Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [C:1]1(=[O:11])[O:6][C:4](=O)[C@H:3]2[CH2:7][CH:8]=[CH:9][CH2:10][C@@H:2]12.[NH2:12][CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]([OH:20])=[O:19]>C(O)(=O)C>[C:4]1(=[O:6])[N:12]([CH2:13][CH2:14][CH2:15][CH2:16][CH2:17][C:18]([OH:20])=[O:19])[C:1](=[O:11])[C@H:2]2[CH2:10][CH:9]=[CH:8][CH2:7][C@@H:3]12
Reactant: O=C1OC(=O)[C@@H]2CC=CC[C@H]12
Reactant: NCCCCCC(=O)O
Solvent: CC(=O)O
Product: O=C(O)CCCCCN1C(=O)[C@H]2CC=CC[C@H]2C1=O
Temperature: 4 °C

Procedure:
31 g (0.2 mole) of cis-1,2,3,6-tetrahydrophthalic anhydride and 26.2 g (0.2 mole) of 6-aminohexanoic acid are dissolved in 400 ml. of acetic acid and warmed 3 hours on a steam bath. The cooled solution is concentrated to remove most of the acetic acid and the residue taken up in 200 ml. of methylene chloride. The solution is washed twice with water and dried over sodium sulfate. The solvent is removed and the residue taken up in 500 ml toluene. Para-toluenesulfonic acid (1 g) is added to the solution, followed by reflux for 10 hrs. with a Dean-Stark water trap. The solution is cooled and concentrated to about 50 ml and diluted with 50 ml of hexane. The mixture is shaken for a few minutes until the oil crystallizes then cooled at 4° C. for several hours, filtered and dried at 50° C. The light yellow crystals (32 g) are taken up in chloroform and filtered to remove any precipitate. The solution is diluted with hexane near the cloud point, cooled until a crystalline mass accumulates, filtered and dried to yield white crystals, m.p. 85°-87° C.
Reaction SMILES: [NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[NH:14][C:15](=[O:33])[C:16]([C:19]1[CH:24]=[C:23]([C:25]([F:28])([F:27])[F:26])[CH:22]=[C:21]([C:29]([F:32])([F:31])[F:30])[CH:20]=1)([CH3:18])[CH3:17].CI.[C:36](OCC)(=O)C>CN(C)C=O>[NH2:1][C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][C:3]=1[C:8]1[CH:13]=[CH:12][CH:11]=[CH:10][C:9]=1[N:14]([CH3:36])[C:15](=[O:33])[C:16]([C:19]1[CH:20]=[C:21]([C:29]([F:30])([F:31])[F:32])[CH:22]=[C:23]([C:25]([F:26])([F:27])[F:28])[CH:24]=1)([CH3:18])[CH3:17]
Reactant: CC(C)(C(=O)Nc1ccccc1-c1ccccc1N)c1cc(C(F)(F)F)cc(C(F)(F)F)c1
Reactant: CCOC(C)=O
Solvent: CN(C)C=O
Solvent: CI
Product: CN(C(=O)C(C)(C)c1cc(C(F)(F)F)cc(C(F)(F)F)c1)c1ccccc1-c1ccccc1N
Reaction time: 1 h
Yield: 36 %

Procedure:
To a solution of 151 mg (0.32 mmol) N-(2′-amino-biphenyl-2-yl)-2-(3,5bis-trifluoromethyl-phenyl)-isobutyramide in 1 ml N,N-dimethylformamide under argon 130 mg (0.65 mmol) potassium hexamethyldisilazide were added at 0°. Stirring was continued for 1 h at room temperature and the reaction mixture was cooled to 0° again. At this temperature, 115 mg (0.81 mmol) methyl iodide were added. After stirring for 3 hrs at room temperature, ethyl acetate was added and the organic layer was washed with brine, dried (MgSO4) and evaporated. The residue was purified by chromatography (SiO2, ethyl acetate/CH2Cl21:1) to give 56 mg (36%) N-(2′-amino-biphenyl-2-yl)-2-(3,5-bis-trifluoromethyl-phenyl)-N-methyl-isobutyramide as colorless oil, MS(ISP): 481.1(M+H)+.
Reaction SMILES: Br[CH2:2][C:3](=O)[C:4](=[N:35][O:36][CH2:37][C:38]([O:40][CH2:41][C:42]([Cl:45])([Cl:44])[Cl:43])=[O:39])[C:5]([NH:7][CH:8]1[C:33](=[O:34])[N:10]2[C:11]([C:17]([O:19][CH:20]([C:27]3[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=3)[C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)=[O:18])=[C:12]([CH:15]=[CH2:16])[CH2:13][S:14][C@H:9]12)=[O:6].[NH2:47][C:48]([NH2:50])=[S:49].C([O-])(=O)C.[Na+]>O1CCCC1.O>[NH2:50][C:48]1[S:49][CH:2]=[C:3]([C:4](=[N:35][O:36][CH2:37][C:38]([O:40][CH2:41][C:42]([Cl:44])([Cl:45])[Cl:43])=[O:39])[C:5]([NH:7][CH:8]2[C:33](=[O:34])[N:10]3[C:11]([C:17]([O:19][CH:20]([C:21]4[CH:22]=[CH:23][CH:24]=[CH:25][CH:26]=4)[C:27]4[CH:28]=[CH:29][CH:30]=[CH:31][CH:32]=4)=[O:18])=[C:12]([CH:15]=[CH2:16])[CH2:13][S:14][C@H:9]23)=[O:6])[N:47]=1
Reactant: NC(N)=S
Reactant: C=CC1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)C(NC(=O)C(=NOCC(=O)OCC(Cl)(Cl)Cl)C(=O)CBr)[C@H]2SC1
Agent: CC(=O)[O-]
Agent: [Na+]
Solvent: O
Solvent: C1CCOC1
Product: C=CC1=C(C(=O)OC(c2ccccc2)c2ccccc2)N2C(=O)C(NC(=O)C(=NOCC(=O)OCC(Cl)(Cl)Cl)c3csc(N)n3)[C@H]2SC1
Temperature: 35 °C
Reaction time: 3 h
Yield: 49.5 %

Procedure:
To a solution of benzhydryl 7-[4-bromo-2-(2,2,2-trichloroethoxycarbonylmethoxyimino)-3-oxobutyramido]-3-vinyl-3-cephem-4-carboxylate (26.0 g) in tetrahydrofuran (100 ml) was added a solution of thiourea (3.1 g) and sodium acetate (3.3 g) in water (100 ml), and the mixture was stirred at 35° C. for 3 hours. The reaction mixture was extracted with ethyl acetate, and the extract was washed with water, followed by drying over magnesium sulfate. Removal of the solvent gave benzhydryl 7-[2-(2-aminothiazol-4-yl)-2-(2,2,2-trichloroethoxycarbonylmethoxyimino)acetamido]-3-vinyl-3-cephem-4-carboxylate (syn isomer) (12.5 g).
Reaction SMILES: [Br:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[CH:9]([NH2:15])[CH2:8][CH2:7][CH2:6][C:5]2=1.[C:16](Cl)(=[O:25])[C:17]1[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=1>>[Br:1][C:2]1[CH:3]=[C:4]2[C:12](=[CH:13][CH:14]=1)[NH:11][C:10]1[CH:9]([NH:15][C:16](=[O:25])[C:17]3[CH:22]=[CH:21][C:20]([O:23][CH3:24])=[CH:19][CH:18]=3)[CH2:8][CH2:7][CH2:6][C:5]2=1
Reactant: NC1CCCc2c1[nH]c1ccc(Br)cc21
Reactant: COc1ccc(C(=O)Cl)cc1
Product: COc1ccc(C(=O)NC2CCCc3c2[nH]c2ccc(Br)cc32)cc1

Procedure:
N-(6-Bromo-2,3,4,9-tetrahydro-1H-carbazol-1-yl)-4-methoxybenzamide was prepared from 6-bromo-2,3,4,9-tetrahydro-1H-carbazol-1-amine and p-anisoyl chloride in a similar manner as described above to give a white solid (11% yield). 1H-NMR (DMSO-de): 810.99 (s, 1H), 8.70 (d, 1H), 7.96 (d, 2H), 7.60 (d, 1H), 7.29 (d, 1H), 7.16 (dd, 1H), 7.02 (d, 2H), 5.38 (m, 1H), 2.67 (m, 2H), 2.08 (m, 2H), 1.87 (m, 2H); MS m/z 399 (M−1).
Reaction SMILES: [CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([C:14](=[N:25][NH2:26])[C:15]2[C:20](Cl)=[CH:19][N:18]=[C:17]3[NH:22][CH:23]=[CH:24][C:16]=23)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.CC(C)([O-])C.[Na+].CO>CN1C(=O)CCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH2:1]([N:8]1[CH2:13][CH2:12][CH2:11][CH:10]([C:14]2[C:15]3=[C:16]4[CH:24]=[CH:23][NH:22][C:17]4=[N:18][CH:19]=[C:20]3[NH:26][N:25]=2)[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: NN=C(c1c(Cl)cnc2[nH]ccc12)C1CCCN(Cc2ccccc2)C1
Agent: [Pd+2]
Agent: CC(=O)[O-]
Agent: CC(C)(C)[O-]
Solvent: CN1CCCC1=O
Solvent: CO
Product: c1ccc(CN2CCCC(c3n[nH]c4cnc5[nH]ccc5c34)C2)cc1
Temperature: 160 °C
Yield: 19 %

Procedure:
A mixture of 4-((1-benzylpiperidin-3-yl)(hydrazono)methyl)-5-chloro-1H-pyrrolo[2,3-b]pyridine (1.04 g, 2.84 mmol), sodium tert-butoxide (0.652 g, 6.78 mmol), palladium acetate (0.0064 g, 0.028 mmol) and (R)-1-[(S)-2-(dicyclohexylphosphino)ferrocenyl]ethyl-di-tert-butyl phosphine (0.016 g, 0.028 mmol) in NMP (10 mL) was heated in the microwave at about 160° C. for about 30 min. Additional palladium acetate (0.0064 g, 0.028 mmol) and (R)-1-[(S)-2-(dicyclohexylphosphino)ferrocenyl]ethyl-di-tert-butyl phosphine (0.016 g, 0.028 mmol) were added and the mixture was heated in a microwave at about 160° C. for about 15 min. Additional palladium acetate (0.003 g, 0.014 mmol) and (R)-1-[(S)-2-(dicyclohexylphosphino)ferrocenyl]ethyl-di-tert-butyl phosphine (0.008 g, 0.014 mmol) were added and the mixture was again heated at about 160° C. for about 8 min. The solvent was removed under reduced pressure and the residue was partitioned between water (25 mL) and EtOAc (25 mL). The organic phase was washed with brine (20 mL), dried over anhydrous MgSO4, decolorized with charcoal and filtered. The solvent was removed under reduced pressure and the residue purified by silica gel chromatography, eluting first with DCM (1 L), a mixture of 98:1:1 DCM:TEA:MeOH (1 L) and then with a mixture of 97:1:2 DCM:TEA:MeOH (1 L) to yield 1-(1-benzylpiperidin-3-yl)-3,6-dihydropyrazolo[4,3-d]pyrrolo[2,3-b]pyridine (0.18 g, 0.54 mmol, 19%) as a brown solid: LC/MS (Table 2, Method a) Rt=1.36 min; MS m/z: 332 (M+H)+.
Reaction SMILES: [N+:1]([C:4]1[CH:18]=[CH:17][C:7]([CH2:8]P(=O)(OCC)OCC)=[CH:6][CH:5]=1)([O-:3])=[O:2].O=[C:20]1[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]1.[H-].[Na+]>O1CCCC1>[N+:1]([C:4]1[CH:5]=[CH:6][C:7]([CH:8]=[C:20]2[CH2:25][CH2:24][N:23]([C:26]([O:28][C:29]([CH3:32])([CH3:31])[CH3:30])=[O:27])[CH2:22][CH2:21]2)=[CH:17][CH:18]=1)([O-:3])=[O:2]
Reactant: CC(C)(C)OC(=O)N1CCC(=O)CC1
Reactant: CCOP(=O)(Cc1ccc([N+](=O)[O-])cc1)OCC
Agent: [H-]
Agent: [Na+]
Solvent: C1CCOC1
Product: CC(C)(C)OC(=O)N1CCC(=Cc2ccc([N+](=O)[O-])cc2)CC1
Temperature: 25 °C
Reaction time: 3 h
Yield: 81.5 %

Procedure:
Diethyl 4-nitrobenzylphosphonate (36 g, 132 mmol) and tert-butyl 4-oxopiperidine-1-carboxylate (26.3 g, 132 mmol) were stirred in tetrahydrofuran (230 mL) and cooled in an ice bath. Sodium hydride was added (6.85 g, 171 mmol) and the reaction was taken off the ice bath and stirred for 3 hours at room temperature. The reaction was quenched with water and extracted with dichloromethane, dried (magnesium sulphate), filtered and evaporated under reduced pressure. The crude material was purified by silica chromatography using a dichloromethane solvent system. The oil obtained was triturated with heptane and filtered to give the title compound as a yellow solid (34.24 g). 1H NMR (CDCl3, 400 MHz): δ 8.18 (d, 2H), 7.33 (d, 2H), 6.40 (s, 1H), 3.54 (t, 2H), 3.43 (t, 2H), 2.46 (t, 2H), 2.38 (t, 2H), 1.48 (s, 9H)
Reaction SMILES: [CH:1]1([CH2:4][NH:5][C:6]2[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[C:8]([C:14]([F:17])([F:16])[F:15])[CH:7]=2)[CH2:3][CH2:2]1.Br[CH2:19][CH2:20][CH2:21][O:22][Si](C(C)(C)C)(C)C>>[CH:1]1([CH2:4][N:5]([CH2:19][CH2:20][CH2:21][OH:22])[C:6]2[CH:13]=[CH:12][C:9]([C:10]#[N:11])=[C:8]([C:14]([F:15])([F:16])[F:17])[CH:7]=2)[CH2:3][CH2:2]1
Reactant: CC(C)(C)[Si](C)(C)OCCCBr
Reactant: N#Cc1ccc(NCC2CC2)cc1C(F)(F)F
Product: N#Cc1ccc(N(CCCO)CC2CC2)cc1C(F)(F)F

Procedure:
Synthesized as described in Example 1B from 4-[(cyclopropylmethyl) amino]-2-(trifluoromethyl)benzonitrile and [(3-bromopropyl)oxy](1,1-dimethylethyl)dimethylsilane: 1H NMR (300 MHz, CD3OD) δ 7.63 (d, J=8.7 Hz, 1H), 7.11 (d, J=2.6 Hz, 1H), 7.02 (dd, J=9.0, 2.7 Hz, 1H), 3.66-3.56 (m, 4H), 3.37 (d, J=6.4 Hz, 2H), 1.83 (tt, J=7.2, 6.2 Hz, 2H), 1.13-0.98 (m, 1H), 0.64-0.53 (m, 2H), 0.37-0.28 (m, 2H); MS (APCI) m/z 299 (M+1).
Reaction SMILES: FC1C=C(C)C=CC=1B(O)O.[F:12][C:13]1[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][C:14]=1[C:20]1[S:24][N:23]=[C:22]([C:25]([F:28])([F:27])[F:26])[C:21]=1[CH2:29][O:30][C:31]1[CH:36]=[CH:35][C:34]([CH2:37][CH2:38][C:39]([O:41]CC)=[O:40])=[C:33]([C:44]([F:47])([F:46])[F:45])[CH:32]=1>>[F:12][C:13]1[CH:18]=[C:17]([CH3:19])[CH:16]=[CH:15][C:14]=1[C:20]1[S:24][N:23]=[C:22]([C:25]([F:28])([F:26])[F:27])[C:21]=1[CH2:29][O:30][C:31]1[CH:36]=[CH:35][C:34]([CH2:37][CH2:38][C:39]([OH:41])=[O:40])=[C:33]([C:44]([F:47])([F:45])[F:46])[CH:32]=1
Reactant: CCOC(=O)CCc1ccc(OCc2c(C(F)(F)F)nsc2-c2ccc(C)cc2F)cc1C(F)(F)F
Agent: Cc1ccc(B(O)O)c(F)c1
Product: Cc1ccc(-c2snc(C(F)(F)F)c2COc2ccc(CCC(=O)O)c(C(F)(F)F)c2)c(F)c1

Procedure:
The title compound was prepared according to the procedure described in Example 172 following Step 1-6 using (2-fluoro-4-methylphenyl)boronic acid for coupling and then hydrolysis of ethyl 3-(4-((5-(2-fluoro-4-methylphenyl)-3-(trifluoromethyl)isothiazol-4-yl)methoxy)-2-(trifluoromethyl)phenyl)propanoate to afford the desired product as an off-white solid. 1H NMR (400 MHz, CD3OD) δ 7.36 (t, J=7.8 Hz, 2H), 7.17 (t, J=7.6 Hz, 2H), 7.00-7.04 (m, 2H), 5.14 (s, 2H), 3.02 (t, J=8.0 Hz, 2H), 2.52 (t, J=7.6 Hz, 2H), 2.44 (s, 3H). Mass spectrum (ESI, m/z): Calcd. for C22H16F7NO3S, 506.1 (M−H). found 506.1.
Reaction SMILES: [F:1][C:2]1[CH:50]=[CH:49][C:5]([C:6]([N:8](C(=O)C2C=CC(F)=CC=2)[C:9]2[N:13]([C@H:14]3[CH2:19][CH2:18][C@@H:17]([C:20](=[O:25])[NH:21][CH:22]([CH3:24])[CH3:23])[CH2:16][CH2:15]3)[C:12]3[CH:26]=[C:27]([O:30][CH2:31][C:32]4[CH:37]=[CH:36][C:35]([O:38][CH3:39])=[CH:34][CH:33]=4)[CH:28]=[CH:29][C:11]=3[N:10]=2)=[O:7])=[CH:4][CH:3]=1.O1CCOCC1.[OH-].[Na+]>CO>[F:1][C:2]1[CH:3]=[CH:4][C:5]([C:6]([NH:8][C:9]2[N:13]([C@H:14]3[CH2:19][CH2:18][C@@H:17]([C:20](=[O:25])[NH:21][CH:22]([CH3:24])[CH3:23])[CH2:16][CH2:15]3)[C:12]3[CH:26]=[C:27]([O:30][CH2:31][C:32]4[CH:33]=[CH:34][C:35]([O:38][CH3:39])=[CH:36][CH:37]=4)[CH:28]=[CH:29][C:11]=3[N:10]=2)=[O:7])=[CH:49][CH:50]=1
Reactant: COc1ccc(COc2ccc3nc(N(C(=O)c4ccc(F)cc4)C(=O)c4ccc(F)cc4)n([C@H]4CC[C@@H](C(=O)NC(C)C)CC4)c3c2)cc1
Agent: [Na+]
Agent: [OH-]
Solvent: C1COCCO1
Solvent: CO
Product: COc1ccc(COc2ccc3nc(NC(=O)c4ccc(F)cc4)n([C@H]4CC[C@@H](C(=O)NC(C)C)CC4)c3c2)cc1
Temperature: 25 °C
Reaction time: 1 h

Procedure:
To a solution of 4-fluoro-N-(4-fluorobenzoyl)-N-(1-(cis-4-(isopropylcarbamoyl)cyclohexyl)-6-(4-methoxybenzyloxy)-1H-benzo[d]imidazol-2-yl)benzamide (442 mg, 0.649 mmol, as a mixture with the mono-acylated material) in MeOH (3.2 mL) and dioxane (3.2 mL) was added a flake of sodium hydroxide (46.7 mg, 1.169 mmol), and the mixture was stirred at RT for 1 hour. The mixture was evaporated and the residue diluted with DCM, washed with 1 N aqueous NaOH, brine, and the organic layer dried over Na2SO4. The residue was purified via flash chromatography using a linear gradient of 0% to 50% EtOAc in hexanes. The title compound was collected as a white solid (275 mg, 76% yield). M/Z calc'd for C32H35FN4O4: 558.65. found 559 [M+H].
Reaction SMILES: Cl.[N:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:9]([C:16]3[CH:17]=[C:18]([CH:22]=[CH:23][CH:24]=3)[C:19](O)=[O:20])=[N:10][N:11]3[CH2:15][CH2:14][S:13][C:12]=23)=[CH:4][CH:3]=1.[C:25]([C:29]1[CH:35]=[CH:34][C:32]([NH2:33])=[CH:31][CH:30]=1)([CH3:28])([CH3:27])[CH3:26]>S(Cl)(Cl)=O.C(OCC)(=O)C>[C:25]([C:29]1[CH:30]=[CH:31][C:32]([NH:33][C:19](=[O:20])[C:18]2[CH:22]=[CH:23][CH:24]=[C:16]([C:9]3[C:8]([C:5]4[CH:6]=[CH:7][N:2]=[CH:3][CH:4]=4)=[C:12]4[S:13][CH2:14][CH2:15][N:11]4[N:10]=3)[CH:17]=2)=[CH:34][CH:35]=1)([CH3:28])([CH3:26])[CH3:27]
Reactant: O=C(O)c1cccc(-c2nn3c(c2-c2ccncc2)SCC3)c1
Reactant: CC(C)(C)c1ccc(N)cc1
Agent: Cl
Solvent: O=S(Cl)Cl
Solvent: CCOC(C)=O
Product: CC(C)(C)c1ccc(NC(=O)c2cccc(-c3nn4c(c3-c3ccncc3)SCC4)c2)cc1
Temperature: 60 °C
Reaction time: 1 h
Yield: 77.4 %

Procedure:
3-(7-Pyridin-4-yl-2,3-dihydro-pyrazolo[5,1-b]thiazol-6-yl)-benzoic acid hydrochloride (45 mg, 0.125 mmol) was dissolved in thionylchloride (1 mL) and stirred at 60° C. for 1 hour. The solvent was distilled and the residue was taken up with toluene, evaporated to dryness and dried under high vacuum for 1 h. The acid chloride was then dissolved in dry pyridine (1 mL) under nitrogen and 4-tert-butylaniline (0.030 mL, 0.187 mmol, 1.5 eq) was added. The mixture was stirred at room temperature for 1 h and then diluted with ethyl acetate and washed with saturated aqueous NaHCO3 and brine. The organic layer was dried over Na2SO4 and concentrated under reduced pressure. The crude product was purified by chromatography on silica gel (eluant DCM/EtOH 95:5 to give 44 mg of N-(4-tert-butyl-phenyl)-3-(7-pyridin-4-yl-2,3-dihydro-pyrazolo[5,1-b]thiazol-6-yl)-benzamide as a white solid (77%).
Reaction SMILES: [NH2:1][CH:2]1[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4][CH2:3]1.C1(C)C=CC(S([N:21]2[C:29]3[C:24](=[C:25]([O:30][CH2:31][CH:32]4[O:34][CH2:33]4)[CH:26]=[CH:27][CH:28]=3)[CH:23]=[CH:22]2)(=O)=O)=CC=1>C(O)C.C(OCC)(=O)C>[CH:2]1([NH:1][CH2:33][CH:32]([OH:34])[CH2:31][O:30][C:25]2[CH:26]=[CH:27][CH:28]=[C:29]3[C:24]=2[CH:23]=[CH:22][NH:21]3)[C:11]2[C:6](=[CH:7][CH:8]=[CH:9][CH:10]=2)[CH2:5][CH2:4][CH2:3]1
Reactant: NC1CCCc2ccccc21
Reactant: Cc1ccc(S(=O)(=O)n2ccc3c(OCC4CO4)cccc32)cc1
Solvent: CCOC(C)=O
Solvent: CCO
Product: OC(CNC1CCCc2ccccc21)COc1cccc2[nH]ccc12
Yield: 12.8 %

Procedure:
A mixture of 1-aminotetralin (5.15 g) and 1-[1-(p-toluenesulfonyl)indol-4-yloxy]-2,3-epoxypropane (12 g) in absolute ethanol (150 ml) is refluxed for 6 hours. The solvent is then evaporated off and the oily residue is dissolved in absolute ethanol (100 ml). A solution of sodium hydroxide (7.5 g) in water (30 ml) is added thereto. The obtained reaction mixture is refluxed for 6 hours and then evaporated under reduced pressure. The residue which is obtained is then dissolved in ethyl acetate (150 ml), the organic solution is thoroughly washed with water, dried over sodium sulfate, and filtered. Ethyl acetate is then evaporated off and the obtained oily residue is chromatographed on a silica gel column eluting with a mixture ethyl acetate/cyclohexane 7/3 v/v. The combined fractions are evaporated to dryness, the oily residue is taken up in a very small amount of ethyl ether which is then removed under vacuum yielding 1.5 g of N-(1,2,3,4-tetrahydronaphth-l-yl)-2-hydroxy-3-(4-indolyloxy)propanamine, as a vitreous solid.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([Cl:12])[C:3]=1[N:13]1[N:17]=[C:16]([CH2:18][CH:19]=O)[C:15]([CH3:21])=[N:14]1.[NH2:22]/[C:23](/[C:28]#[N:29])=[C:24](\[NH2:27])/[C:25]#[N:26]>>[Cl:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[C:4]([Cl:12])[C:3]=1[N:13]1[N:17]=[C:16]([CH2:18][CH:19]=[N:22][C:23]([C:28]#[N:29])=[C:24]([NH2:27])[C:25]#[N:26])[C:15]([CH3:21])=[N:14]1
Reactant: N#C/C(N)=C(/N)C#N
Reactant: Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)nc1CC=O
Product: Cc1nn(-c2c(Cl)cc(C(F)(F)F)cc2Cl)nc1CC=NC(C#N)=C(N)C#N

Procedure:
2-(2,6-Dichloro-4-trifluoromethylphenyl)-5-methyl-2H-1,2,3-triazole-4-acetaldehyde was treated with diaminomaleonitrile in a similar manner to Example 1, to give 2-(2,6-dichloro-4-trifluoromethylphenyl)-4-[2-(2-amino-1,2-dicyanoethenylimino)ethyl]-5-methyl-2H-1,2,3-triazole, which was cyclised in a similar manner to Example 1a, to give 2-(2,6-dichloro-4-trifluoromethylphenyl)-4-[(4,5-dicyano-1H-imidazol-2-yl)methyl]-5-methyl-2H-1,2,3-triazole (Compound 33).
Reaction SMILES: C([O:8][CH2:9][CH:10]([CH2:16][O:17][CH2:18][CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35])[O:11][CH2:12][C:13](=[O:15])[CH3:14])C1C=CC=CC=1.O.C(O)C.CC(C)=O>C(O)(=O)C.[C].[Pd]>[CH2:18]([O:17][CH2:16][CH:10]([O:11][CH2:12][C:13](=[O:15])[CH3:14])[CH2:9][OH:8])[CH2:19][CH2:20][CH2:21][CH2:22][CH2:23][CH2:24][CH2:25][CH2:26][CH2:27][CH2:28][CH2:29][CH2:30][CH2:31][CH2:32][CH2:33][CH2:34][CH3:35]
Reactant: CCCCCCCCCCCCCCCCCCOCC(COCc1ccccc1)OCC(C)=O
Agent: [Pd]
Solvent: CC(=O)O
Solvent: CCO
Solvent: CC(C)=O
Product: CCCCCCCCCCCCCCCCCCOCC(CO)OCC(C)=O
Temperature: 50 °C
Yield: 73.2 %

Procedure:
Hydrogenolysis of 6.5 g (13.3 mmole) of 1-benzyl-3-octadecyl-2-(2-oxopropyl)glycerol was carried out in a mixture of 100 ml of acetic acid, 20 ml of water and 20 ml of ethanol using 2.5 g of 10% palladium carbon (50% wet) at ambient temperature under atmospheric pressure. 100 ml of acetone was added and the mixture was heated up to 50° C. Then, the catalyst was filtered off and 100 ml of 2-methylpropanol was added. Furthermore, the mixture was concentrated to dryness under reduced pressure. 100 ml of toluene was added to the residue and the mixture was again concentrated to dryness. 70 ml of hexane was added to the residue, and the crystals precipitated were collected by filtration to give 3.9 g (yield: 74%) of the above-identified compound.
Reaction SMILES: [NH4+:1].[NH:2]([C:9]1[CH:10]=[CH:11][CH:12]=[C:13]2[C:18]=1[C:17]([S:19]([O-:22])(=[O:21])=[O:20])=[CH:16][CH:15]=[CH:14]2)[C:3]1[CH:8]=[CH:7][CH:6]=[CH:5][CH:4]=1>Cl([O-])(=O)(=O)=O.[Na+]>[CH:8]1[CH:3]=[CH:4][C:5]([NH:1][C:9]2[CH:10]=[CH:11][C:12]([C:12]3[CH:11]=[CH:10][C:9]([NH:2][C:3]4[CH:4]=[CH:5][CH:6]=[CH:7][CH:8]=4)=[C:18]4[C:13]=3[CH:14]=[CH:15][CH:16]=[C:17]4[S:19]([OH:22])(=[O:20])=[O:21])=[C:13]3[CH:14]=[CH:15][CH:16]=[C:17]([S:19]([OH:22])(=[O:20])=[O:21])[C:18]=23)=[CH:6][CH:7]=1
Reactant: [NH4+]
Reactant: O=S(=O)([O-])c1cccc2cccc(Nc3ccccc3)c12
Agent: [Na+]
Agent: [O-][Cl+3]([O-])([O-])[O-]
Product: O=S(=O)(O)c1cccc2c(-c3ccc(Nc4ccccc4)c4c(S(=O)(=O)O)cccc34)ccc(Nc3ccccc3)c12
Reaction time: 2 h
Yield: 30.1 %

Procedure:
A process for the production of bis-(5,5')-8- Anilino -1-naphthalene Sulfonate using an electrochemical cell, consisting of a container (a beaker), a carbon cloth anode, and a metal cathode. The electrochemical cell is charged with ingredients in accord with the following proportions--2.136 g (6.71 mmol) of 8- anilino - 1- naphthalene sulfonic acid ammonium salt dissolved in 100 mL of 0.1 M aqueous sodium perchlorate. As the solution is stirred (A stirring mechanism is used such as a magnetic stirring bar with the container (beaker) supported on a combination heat plate and magnetic drive stirrer), the D.C. power supply voltage is increased until current begins to flow between the electrodes. This solution is electrolyzed for approximately two hours through which time periodic samples are removed and monitored by Hplc (high performance liquid chromatography) until the amount of product reaches a maximum. Thereafter, the solvent is removed and the residue dissolved in a minimal amount of methanol and chromatographed on a short column of neutral alumina using methanol as the eluent. The solvent is removed and the residue dissolved in a minimum amount of water. Excess barium acetate is added to precipitate bis-Ans as barium salt that is collected and dissolved in water. An excess of potassium sulfate is added to convert the barium salt to dipotassium salt. This salt is recrystallized to give 0.686 g (1.01 mmol) of bis - (5,5') - 8 - anilino - 1 - naphthalene sulfonic acid dipotassium salt corresponding to substantially a thirty percent product yield.
Reaction SMILES: [Cl:1][C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[CH2:16][CH2:15][CH2:14][CH2:13][C:12]=2[C:17]([OH:19])=[O:18])=O)=[C:4]([F:20])[CH:3]=1>O1CCOCC1>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([N:8]=[C:9]2[C:11]3[CH2:16][CH2:15][CH2:14][CH2:13][C:12]=3[C:17](=[O:19])[O:18]2)=[C:4]([F:20])[CH:3]=1
Reactant: O=C(O)C1=C(C(=O)Nc2ccc(Cl)cc2F)CCCC1
Solvent: C1COCCO1
Product: O=C1OC(=Nc2ccc(Cl)cc2F)C2=C1CCCC2
Reaction time: 1 h

Procedure:
A solution of 0.4 parts of N,N-dicyclohexylcarbodiimide in 5 parts of dioxane was added at once to a solution of 0.6 parts of 2-(4-chloro-2-fluorophenylaminocarbonyl)-1-cyclohexene-1-carboxylic acid in 5 parts of dioxane to form a slurry. After stirring the slurry for 1 hour, the resulting solid 1,3-dicyclohexylurea was filtered. The filtrate was evaporated under reduced pressure of 300 mm. Hg at 25° C to a yellow, semisolid residue from which 0.27 parts of 3-(4-chloro-2-fluorophenylimino)-4,5,6,7-tetrahydro-1-(3H)-isobenzofuranone melting at 81°-84° C was isolated after fractionation by high pressure liquid chromatography.
Reaction SMILES: [NH:1](C(OCC1C=CC=CC=1)=O)[C@H:2]([C:11]([NH:13][C@@H:14]([C:17]([NH:19][CH2:20][C:21]([NH:23][C@H:24]([C:32]([NH:34][NH:35][C:36]([CH3:38])=[O:37])=[O:33])[CH2:25][C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)=[O:22])=[O:18])[CH2:15][OH:16])=[O:12])[CH2:3][C:4]1[CH:9]=[CH:8][C:7]([OH:10])=[CH:6][CH:5]=1.N(C(OCC1C=CC=CC=1)=O)[C@H](C(N[C@@H](C(NCC(O)=O)=O)[C@H](C)O)=O)CC1C=CC(O)=CC=1>>[NH2:1][C@H:2]([C:11]([NH:13][C@@H:14]([C:17]([NH:19][CH2:20][C:21]([NH:23][C@H:24]([C:32]([NH:34][NH:35][C:36]([CH3:38])=[O:37])=[O:33])[CH2:25][C:26]1[CH:27]=[CH:28][CH:29]=[CH:30][CH:31]=1)=[O:22])=[O:18])[CH2:15][OH:16])=[O:12])[CH2:3][C:4]1[CH:5]=[CH:6][C:7]([OH:10])=[CH:8][CH:9]=1
Reactant: CC(=O)NNC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)[C@@H](CO)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)OCc1ccccc1
Agent: C[C@H](O)[C@@H](NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)OCc1ccccc1)C(=O)NCC(=O)O
Product: CC(=O)NNC(=O)[C@H](Cc1ccccc1)NC(=O)CNC(=O)[C@@H](CO)NC(=O)[C@@H](N)Cc1ccc(O)cc1
Yield: 65.8 %

Procedure:
Using Z-Tyr-(D)-Ser-Gly-Phe-NHNH-COCH3 (0.40 g), the desired compound (0.21 g) is obtained in a similar manner to (II) of Example 4. Rf2 =0.21, [α]D23 +11.4°(c=0.31, MeOH), Amino acid analysis (hydrolized with HCl); Ser 0.85, Gly 1.00, Tyr 0.90, Phe 0.92