Reactant: CCCCCCBr
Agent: [H-]
Agent: [Na+]
Solvent: CN(C)C=O
Product: CCCCCCN(C(=O)OC(C)(C)C)c1ccc(Oc2ccc([N+](=O)[O-])c(N(C)C(=O)OC(C)(C)C)c2)cc1
Temperature: 25 °C
Reaction time: 1 h
Yield: 168.8 %

Procedure:
To a suspension of sodium hydride (55 wt. %, 1.26 g) in anhydrous N,N-dimethylformamide (100 ml) was added N-[5-(4-t-butoxycarbonylaminophenoxy)-2-nitrophenyl]-N-methylcarbamate (12.1 g). The mixture was stirred at ambient temperature for several minutes. To the mixture was added hexyl bromide (6.5 g) under ice cooling and the mixture was stirred at the same temperature for 30 minutes and then at room temperature for 1.0 hour. The reaction mixture was concentrated and the residue was partitioned between ethyl acetate and water. The ethyl acetate layer was dried over anhydrous sodium sulfate and concentrated. The residue was purified by chromatography on a silica gel column using toluene/diisopropyl ether=100/7 as the eluant to give the title compound (13.8 g).
Reaction SMILES: [O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][N:7]1[C:15]([NH:16][CH:17]2[CH2:22][CH2:21][N:20](C(OCC)=O)[CH2:19][CH2:18]2)=[N:14][C:13]2[C:8]1=[N:9][CH:10]=[N:11][CH:12]=2.[OH-].[K+].CC(O)C>O>[OH2:1].[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][N:7]1[C:15]([NH:16][CH:17]2[CH2:18][CH2:19][NH:20][CH2:21][CH2:22]2)=[N:14][C:13]2[C:8]1=[N:9][CH:10]=[N:11][CH:12]=2.[O:1]1[CH:5]=[CH:4][CH:3]=[C:2]1[CH2:6][N:7]1[C:15]([NH:16][CH:17]2[CH2:18][CH2:19][NH:20][CH2:21][CH2:22]2)=[N:14][C:13]2[C:8]1=[N:9][CH:10]=[N:11][CH:12]=2
Reactant: CCOC(=O)N1CCC(Nc2nc3cncnc3n2Cc2ccco2)CC1
Agent: [K+]
Agent: [OH-]
Solvent: CC(C)O
Solvent: O
Product: c1coc(Cn2c(NC3CCNCC3)nc3cncnc32)c1
Reaction time: 48 h

Procedure:
A mixture of 60.5 parts of ethyl 4-[[9-(2-furanylmethyl)-9H-purin-8-yl]amino]-1-piperidinecarboxylate, 90 parts of potassium hydroxide, 800 parts of 2-propanol and 20 parts of water was stirred for 48 hours at reflux temperature. The reaction mixture was evaporated. The reaction mixture was poured into water while stirring. The product was filtered off and dried, yielding a first fraction of 36.2 parts of 9-(2-furanylmethyl)-N-(4-piperidinyl)-9H-purin-8-amine hemihydrate. The aqueous phase was extracted with dichloromethane. The organic layer was dried, filtered and evaporated. The oily residue was stirred in acetonitrile and 2,2'-oxybispropane. The product was filtered off and dried, yielding a second fraction of 5.6 parts of 9-(2-furanylmethyl)-N-(4-piperidinyl)-9H-purin-8-amine. Total yield 41.8 parts (86%) of 9-(2-furanylmethyl)-N-(4-piperidinyl)-9H-purin-8-amine hemihydrate; mp. 164.1° C. (compound 33).
Reaction SMILES: Br[C:2]1[C:7]([Cl:8])=[CH:6][C:5]([Cl:9])=[CH:4][N:3]=1.C[O:11][C:12](=O)[CH:13](NC)[NH:14][C:15](=[O:26])[C:16]1[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=1[C:22]([F:25])([F:24])[F:23].[Cl-].[NH4+].O>O1CCCC1>[Cl:8][C:7]1[C:2]([C:12](=[O:11])[CH2:13][NH:14][C:15](=[O:26])[C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=2[C:22]([F:23])([F:25])[F:24])=[N:3][CH:4]=[C:5]([Cl:9])[CH:6]=1
Reactant: CNC(NC(=O)c1ccccc1C(F)(F)F)C(=O)OC
Reactant: Clc1cnc(Br)c(Cl)c1
Agent: [Cl-]
Agent: [NH4+]
Solvent: C1CCOC1
Solvent: O
Product: O=C(NCC(=O)c1ncc(Cl)cc1Cl)c1ccccc1C(F)(F)F
Temperature: -20 °C
Yield: 23.1 %

Procedure:
To 17.6 g of 2-bromo-3,5-dichloropyridin in 5 ml of tetrahydrofuran, 58.3 ml of a 1.3M tetrahydrofuran solution of isopropylmagnesium chloride-lithium chloride complex was added dropwise with stirring at −20° C., and after the addition, the mixture was stirred at the same temperature for 30 minutes. Then, to the reaction mixture, 10.0 g of N-[2-methoxy(methyl)amino-2-oxoethyl]-2-(trifluoromethyl)benzamide in 57.4 ml of tetrahydrofuran was added dropwise, and after the addition, the mixture was stirred at room temperature for another 3 hours. After completion of the reaction, the reaction mixture was mixed with 100 ml of saturated aqueous ammonium chloride and 100 ml of water and extracted with ethyl acetate (150 ml×2), the resulting organic layers were combined, washed with water (100 ml×1) and dried over saturated aqueous sodium chloride and then anhydrous sodium sulfate, and the solvent was distilled off under reduced pressure. The residue was purified by silica gel column chromatography using ethyl acetate-hexane (with a gradient of from 5:95 to 50:50) as the eluent to obtain 3.0 g of the desired product as pale yellow crystals.
Reaction SMILES: [F:1][C:2]([F:9])([F:8])[C:3]1[CH:7]=[CH:6][NH:5][N:4]=1.Cl[C:11]1[C:16]([Cl:17])=[CH:15][CH:14]=[CH:13][N:12]=1.C(=O)([O-])[O-].[K+].[K+].CN(C)C=O>O>[Cl:17][C:16]1[C:11]([N:5]2[CH:6]=[CH:7][C:3]([C:2]([F:9])([F:8])[F:1])=[N:4]2)=[N:12][CH:13]=[CH:14][CH:15]=1
Reactant: FC(F)(F)c1cc[nH]n1
Reactant: Clc1cccnc1Cl
Agent: O=C([O-])[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: O
Product: FC(F)(F)c1ccn(-c2ncccc2Cl)n1
Temperature: 130 °C
Reaction time: 14 h
Yield: 82.2 %

Procedure:
A mixture of 15.30 g of 3-trifluoromethyl-1H-pyrazole, 16.64 g of 2,3-dichloropyridine, 26.42 g of potassium carbonate and 100 ml of N,N-dimethylformamide was stirred at 130° C. for 14 hours. The reaction mixture was allowed to cool to room temperature and then water was poured thereto. The mixture was extracted with ethyl acetate two times. The organic layers were combined, washed successively with water and an aqueous saturated sodium chloride solution, dried over magnesium sulfate, and concentrated under reduced pressure. The resulting residue was subjected to silica gel column chromatography to obtain 22.88 g of 3-chloro-2-(3-trifluoromethyl-1H-pyrazol-1-yl)pyridine of the formula:
Reaction SMILES: [CH3:1][C:2]1[CH:3]=[C:4]2[CH:8]([C:9]([O:11][CH:12]([CH3:14])[CH3:13])=[O:10])[CH2:7][CH2:6][N:5]2[CH:15]=1.CN(C)[C:18]([C:20]1[S:21][CH:22]=[CH:23][CH:24]=1)=[O:19]>>[C:20]1([C:18]([C:15]2[N:5]3[CH2:6][CH2:7][CH:8]([C:9]([O:11][CH:12]([CH3:13])[CH3:14])=[O:10])[C:4]3=[CH:3][C:2]=2[CH3:1])=[O:19])[S:21][CH:22]=[CH:23][CH:24]=1
Reactant: CN(C)C(=O)c1cccs1
Reactant: Cc1cc2n(c1)CCC2C(=O)OC(C)C
Product: Cc1cc2n(c1C(=O)c1cccs1)CCC2C(=O)OC(C)C

Procedure:
In accordance with the method of Example 9, isopropyl 1,2-dihydro-6-methyl-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate is condensed with N,N-dimethylthiophene-2-carboxamide to produce isopropyl 5-(2-thenoyl)-1,2-dihydro-6-methyl-3H-pyrrolo[1,2-a]pyrrole-1-carboxylate (XI, R = CH3, R1 = H, R2 = iC3H7, X = S), having a melting point of 102.5° C.
Reaction SMILES: [CH2:1]([NH:8][CH2:9][C@H:10]1[CH2:15][O:14][C:13]2[CH:16]=[CH:17][C:18]([N+:24]([O-])=O)=[C:19]([CH2:20][C:21](O)=[O:22])[C:12]=2[O:11]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O.[C:28]1([CH3:38])[CH:33]=[CH:32][C:31]([S:34]([OH:37])(=[O:36])=[O:35])=[CH:30][CH:29]=1>[Pt].CO>[CH3:38][C:28]1[CH:29]=[CH:30][C:31]([S:34]([OH:37])(=[O:36])=[O:35])=[CH:32][CH:33]=1.[CH2:1]([NH:8][CH2:9][C@@H:10]1[O:11][C:12]2=[C:19]3[C:18](=[CH:17][CH:16]=[C:13]2[O:14][CH2:15]1)[NH:24][C:21](=[O:22])[CH2:20]3)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: O=C(O)Cc1c([N+](=O)[O-])ccc2c1O[C@@H](CNCc1ccccc1)CO2
Agent: [Pt]
Agent: Cc1ccc(S(=O)(=O)O)cc1
Solvent: CO
Solvent: O
Product: O=C1Cc2c(ccc3c2O[C@@H](CNCc2ccccc2)CO3)N1
Temperature: 50 °C
Reaction time: 18 h
Yield: 61.1 %

Procedure:
A 50 mL two necked flask equipped with a magnetic stir bar, gas inlet adapter and gas outlet adapter is charged with {(3S)-3-[(benzylamino)methyl]-6-nitro-2,3-dihydro-1,4-benzodioxin-5-yl}acetic acid [from above (1.36 g, 3.80 mmol)], methanol (20 mL), and p-toluenesulfonic acid monohydrate (1.80 g, 9.5 mmol) and platinum (5% on carbon, 62% w/w water, 0.27 g). The flask head space is flushed with hydrogen gas (100 mL), the gas outlet adapter is closed and the slurry is stirred under a hydrogen atmosphere for 18 h under hydrogen, at which point the reaction is complete by LCMS. The catalyst is removed by vacuum filtration, and the resulting solution is heated to 50° C. (external) in an oil bath for 48 h. The solids are collected by vacuum filtration, the filter cake is washed with cold MeOH (10 mL) and dried under nitrogen giving (2S)-2-[(benzylamino)methyl]-2,3,8,9-tetrahydro-7H-[1,4]dioxino[2,3-e]indol-8-one 4-methylbenzenesulfonate (1.12 g, 61%) as an off-white powder.
Reaction SMILES: Cl([O-])(=O)(=O)=O.Cl[C:7]1[CH2:12][C:11]([CH3:14])([CH3:13])[CH2:10][C:9](=[N+:15]2[CH2:19][CH2:18][CH2:17][CH2:16]2)[CH:8]=1.[CH2:20]([N:22]1[C:26](=[O:27])[CH2:25][S:24][C:23]1=[S:28])[CH3:21].C(N(CC)CC)C>C(O)C>[CH2:20]([N:22]1[C:26](=[O:27])[C:25](=[C:7]2[CH2:12][C:11]([CH3:14])([CH3:13])[CH2:10][C:9]([N:15]3[CH2:19][CH2:18][CH2:17][CH2:16]3)=[CH:8]2)[S:24][C:23]1=[S:28])[CH3:21]
Reactant: CC1(C)CC(Cl)=CC(=[N+]2CCCC2)C1
Reactant: CCN1C(=O)CSC1=S
Agent: [O-][Cl+3]([O-])([O-])[O-]
Solvent: CCN(CC)CC
Solvent: CCO
Product: CCN1C(=O)C(=C2C=C(N3CCCC3)CC(C)(C)C2)SC1=S

Procedure:
N-(3-Chloro-5,5-dimethylcyclohex-2-en-1-ylidene)-pyrrolidinium perchlorate (3.1 g., 0.01 mol.), 3-ethylrhodanine (1.6 g., 0.011 mol.) and triethylamine (3.1 ml.) are dissolved in ethanol (20 ml.) and heated at reflux for 10 minutes. After chilling, the solid is collected on a filter, rinsed with ethanol and dried. After one recrystallization from pyridine/methanol, the yield of purified dye is 2.2 g. (65%), m.p. 234°-235°C. with decomposition. This dye is an excellent spectral sensitizer for photographic silver halide emulsions in the minus blue region of the spectrum as set forth in Table 2 hereinafter.
Reaction SMILES: [C:1](=[N:14][NH:15][C:16]1[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CCOC(C)=O.CC[CH2:31][CH2:32][CH2:33][CH2:34][CH3:35]>>[C:1](=[N:14][N:15]([C:16]1[CH:17]=[CH:18][C:19]([Cl:22])=[CH:20][CH:21]=1)[CH2:35][CH:34]1[CH2:31][CH2:32][CH2:33]1)([C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][CH:9]=1)[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1
Reactant: CCCCCCC
Reactant: Clc1ccc(NN=C(c2ccccc2)c2ccccc2)cc1
Solvent: CCOC(C)=O
Product: Clc1ccc(N(CC2CCC2)N=C(c2ccccc2)c2ccccc2)cc1

Procedure:
Rf=0.77. (30/70 EtOAc/heptane (v/v)) (immediate deprotection). N-Benzhydrylidene-N′-(4-chlorophenyl)hydrazine is described in example 28.
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[N:4][C:5]2[C:10]([C:11]=1[NH:12][CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)=[CH:9][CH:8]=[CH:7][CH:6]=2.[C:20](OCC)(OCC)([O:22]CC)[CH3:21]>C(O)(=O)C>[OH2:22].[CH2:13]([N:12]1[C:11]2[C:10]3[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=3[N:4]=[CH:3][C:2]=2[N:1]=[C:20]1[CH3:21])[C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1
Reactant: CCOC(C)(OCC)OCC
Reactant: Nc1cnc2ccccc2c1NCc1ccccc1
Solvent: CC(=O)O
Product: Cc1nc2cnc3ccccc3c2n1Cc1ccccc1
Product: O

Procedure:
Using the method of Example 49, 3-amino-4-(benzylamino)quinoline (from Example 127, Part B), was reacted with triethyl orthoacetate and acetic acid to provide 1-benzyl-2-methyl-1H-imidazo[4,5-c]quinoline hydrate, m.p. 145°-147° C. Analysis: Calculated for C18H15N3.2.25H2O: %C, 68.9; %H, 6.3, %N, 13.4; Found: %C, 69.2; %H, 6.0; %N 13.4.
Reaction SMILES: [NH2:1][C@H:2]([C@@H:10]([OH:21])[CH2:11][C@@H:12]([NH2:20])[CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1.C1(OB(O)O)C=CC=CC=1.O.C1C([N+]([O-])=O)=CC=C([O:42][C:43]([O:45][CH2:46][C:47]2[O:51][N:50]=[CH:49][CH:48]=2)=O)C=1>C1(C)C=CC=CC=1.C1COCC1>[NH2:20][C@@H:12]([CH2:13][C:14]1[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=1)[CH2:11][C@H:10]([OH:21])[C@@H:2]([NH:1][C:43]([O:45][CH2:46][C:47]1[O:51][N:50]=[CH:49][CH:48]=1)=[O:42])[CH2:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][CH:5]=1
Reactant: N[C@@H](Cc1ccccc1)C[C@H](O)[C@@H](N)Cc1ccccc1
Reactant: O=C(OCc1ccno1)Oc1ccc([N+](=O)[O-])cc1
Agent: OB(O)Oc1ccccc1
Solvent: O
Solvent: Cc1ccccc1
Solvent: C1CCOC1
Product: N[C@@H](Cc1ccccc1)C[C@H](O)[C@H](Cc1ccccc1)NC(=O)OCc1ccno1
Temperature: -40 °C
Reaction time: 1 h

Procedure:
A mixture of 1.54 g (5.41 mmol) of (2S,3S,5S)-2,5-diamino-1,6-diphenyl-3-hydroxyhexane and 0.673 g (5.41 mmol) of phenylboric acid in anhydrous toluene (130 mL) was heated at reflux under argon for 2 hrs with removal of H2O by a Dean-Slark trap. The resulting yellow solution was allowed to cool and the solvent was removed in vacuo to give an oil which solidified upon standing. The residue was taken up in 90 ml of THF, cooled to -40° C., and treated dropwise under Ar atmosphere over a period of 1 h with 1.11 g (3.78 mmol) of ((5-isoxazolyl)methyl)-(4-nitrophenyl)carbonate in 40 ml of THF. The solution was allowed to warm to -20° C. over the next 0.5 hr, then was stirred at 0° C. for 2.5 hrs and at room temperature for 1 hr. After removal of the solvent in vacuo, the residue was taken up in ethyl acetate (200 mL), washed sequentially with 5% aqueous K2CO3 (4×25 mL) and saturated brine (25 mL), dried over Na2So4 and concentrated in vacuo. Silica gel chromatography of the residue using a gradient of methanol in chloroform (2%, 4%, 6%) afforded a mixture of the desired product and its regioisomer. Purification of the mixture on two consecutive 250 g SiO2 columns (deactivated with 1% isopropylamine/CH2Cl2) with a gradient of isopropylamine/CH2Cl2 (0.5%, 1%) afforded the desired compound as a sticky solid (0.730 g, 1.78 mmol, 33%): 1H NMR (DMSO-d6) δ1.17-1.57 (m, 5H), 2.56-2.69 (m, 2H), 2.75-2.86 (m, 1H), 2.89-3.00 (m, 2H), 3.53-3.71 (m, 3H), 5.06 (s, 2H), 6.32 (d, J=2.4 Hz, 1H), 7.11-7.30 (m, 10H), 8.54 (d, J=2.4 Hz, 1H). Mass spectrum: (M+H)+ =410.
Reaction SMILES: Br[CH2:2][CH2:3][OH:4].Cl[S:6]([N:9]=[C:10]=[O:11])(=[O:8])=[O:7].[NH2:12][CH:13]([CH2:21][C:22]1[CH:23]=[N:24][C:25]([NH:28][C:29]([O:31][C:32]([CH3:35])([CH3:34])[CH3:33])=[O:30])=[CH:26][CH:27]=1)[C:14]([O:16][C:17]([CH3:20])([CH3:19])[CH3:18])=[O:15].C(N(CC)CC)C>ClCCl>[C:32]([O:31][C:29]([NH:28][C:25]1[N:24]=[CH:23][C:22]([CH2:21][CH:13]([NH:12][S:6]([N:9]2[CH2:2][CH2:3][O:4][C:10]2=[O:11])(=[O:8])=[O:7])[C:14]([O:16][C:17]([CH3:18])([CH3:19])[CH3:20])=[O:15])=[CH:27][CH:26]=1)=[O:30])([CH3:35])([CH3:34])[CH3:33]
Reactant: CC(C)(C)OC(=O)Nc1ccc(CC(N)C(=O)OC(C)(C)C)cn1
Reactant: O=C=NS(=O)(=O)Cl
Reactant: OCCBr
Solvent: CCN(CC)CC
Solvent: ClCCl
Product: CC(C)(C)OC(=O)Nc1ccc(CC(NS(=O)(=O)N2CCOC2=O)C(=O)OC(C)(C)C)cn1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 36.9 %

Procedure:
A solution of 0.126 ml of 2-bromoethanol (1.78 mmol, 1.0 equiv.) in dichloromethane (10 ml) was slowly added dropwise to a solution of 251 mg of chlorosulfonyl isocyanate (1.78 mmol, 1.0 equiv.) in dichloromethane (10 ml) under argon at 0° C. in such a way that the temperature did not exceed 10° C. After the addition, the mixture was stirred at 0° C. for a further 30 min. A mixture of 600 mg of tert-butyl 2-amino-3-(6-tert-butoxycarbonylamino-pyridin-3-yl)-propionate (1.78 mmol, 1.0 equiv.) and 0.545 ml of triethylamine (3.91 mmol, 2.2 equiv.) in 5 ml of CH2Cl2 was added dropwise to this solution in such a way that the temperature did not rise above 10° C. After the addition, the ice bath was removed and the mixture was stirred at RT for a further 3 h. The residue after concentration was chromatographed on silica gel with heptane/ethyl acetate mixtures as eluent. 320 mg (37% yield) of the title compound were obtained as a colorless solid.
Reaction SMILES: [CH3:1][N:2]1[CH:6]=[C:5]([N+:7]([O-:9])=[O:8])[CH:4]=[C:3]1[C:10]([OH:12])=O.S(Cl)(Cl)=O.[CH3:17][N:18]1[CH:22]=[C:21]([N+:23]([O-:25])=[O:24])[CH:20]=[C:19]1[C:26](Cl)=[O:27].[NH2:29][C:30]1[CH:31]=[C:32]([CH:36]=[CH:37][C:38]=1[NH2:39])[C:33]([OH:35])=[O:34]>>[NH2:29][C:30]1[CH:31]=[C:32]([CH:36]=[CH:37][C:38]=1[NH:39][C:10]([C:3]1[N:2]([CH3:1])[CH:6]=[C:5]([N+:7]([O-:9])=[O:8])[CH:4]=1)=[O:12])[C:33]([OH:35])=[O:34].[NH2:39][C:38]1[CH:37]=[CH:36][C:32]([C:33]([OH:35])=[O:34])=[CH:31][C:30]=1[NH:29][C:26]([C:19]1[N:18]([CH3:17])[CH:22]=[C:21]([N+:23]([O-:25])=[O:24])[CH:20]=1)=[O:27]
Reactant: Cn1cc([N+](=O)[O-])cc1C(=O)Cl
Reactant: Cn1cc([N+](=O)[O-])cc1C(=O)O
Reactant: Nc1ccc(C(=O)O)cc1N
Solvent: O=S(Cl)Cl
Product: Cn1cc([N+](=O)[O-])cc1C(=O)Nc1cc(C(=O)O)ccc1N
Product: Cn1cc([N+](=O)[O-])cc1C(=O)Nc1ccc(C(=O)O)cc1N

Procedure:
As a further alternative, the compound of the formula (14) can also be synthesized as will be described next. For example, 1-methyl-4-nitro-2-pyrrolecarboxylic acid is reacted, by using the process disclosed in Tetrahedron, 34, 2389-2391(1978), with thionyl chloride into 1-methyl-4-nitro-2-pyrrolecarboxylic acid chloride, which is then reacted with a 3,4-diaminobenzoic acid to obtain 3-amino-4-(1-methyl-4-nitro-2-pyrrolecarboxamido)benzoic acid or 4-amino-3-(1-methyl-4-nitro-2-pyrrolecarboxamido)benzoic acid as the exemplified compound. Here, the reaction product can also be a mixture of both the benzoic acids. Methylene chloride, chloroform, DMF or the like can be used as a solvent. Other solvents are also usable as long as they do not take part in the reactions. Heating of the thus-obtained amide compound with trilfluoroacetic acid with any solvent, which do not participate in the reaction, provides 1H-2-(1-methyl-4-nitropyrrol-2-yl)benzimidazole-5-carboxylic acid. Further, 1-methyl-4-nitro-2-trichloroacetylpyrrole which is a known compound disclosed in Heterocycles, 27, 1945-1952(1988) is likewise reacted with 3,4-diaminobenzoic acid to obtain 3-amino-4-(1-methyl-4-nitro-2-pyrrolecarboxamido)-benzoic acid or 4-amino-3-(1-methyl-4-nitro-2-pyrrolecarboxamido)benzoic acid. Here, the reaction product can also be a mixture of both the benzoic acids. The reaction product can also be converted into 1H-2-(1-methyl-4-nitropyrrole-2-yl)benzimidazole-5-carboxylic acid likewise. The reaction can also be conducted similarly by using as a starting material an equivalent carboxylic acid other than 1-methylpyrrole-2-carboxylic acid.
Reaction SMILES: [CH3:1][CH:2]1[CH2:8][C:7]2[CH:9]=[C:10]3[O:15][CH2:14][O:13][C:11]3=[CH:12][C:6]=2[C:5]([C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=2)=[N:4][N:3]1[C:25](=[N:27][OH:28])[NH2:26].[CH:29](OCC)(OCC)OCC.Cl>>[CH3:1][CH:2]1[CH2:8][C:7]2[CH:9]=[C:10]3[O:15][CH2:14][O:13][C:11]3=[CH:12][C:6]=2[C:5]([C:16]2[CH:21]=[CH:20][C:19]([N+:22]([O-:24])=[O:23])=[CH:18][CH:17]=2)=[N:4][N:3]1[C:25]1[N:26]=[CH:29][O:28][N:27]=1
Reactant: CCOC(OCC)OCC
Reactant: CC1Cc2cc3c(cc2C(c2ccc([N+](=O)[O-])cc2)=NN1C(N)=NO)OCO3
Agent: Cl
Product: CC1Cc2cc3c(cc2C(c2ccc([N+](=O)[O-])cc2)=NN1c1ncon1)OCO3
Temperature: 110 °C
Reaction time: 0.5 h
Yield: 75 %

Procedure:
A mixture of 1.50 g (3.91 mmol) of the starting material XXIV and 15 ml of triethyl orthoformate in the presence of 0.05 ml of 36% hydrochloric acid was stirred at 110° C. for 30 min, then concentrated in vacuum. The residue was stirred with water, the precipitated crystals were filtered off, washed with water and recrystallized from 2-methoxyethanol to yield 1.15 g (75%) of the title compound; Mp.: 190-196° C.
Reaction SMILES: [CH:1]1([CH:7]([C:9]2[C:10]([CH3:25])=[N:11][N:12]([C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=3)[CH:13]=2)O)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[NH2:26][C:27]1[CH:32]=[CH:31][C:30]([C:33]([N:35]([CH3:43])[CH2:36][CH2:37][C:38]([O:40]CC)=[O:39])=[O:34])=[CH:29][CH:28]=1>>[CH:1]1([CH:7]([NH:26][C:27]2[CH:28]=[CH:29][C:30]([C:33]([N:35]([CH3:43])[CH2:36][CH2:37][C:38]([OH:40])=[O:39])=[O:34])=[CH:31][CH:32]=2)[C:9]2[C:10]([CH3:25])=[N:11][N:12]([C:14]3[CH:19]=[CH:18][C:17]([O:20][C:21]([F:24])([F:23])[F:22])=[CH:16][CH:15]=3)[CH:13]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1
Reactant: Cc1nn(-c2ccc(OC(F)(F)F)cc2)cc1C(O)C1CCCCC1
Reactant: CCOC(=O)CCN(C)C(=O)c1ccc(N)cc1
Product: Cc1nn(-c2ccc(OC(F)(F)F)cc2)cc1C(Nc1ccc(C(=O)N(C)CCC(=O)O)cc1)C1CCCCC1
Yield: 92.5 %

Procedure:
Using cyclohexyl{3-methyl-1-[4-(trifluoromethoxy)phenyl]-1H-pyrazol-4-yl}methanol (0.97 g) synthesized in Example 25(3) and ethyl 3-{[(4-aminophenyl)carbonyl](methyl)amino}propanoate (0.63 g) synthesized in Example 2(2) and in the same manner as in Example 1(7), the title object compound (1.3 g, 63%) was obtained as a white solid.
Reaction SMILES: [Br:1][C:2]1[C:10]([F:11])=[CH:9][C:5]([C:6]([OH:8])=[O:7])=[C:4]([N+:12]([O-:14])=[O:13])[CH:3]=1.[C:15](=O)([O-])[O-].[K+].[K+].CI>CN(C=O)C>[Br:1][C:2]1[C:10]([F:11])=[CH:9][C:5]([C:6]([O:8][CH3:15])=[O:7])=[C:4]([N+:12]([O-:14])=[O:13])[CH:3]=1
Reactant: O=C([O-])[O-]
Reactant: O=C(O)c1cc(F)c(Br)cc1[N+](=O)[O-]
Agent: [K+]
Solvent: CN(C)C=O
Solvent: CI
Product: COC(=O)c1cc(F)c(Br)cc1[N+](=O)[O-]
Temperature: 0 °C
Reaction time: 0.25 h
Yield: 94.3 %

Procedure:
To a stirred solution of 4-bromo-5-fluoro-2-nitrobenzoic acid (Ark Pharm, 5.387 g, 20.40 mmol) in DMF (80.0 mL) at 0° C. was added potassium carbonate (5.870 g, 42.47 mmol), followed by methyl iodide (8.789 g, 61.92 mmol). After stirring at 0° C. for 15 min., the reaction was heated to 40° C. for 2 h. The mixture was filtered and concentrated. The residue was dissolved in EtOAc (150 mL), washed with water (2×100 mL), brine (100 mL), dried over Na2SO4, and concentrated under reduced pressure. The resulting residue was purified by flash chromatography on silica gel (0-50% EtOAc in hexanes) to give the sub-title compound as a pale yellow oil (5.348 g, 94%). LCMS calc. for C8H6BrFNO4 (M+H)+: m/z=277.9. found no ionization.
Reaction SMILES: [CH2:1]1[CH2:10][N:9]2[CH:11]=[CH:12][C:7]3=[C:8]2[C:3](=[CH:4][CH:5]=[CH:6]3)[CH2:2]1.[C:13](Cl)(=[O:17])[C:14](Cl)=[O:15].[CH3:19][OH:20]>>[C:12]1([C:13](=[O:17])[C:14]([O:20][CH3:19])=[O:15])[C:7]2=[C:8]3[C:3](=[CH:4][CH:5]=[CH:6]2)[CH2:2][CH2:1][CH2:10][N:9]3[CH:11]=1
Reactant: c1cc2c3c(c1)ccn3CCC2
Reactant: CO
Reactant: O=C(Cl)C(=O)Cl
Product: COC(=O)C(=O)c1cn2c3c(cccc13)CCC2

Procedure:
In one aspect, Step 1 is the reaction of lilolidine with oxalyl chloride in an inert solvent and methanol to form compound C. In one aspect, the amount of oxalyl chloride used with respect to lilolidine is about 1.0 to about 1.2 equivalents. In another aspect, the amount of oxalyl chloride to lilolidine is about 1.05 equivalents.
Reaction SMILES: Cl[C:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[S:5][CH2:4][C:3]=1[CH:12]=O.[SH:14][CH:15]([CH2:19][C:20]([OH:22])=[O:21])C(O)=O.C(N(CC)CC)C.Cl>CS(C)=O.O>[S:14]1[C:2]2[C:11]3[CH:10]=[CH:9][CH:8]=[CH:7][C:6]=3[S:5][CH2:4][C:3]=2[CH:12]=[C:15]1[CH2:19][C:20]([OH:22])=[O:21]
Reactant: O=CC1=C(Cl)c2ccccc2SC1
Reactant: O=C(O)CC(S)C(=O)O
Agent: Cl
Solvent: CCN(CC)CC
Solvent: CS(C)=O
Solvent: O
Product: O=C(O)Cc1cc2c(s1)-c1ccccc1SC2
Reaction time: 0.5 h

Procedure:
To a stirred solution of 21 g 4-chloro-3-formyl-thiochrom-3-ene in 80 ml dry dimethylsulfoxide under nitrogen is added 15 g mercaptosuccinic acid. 36 ml triethylamine is then added dropwise and subsequently the reaction mixture is kept at 90°-100° C. for 30 minutes. The mixture is then diluted with water, acidified with hydrochloric acid and extracted with diethylether. The organic layer is then extracted with aqueous sodium bicarbonate solution. After acidification of the aqueous layer the product precipitates as a tar. It is taken up in chloroform. After evaporation of the solvent the residue is recrystallized from a mixture of chloroform and cyclohexane. Pure (4H-thieno[3,2-c][1]benzothiopyran-2-yl)acetic acid is obtained; m.p. 106°-110° C.