Azzindani/Open_Reaction_Data huggingface dataset:
Reaction SMILES: [Si]([O:8][C@@H:9]1[C@@:26]2([CH3:27])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:25]2[CH2:24][CH2:23][C@@:21]2([CH3:22])[C@H:17]3[CH2:18][CH:19]=[C:20]2[CH2:28][O:29][CH2:30][CH2:31][C:32]([OH:35])([CH3:34])[CH3:33])[CH2:12][C@@H:11]([O:36][Si](C(C)(C)C)(C)C)[CH2:10]1)(C(C)(C)C)(C)C.O1CCCC1.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>>[OH:8][C@@H:9]1[C@@:26]2([CH3:27])[C:13](=[CH:14][CH:15]=[C:16]3[C@@H:25]2[CH2:24][CH2:23][C@@:21]2([CH3:22])[C@H:17]3[CH2:18][CH:19]=[C:20]2[CH2:28][O:29][CH2:30][CH2:31][C:32]([OH:35])([CH3:34])[CH3:33])[CH2:12][C@@H:11]([OH:36])[CH2:10]1
Reactant: CC(C)(O)CCOCC1=CC[C@H]2C3=CC=C4C[C@@H](O[Si](C)(C)C(C)(C)C)C[C@H](O[Si](C)(C)C(C)(C)C)[C@]4(C)[C@H]3CC[C@]12C
Agent: CCCC[N+](CCCC)(CCCC)CCCC
Agent: [F-]
Solvent: C1CCOC1
Product: CC(C)(O)CCOCC1=CC[C@H]2C3=CC=C4C[C@@H](O)C[C@H](O)[C@]4(C)[C@H]3CC[C@]12C
Yield: 81.9 %

Procedure:
1α,3β-Bis(tert-butyldimethylsilyloxy)-17-(3-hydroxy-3-methylbutoxymethyl)androsta-5,7,16-triene (40.0 mg, 0.0634 mmol) and a 1M tetra-n-butylammonium fluoride tetrahydrofuran solution (0.4 ml, 0.4 mmol) were subjected to reaction using a procedure similar to that of Example 5(2) (reflux under heating for 1 hour), worked up and the thus obtained residue was purified by preparative thin layer chromatography (dichloromethane:ethanol=10:1, developed once) to give the titled compound (20.9 mg, 82%) as a colorless oil.
Reaction SMILES: [CH2:1]([N:8]([CH:40]1[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1)[C:9](=[O:39])[C:10]1[CH:15]=[C:14]([N:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][CH:24]([C:31]3[CH:36]=[CH:35][CH:34]=[CH:33][CH:32]=3)[C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[CH2:18][CH2:17]2)[CH:13]=[CH:12][C:11]=1[O:37]C)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.B(Br)(Br)Br.O.C(=O)([O-])O.[Na+]>ClCCl>[CH2:1]([N:8]([CH:40]1[CH2:45][CH2:44][CH2:43][CH2:42][CH2:41]1)[C:9](=[O:39])[C:10]1[CH:15]=[C:14]([N:16]2[CH2:21][CH2:20][N:19]([CH2:22][CH2:23][CH:24]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:31]3[CH:32]=[CH:33][CH:34]=[CH:35][CH:36]=3)[CH2:18][CH2:17]2)[CH:13]=[CH:12][C:11]=1[OH:37])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1
Reactant: COc1ccc(N2CCN(CCC(c3ccccc3)c3ccccc3)CC2)cc1C(=O)N(Cc1ccccc1)C1CCCCC1
Agent: BrB(Br)Br
Agent: O=C([O-])O
Agent: [Na+]
Solvent: O
Solvent: ClCCl
Product: O=C(c1cc(N2CCN(CCC(c3ccccc3)c3ccccc3)CC2)ccc1O)N(Cc1ccccc1)C1CCCCC1
Temperature: 0 °C
Reaction time: 0.33 h
Yield: 77.9 %

Procedure:
The compound (46 mg) prepared in Example 70 was dissolved in dichloromethane (3.8 ml). A 1 M solution (0.23 ml) of boron tribromide in dichloromethane was added to the solution at 0° C. The mixture was stirred at 0° C. for 20 min, and was then stirred at room temperature for 30 min. Water and a saturated aqueous sodium hydrogencarbonate solution were added to the reaction solution, and the mixture was extracted with dichloromethane, followed by washing with saturated brine. The organic layer was dried over anhydrous magnesium sulfate. The solvent was then removed by distillation under the reduced pressure. The residue was developed by preparative TLC (chloroform:methanol=20:1) to give the title compound (35 mg).
Reaction SMILES: [N:1]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:2]=1[C:3]([O:5][C:6]2=[O:11])=O.N1C2C(=CC=CC=2)C=C1.[Cl-].[Ca+2].[Cl-].[Cl-].[Al+3].[Cl-].[Cl-].C(OC(=O)C)(=O)C.N>C(O)(=O)C.C(#N)C.[Cl-].[Zn+2].[Cl-].[Fe](Cl)Cl.[Co](Cl)Cl.[Cu](Cl)Cl>[C:6]1([C:7]2[C:2](=[N:1][CH:10]=[CH:9][CH:8]=2)[CH2:3][O:5]1)=[O:11]
Reactant: O=C1OC(=O)c2ncccc21
Agent: Cl[Co]Cl
Agent: Cl[Cu]Cl
Agent: Cl[Fe]Cl
Solvent: CC(=O)OC(C)=O
Solvent: CC#N
Solvent: CC(=O)O
Product: O=C1OCc2ncccc21
Temperature: 25 °C

Procedure:
A particularly advantageous embodiment of the novel process comprises dissolving or suspending quinolinic anhydride in a saturated aliphatic C2 -C4 -monocarboxylic acid, in particular acetic acid, or also in acetonitrile, adding an indole compound of the formula (7a) and stirring the mixture at room temperature in the presence of an inorganic metal salt, in particular a metal halide, of a polyvalent metal or atomic weight 26 to 66, for example zinc chloride, calcium chloride, aluminium chloride, iron chloride, cobalt chloride or copper dichloride, preferably for 2 to 6 hours. The compound of the formula (5a) is then added and, after addition of acetic anhydride, the reaction mixture is heated at 30° to 60° C., preferably for 1 to 3 hours. The pH is then adjusted to 7.5 to 9 for example with an alkali metal hydroxide or aqueous ammonia. The precipitated 4-azaphthalide compound of the formula (1a) is isolated and, if necessary, recrystallised.
Reaction SMILES: [C:1]1([CH:7]([C:10]2[CH:15]=[CH:14][CH:13]=[CH:12][CH:11]=2)[CH2:8][OH:9])[CH:6]=[CH:5][CH:4]=[CH:3][CH:2]=1.[C:16](Cl)([Cl:18])=[O:17]>C1(C)C=CC=CC=1>[Cl:18][C:16]([O:9][CH2:8][CH:7]([C:1]1[CH:2]=[CH:3][CH:4]=[CH:5][CH:6]=1)[C:10]1[CH:11]=[CH:12][CH:13]=[CH:14][CH:15]=1)=[O:17]
Reactant: O=C(Cl)Cl
Reactant: OCC(c1ccccc1)c1ccccc1
Solvent: Cc1ccccc1
Product: O=C(Cl)OCC(c1ccccc1)c1ccccc1
Temperature: 0 °C
Reaction time: 0.5 h
Yield: 80 %

Procedure:
To a solution of 7.0 g (35.4 mmol) of the alcohol (12) in 50 mL toluene at 0 degrees C., was slowly added 100 mL phosgene in toluene (12.5% phosgene in toluene). The reaction mixture was stirred at 0 degrees C. for 30 minutes and then at room temperature for 2 hours. The excess reagent and solvent was removed under reduced pressure and the crude product was quickly passed through a pad of silica gel (silica gel, CH2Cl2 -Hexane 2:3) to yield 7.8 g (80%) of the chloroformate (13). DCI-NH3 -MS, m/z (relative intensity), 259 (M+, 55); 1H-NMR (CDCl3, 300 MHz) 7.28 (m, 10H), 4.83 (d, 2H, J=7.5 Hz), and 4.45 (t, 1H, J=7.5 Hz).
Reaction SMILES: [NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][CH2:11][CH2:12][NH:13][CH2:14][CH2:15][O:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([N+:23]([O-])=O)[C:18]=2[NH2:26])=[CH:2]1>C(O)C.[Pd]>[NH:1]1[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]([CH2:10][CH2:11][CH2:12][NH:13][CH2:14][CH2:15][O:16][C:17]2[CH:22]=[CH:21][CH:20]=[C:19]([NH2:23])[C:18]=2[NH2:26])=[CH:2]1
Reactant: Nc1c(OCCNCCCc2c[nH]c3ccccc23)cccc1[N+](=O)[O-]
Agent: [Pd]
Solvent: CCO
Product: Nc1cccc(OCCNCCCc2c[nH]c3ccccc23)c1N
Reaction time: 4 h
Yield: 89.8 %

Procedure:
To a solution of the 2-{2-[3-(1H-indol-3-yl)-propylamino]-ethoxy}-6-nitro-phenylamine (1.9 g, 5.39 mmol) in ethanol (40 ml) was added 5% palladium on carbon (0.5 g) under nitrogen. The resulting slurry was hydrogenated under 40 psi for 4 hours. The catalyst was removed by filtration and the ethanol evaporated to afford the crude product. Purification by chromatography (3-10% 2N ammonia methanol in methylene chloride) gave 1.57 g (90.6%) of product as a brown oil. 1H NMR (400 MHZ, DMSO-d6), δ1.79, (2H, q, J=7.2 Hz); 2.62, (2H, t, J=7.1 Hz); 2.71, (2H, t, J=7.2 Hz); 2.83, (2H, t, J=5.2 Hz); 4.09, (2H, br); 4.43, (2H, br); 6.19, (1H, t, J=8.0 Hz); 6.33, (1H, t, J=7.9 Hz); 6.94; (1H, t, J=7.0 Hz); 7.03, (1H, t, J=7.2 Hz); 7.08, (1H, d, J=2.0 Hz); 7.29, (2H, d, J=7.4 Hz); 7.31, (2H, d, J=7.4 Hz); 10.7, (1H, br).
Reaction SMILES: [NH2:1][C:2]1[CH:3]=[C:4]([C:8]([Cl:19])=[CH:9][C:10]=1[C:11](=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1)[C:5]([OH:7])=[O:6].Cl[Si](C)(C)C.N1C=CC=CC=1.[C:31]1([CH2:44][O:45][C:46](Cl)=[O:47])[C:43]2[CH2:42][C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[C:35]=2[CH:34]=[CH:33][CH:32]=1>C(Cl)Cl.C(OCC)(=O)C.CCCCCC.C(O)(=O)C.C(OCC)(=O)C>[C:11]([C:10]1[CH:9]=[C:8]([Cl:19])[C:4]([C:5]([OH:7])=[O:6])=[CH:3][C:2]=1[NH:1][C:46]([O:45][CH2:44][C:31]1[C:43]2[CH2:42][C:41]3[C:36](=[CH:37][CH:38]=[CH:39][CH:40]=3)[C:35]=2[CH:34]=[CH:33][CH:32]=1)=[O:47])(=[O:18])[C:12]1[CH:17]=[CH:16][CH:15]=[CH:14][CH:13]=1
Reactant: O=C(Cl)OCc1cccc2c1Cc1ccccc1-2
Reactant: Nc1cc(C(=O)O)c(Cl)cc1C(=O)c1ccccc1
Agent: C[Si](C)(C)Cl
Solvent: CCOC(C)=O
Solvent: CC(=O)O
Solvent: ClCCl
Product: O=C(Nc1cc(C(=O)O)c(Cl)cc1C(=O)c1ccccc1)OCc1cccc2c1Cc1ccccc1-2
Temperature: 0 °C
Reaction time: 1 h
Yield: 64 %

Procedure:
A solution was prepared by diluting 3-amino-4-benzoyl-6-chlorobenzoic acid (5.59 g, 20.3 mmol) with approximately 70 mL of CH2Cl2. Chlorotrimethylsilane (5.50 g, 51 mmol, 2.5 equivalents) was added by syringe and the resulting white slurry was heated at gentle reflux for 1.5 hours. After cooling the mixture to 0° C., pyridine (3.69 g, 46.7 mmol, 2.3 equivalents) was added by syringe, immediately followed by addition of fluorenylmethoxycarbonyl chloride (5.78 g, 22.3 mmol, 1.1 equivalents). The resulting slurry was stirred for one hour under a nitrogen atmosphere. The reaction solution was then diluted with CH2Cl2 (150 mL) and was extracted three times with 1.0N aqueous sodium bisulfate (100 mL) and once with aqueous sodium chloride (100 mL), then dried over sodium sulfate and concentrated in vacuo to give a viscous oil. Pure product was obtained in 64% yield (6.50 g) as a white solid by flash chromatography with 5 cm×25 cm silica gel and 40:60 ethyl acetate and then 75:25:1 ethyl acetate/hexane/acetic acid as the eluent. The structure was confirmed by proton NMR, carbon-13NMR, and FAB mass spectroscopy.
Reaction SMILES: [H-].[Al+3].[Li+].[H-].[H-].[H-].[N:7]1([CH2:12][CH2:13][O:14][C:15]2[CH:23]=[CH:22][C:18]([C:19]([NH2:21])=O)=[CH:17][CH:16]=2)[CH2:11][CH2:10][CH2:9][CH2:8]1>C1COCC1>[N:7]1([CH2:12][CH2:13][O:14][C:15]2[CH:16]=[CH:17][C:18]([CH2:19][NH2:21])=[CH:22][CH:23]=2)[CH2:8][CH2:9][CH2:10][CH2:11]1
Reactant: NC(=O)c1ccc(OCCN2CCCC2)cc1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Product: NCc1ccc(OCCN2CCCC2)cc1
Temperature: 25 °C
Reaction time: 0.5 h
Yield: 101.7 %

Procedure:
Lithium aluminum hydride (132 mg, 3.49 mmol, 2.1 eq.) was added to a solution of 4-[2-(1-pyrrolidinyl)ethoxy]benzamide (389 mg, 1.66 mmol) in dry THF (25 mL) then the reaction heated at reflux for 20 h. The reaction was allowed to cool to ambient temperature then quenched with water (0.250 mL). Aqueous sodium hydroxide (0.250 mL of 15% w/v) then water (0.750 mL) was added and the reaction stirred for 30 min. The reaction mixture was passed through a pad of diatomaceous earth which was washed with THF (3×15 mL). The combined organics were concentrated under reduced pressure to give the amine as oil (372 mg, >100%) which was used without further purification.
Reaction SMILES: [Cl:1][C:2]1[CH:3]=[CH:4][C:5]([C:11]([F:14])([F:13])[F:12])=[C:6](B(O)O)[CH:7]=1.FC(F)(F)S(O[C:21]1[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH:22]=1)(=O)=O.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>O.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:3]=[CH:4][C:5]([C:11]([F:14])([F:13])[F:12])=[C:6]([C:21]2[CH2:26][CH2:25][N:24]([C:27]([O:29][C:30]([CH3:33])([CH3:32])[CH3:31])=[O:28])[CH2:23][CH:22]=2)[CH:7]=1
Reactant: CC(C)(C)OC(=O)N1CC=C(OS(=O)(=O)C(F)(F)F)CC1
Reactant: OB(O)c1cc(Cl)ccc1C(F)(F)F
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: O
Solvent: COCCOC
Product: CC(C)(C)OC(=O)N1CC=C(c2cc(Cl)ccc2C(F)(F)F)CC1
Temperature: 80 °C
Yield: 84 %

Procedure:
A mixture of (5-chloro-2-(trifluoromethyl)phenyl)boronic acid (0.453 g, 2.02 mmol), tert-butyl 4-(((trifluoromethyl)sulfonyl)oxy)-5,6-dihydropyridine-1(2H)-carboxylate (0.669 g, 2.02 mmol), tetrakis(triphenylphosphine)palladium (0.117 g, 0.1 mmol), sodium carbonate (2 M, 5 mL), and 1,2-dimethoxyethane (10 mL) was heated at 80° C. under microwave irradiation for 1.5 h. After cooling to ambient temperature, the mixture was diluted with water (80 mL) and extracted with ethyl acetate (80 mL). The extract was washed with brine (2×50 mL), dried over Na2SO4, filtered, and concentrated under reduced pressure. The resulting residue was chromatographed over silica gel (0-25% EtOAc in hexanes) to give tert-butyl 4-(5-chloro-2-(trifluoromethyl)phenyl)-5,6-dihydropyridine-1(2H)-carboxylate as colorless oil (0.614 g, 84%): 1H NMR (300 MHz, CDCl3) δ 7.59 (d, J=8.5 Hz, 1H), 7.37-7.22 (m, 1H), 7.22 (d, J=1.68 Hz, 1H), 5.60 (br, 1H), 4.02 (br, 2H), 3.61 (br, 2H), 2.34 (br, 2H), 1.50 (s, 9H); MS (ESI+) m/z 306 [M+H]+.
Reaction SMILES: [CH2:1]([OH:10])[C@H:2]([C@@H:4]([C@@H:6]([CH2:8][OH:9])[OH:7])[OH:5])[OH:3].[OH-].[Na+].[H][H]>[Ni]>[CH2:8]([OH:9])[CH:6]([OH:7])[CH:4]([OH:5])[CH:2]([OH:3])[CH2:1][OH:10]
Reactant: OC[C@@H](O)C(O)[C@H](O)CO
Reactant: [H][H]
Agent: [Ni]
Agent: [Na+]
Agent: [OH-]
Product: OCC(O)C(O)C(O)CO
Reaction time: 4 h

Procedure:
Fermentation of glucose to arabinitol is performed by using a culture medium of 10% (w/v) glucose, 0.5% (w/v) yeast extract and 0.1% (w/v) urea. The medium is inoculated with a yeast strain of the genus Endomycopsis chodati. After 72 hours fermentation time 56% arabinitol was obtained without considerable amounts of glycerol (below 4%). After demineralisation and refining the arabinitol syrup is directly used for polyol isomerisation in the presence of Raney-nickel (5% catalyst slurry on total dry substance). The pH is increased to 11, by the addition of 0.5 M NaOH. A hydrogen pressure of 4 MPa is applied at a temperature of 170° C. and the isomerisation reaction is stopped after 4 hours, resulting in a pentitol mixture of the following composition: arabinitol (90%), xylitol (6%), ribitol (4%).
Reaction SMILES: [NH2:1][C:2]1[CH:10]=[CH:9][C:8]([CH3:11])=[CH:7][C:3]=1[C:4]([NH2:6])=O.[H-].[H-].[H-].[H-].[Li+].[Al+3].O.[OH-].[Na+]>C1COCC1>[NH2:6][CH2:4][C:3]1[CH:7]=[C:8]([CH3:11])[CH:9]=[CH:10][C:2]=1[NH2:1]
Reactant: Cc1ccc(N)c(C(N)=O)c1
Agent: [Al+3]
Agent: [H-]
Agent: [Li+]
Solvent: C1CCOC1
Solvent: O
Product: Cc1ccc(N)c(CN)c1
Temperature: 0 °C
Yield: 6.4 %

Procedure:
Under an atmosphere of argon, a solution 2-amino-5-methylbenzamide (1.2 g, 80 mmol) in THF (25 ml) was added to a suspension of LiAlH4 (1.54 g, 40 mmol) in THF (25 ml) over 20 min. The suspension was heated to reflux (4 h). For workup, the mixture was cooled to 0° C., and 1.5 ml H2O, 3 ml 4n NaOH, and 3 ml H2O were added subsequently. The suspension was dried (Na2SO4), and evaporated under reduced pressure. The title compound (700 mg, 63%) was isolated from the residue by chromatographic purification (silica gel, CH2Cl2/MeOH (2M NH3)=9:1).
Reaction SMILES: [CH:1]1[C:11]2[CH:10]=[CH:9][C:8]3[CH:12]=[CH:13][CH:14]=[CH:15][C:7]=3[CH:6]([C:16]3[C:17](=[S:34])[NH:18][C:19](=[O:33])[N:20]([CH2:22][C:23]4[S:24][CH:25]=[C:26]([C:28]([O:30]CC)=[O:29])[N:27]=4)[CH:21]=3)[C:5]=2[CH:4]=[CH:3][CH:2]=1.O.[OH-].[Li+]>CO.O>[CH:12]1[C:8]2[CH:9]=[CH:10][C:11]3[CH:1]=[CH:2][CH:3]=[CH:4][C:5]=3[CH:6]([C:16]3[C:17](=[S:34])[NH:18][C:19](=[O:33])[N:20]([CH2:22][C:23]4[S:24][CH:25]=[C:26]([C:28]([OH:30])=[O:29])[N:27]=4)[CH:21]=3)[C:7]=2[CH:15]=[CH:14][CH:13]=1
Reactant: CCOC(=O)c1csc(Cn2cc(C3c4ccccc4C=Cc4ccccc43)c(=S)[nH]c2=O)n1
Agent: [Li+]
Agent: [OH-]
Solvent: O
Solvent: CO
Product: O=C(O)c1csc(Cn2cc(C3c4ccccc4C=Cc4ccccc43)c(=S)[nH]c2=O)n1
Temperature: 25 °C
Reaction time: 8 h

Procedure:
A mixture of the product of step (v) (1.5 g) and lithium hydroxide monohydrate (1.26 g) in methanol (100 ml) and water (50 ml) was stirred at room temperature overnight. The solution was concentrated under reduced pressure to 50 ml and the pH adjusted to 3.5 with 2M hydrochloric acid. The precipitated product was collected, washed with water and dried. Yield 1.1 g.
Reaction SMILES: [F:1][C:2]([F:39])([F:38])[C:3]1[CH:4]=[C:5]([CH:31]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:33]=1)[CH2:6][N:7]1[CH2:14][CH2:13][CH2:12][NH:11][C:10]2[N:15]=[C:16](S(C)(=O)=O)[N:17]=[C:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[CH3:25])[C:9]=2[C:8]1=[O:30].[Na].[NH:41]1[CH:45]=[CH:44][N:43]=[CH:42]1>>[F:1][C:2]([F:39])([F:38])[C:3]1[CH:4]=[C:5]([CH:31]=[C:32]([C:34]([F:37])([F:36])[F:35])[CH:33]=1)[CH2:6][N:7]1[CH2:14][CH2:13][CH2:12][NH:11][C:10]2[N:15]=[C:16]([N:41]3[CH:45]=[CH:44][N:43]=[CH:42]3)[N:17]=[C:18]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][C:20]=3[CH3:25])[C:9]=2[C:8]1=[O:30]
Reactant: c1c[nH]cn1
Reactant: Cc1ccccc1-c1nc(S(C)(=O)=O)nc2c1C(=O)N(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)CCCN2
Agent: [Na]
Product: Cc1ccccc1-c1nc(-n2ccnc2)nc2c1C(=O)N(Cc1cc(C(F)(F)F)cc(C(F)(F)F)c1)CCCN2
Yield: 72.5 %

Procedure:
In a similar manner to Example 1, 6-[3,5-bis(trifluoromethyl)benzyl]-5,6,7,8,9,10-hexahydro-4-(2-methylphenyl)-2-(methylsulfonyl)-5-oxopyrimido[4,5-b][1,5]diazocine (Compound of Reference Example 19; 85.9 mg) was reacted with sodium salt of imidazole (16.2 mg) to obtain 6-[3,5-bis(trifluoromethyl)benzyl]-5,6,7,8,9,10-hexahydro-2-(imidazole-1-yl)-4-(2-methylphenyl)-5-oxopyrimido[4,5-b][1,5]diazocine (61.0 mg, 73%).
Reaction SMILES: [F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:21]=3Br)[C@H:14]2[CH3:28])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1.[CH3:31][O:32][C:33]1[CH:38]=[CH:37][C:36]([C:39]2[CH:44]=[CH:43][C:42]([C:45]([O:47][CH3:48])=[O:46])=[CH:41][C:40]=2[CH3:49])=[CH:35][C:34]=1B1OC(C)(C)C(C)(C)O1.C(=O)([O-])[O-].[Na+].[Na+].CCOC(C)=O>O.CCO.C1(C)C=CC=CC=1.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.CCCCCC>[F:1][C:2]([F:30])([F:29])[C:3]1[CH:4]=[C:5]([C@H:13]2[O:17][C:16](=[O:18])[N:15]([CH2:19][C:20]3[CH:25]=[C:24]([Cl:26])[CH:23]=[CH:22][C:21]=3[C:34]3[CH:35]=[C:36]([C:39]4[CH:44]=[CH:43][C:42]([C:45]([O:47][CH3:48])=[O:46])=[CH:41][C:40]=4[CH3:49])[CH:37]=[CH:38][C:33]=3[O:32][CH3:31])[C@H:14]2[CH3:28])[CH:6]=[C:7]([C:9]([F:12])([F:11])[F:10])[CH:8]=1
Reactant: C[C@H]1[C@@H](c2cc(C(F)(F)F)cc(C(F)(F)F)c2)OC(=O)N1Cc1cc(Cl)ccc1Br
Reactant: COC(=O)c1ccc(-c2ccc(OC)c(B3OC(C)(C)C(C)(C)O3)c2)c(C)c1
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: CCCCCC
Solvent: Cc1ccccc1
Product: COC(=O)c1ccc(-c2ccc(OC)c(-c3ccc(Cl)cc3CN3C(=O)O[C@H](c4cc(C(F)(F)F)cc(C(F)(F)F)c4)[C@@H]3C)c2)c(C)c1

Procedure:
A mixture of the title compound from Step B (0.068 g, 0.13 mmol), methyl 4′-methoxy-2-methyl-3′-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)biphenyl-4-carboxylate (INTERMEDIATE 11) (0.075 g, 0.19 mmol), tetrakis(triphenylphosphine)palladium (15 mg, 5% mol) and sodium carbonate (0.07 g, 0.65 mmol) in 7 ml of water/EtOH/toluene (1:2:4) was heated to reflux for 5 h. TLC (EtOAc:hexane/1:3) showed that the reaction was over. The solvents were removed. Water (10 ml) was added. The organic was extracted with methylene chloride (3×20 ml). The combined methylene chloride layers were washed with brine, and dried over sodium sulfate. The title compound was obtained after purification with preparative TLC using 10% EtOAc in hexane as the eluant. 1H NMR (CDCl3, 500 MHz): δ 1:1 mixture of atropisomers 7.96 (d, J=9 Hz, 1H), 7.88(m, 2H), 7.72(s, 1H), 7.65(s, 1H), 7.49 (d, J=2 Hz, 0.5H), 7.39 (m, 2H), 7.36 (d, J=2 Hz, 0.5H), 7.24-7.28 (m, 2H), 7.15 (m, 1H), 7.70 (m, 1H), 5.62 (d, J=8 Hz, 0.5H), 5.52(d, J=8 Hz, 0.5H), 4.91(t, J=16 Hz, 1H), 4.08(d, J=15.5 Hz, 0.5H), 3.95(s, 3H), 3.88 (s, 3H), 3.87(d, J=16 Hz, 0.5H), 3.84 (m, 1H), 2.39(s, 1.5H), 2.33(s, 1.5H), 0.56(d, J=7 Hz, 1.5H), 0.43(d, J=6.5 Hz, 1.5H).
Reaction SMILES: [C:1]([CH2:3][CH2:4][CH:5]1[CH2:10][CH2:9][CH2:8][CH2:7][C:6]1=O)#[N:2].N.[H][H]>>[NH:2]1[CH:10]2[CH:5]([CH2:6][CH2:7][CH2:8][CH2:9]2)[CH2:4][CH2:3][CH2:1]1
Reactant: N#CCCC1CCCCC1=O
Reactant: [H][H]
Agent: N
Product: C1CCC2NCCCC2C1
Yield: 67.5 %

Procedure:
Through a tubular reactor (diameter 16 mm, packing height 50 cm, oil-heated double jacket), installed up-stream of the hydrogenation reactor and packed with 64.4 g (92 ml) of γ-aluminum oxide there were passed upwardly, per hour, 55.4 g of 2-(2-cyanoethyl)-cyclohexanone (purity 96%, 0.352 mole) and 875 ml of liquid ammonia (525 g, 30.9 moles) at a pressure of 250 bar and a temperature of 70° C. Hydrogen was then added to the stream at a rate of 200 standard liters (8.9 moles) per hour, and the effluent from the in-line imination reactor was passed upwardly through the hydrogenation reactor at a pressure of 250 bar and a temperature of 120° C. After an on-stream of 3.5 hours the separation and distillation measures as per Example 2 had yielded, besides 33.1 g of decahydroquinoline, 138.8 of 2-(3-aminopropyl)-cyclohexylamine, this corresponding to a yield of 2-(3-aminopropyl)-cyclohexylamine of 71.5% of theory.
Reaction SMILES: [F:1][C:2]1[C:7]([N:8]2[CH2:13][CH2:12][NH:11][CH2:10][CH2:9]2)=[CH:6][C:5]([NH2:14])=[C:4]([NH2:15])[CH:3]=1.[C:16](=S)=[S:17].[OH-].[K+].[K+].[Br-]>O.C(O)C>[F:1][C:2]1[C:7]([N:8]2[CH2:9][CH2:10][NH:11][CH2:12][CH2:13]2)=[CH:6][C:5]2[N:14]=[C:16]([SH:17])[NH:15][C:4]=2[CH:3]=1
Reactant: Nc1cc(F)c(N2CCNCC2)cc1N
Reactant: S=C=S
Agent: [Br-]
Agent: [K+]
Agent: [OH-]
Solvent: CCO
Solvent: O
Product: Fc1cc2[nH]c(S)nc2cc1N1CCNCC1
Yield: 81.2 %

Procedure:
6-Fluoro-5-(piperazin-1-yl)-2-mercapto-1H-benzimidazole (4.3 g, 80%) was prepared by an analogous procedure as described in preparation 1 (step 5) using the diamine (4.5 g, 0.021 mol) (obtained in step 2 above), carbon disulfide (1.9 g, 0.025 mol), potassium hydroxide (1.4 g, 0.025 mol), ethanol (25 mL) and water (5 mL). mp 100-10 1 ° C.; IR (KBr) 3133, 1482 cm-1 ; 1H NMR (DMSO-d6) δ 2.25 (s, 1H, SH), 2.90 (m, 4H, N(CH2)2), 4.10 (brs, 1H, NH), 4.48 (m, 4H, N(CH2)2), 6.80 (d, J=8.4 Hz, 1H), 7.00 (d, J=12.3 Hz, 1H), 12.30 (brs, 1H, NH); Mass (m/z) 252 (M+.).
Reaction SMILES: C([O:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]=[C:14]([CH2:19][N:20]1[CH:24]=[C:23]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:22](/[CH:31]=[CH:32]/[C:33]([O:35][CH2:36][CH3:37])=[O:34])=[CH:21]1)[CH:13]=[CH:12]2)C1C=CC=CC=1.C(O)C>[C].[Pd].O1CCCC1>[OH:8][C:9]1[CH:10]=[C:11]2[C:16](=[CH:17][CH:18]=1)[CH:15]=[C:14]([CH2:19][N:20]1[CH:24]=[C:23]([C:25]3[CH:30]=[CH:29][CH:28]=[CH:27][CH:26]=3)[C:22]([CH2:31][CH2:32][C:33]([O:35][CH2:36][CH3:37])=[O:34])=[CH:21]1)[CH:13]=[CH:12]2
Reactant: CCOC(=O)/C=C/c1cn(Cc2ccc3cc(OCc4ccccc4)ccc3c2)cc1-c1ccccc1
Agent: [Pd]
Solvent: CCO
Solvent: C1CCOC1
Product: CCOC(=O)CCc1cn(Cc2ccc3cc(O)ccc3c2)cc1-c1ccccc1
Temperature: 25 °C
Reaction time: 4 h
Yield: 90.3 %

Procedure:
A mixture of ethyl(E)-3-[1-(6-benzyloxy-2-naphthylmethyl)-4-phenyl-3-pyrrolyl]propenoate (1.46 g), 5% palladium-carbon (1.5 g), ethanol (15 ml), and tetrahydrofuran (15 ml) was stirred for 4 hours at room temperature under a hydrogen atmosphere. After the palladium-carbon was removed by filtration, the filtrate was concentrated. The residue was subjected to silica gel column chromatography, and ethyl 3-[1-(6-hydroxy-2-naphthylmethyl)-4-phenyl-3-pyrrolyl]propionate (1.08 g, yield: 90%) was obtained as an oily substance from the fraction eluted with ethyl acetate-hexane (1:1, volume ratio).