cyclohexylhydrazine

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:135.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methanesulfonic acid 5bromo-2-propionyl-phenyl ester (36.6 g, 119 mmol) was combined with cyclohexylhydrazine (27.2 g, 238 mmol) and ammonium acetate (23.0 g, 299 mmol) in xylenes (220 mL). The reaction mixture was heated to 135° C. in a Dean-Stark apparatus for 48 hours. The reaction was cooled to room temperature and concentrated to a low volume under reduced pressure. The crude product was filtered through a pad of silica gel (weight ratio product/silica gel 1/5) eluting first with hexanes then with a 10/90 mixture of ethyl acetate and hexanes. The fractions containing principally 6-bromo-1-cyclohexyl-3-ethyl-1H-indazole were collected. A second crop was obtained by repeating the above silica treatment with the mixed fractions. The two crops were combined and dried under vacuum to yield 28.0 g of 6-bromo-1-cyclohexyl-3-ethyl-1H-indazole (76% yield). 1H NMR (400 MHz, CDCl3) δ 1.35 (t, 3, J=7.7), 1.39-2.06 (m, 10), 2.95 (q, 2, J=7.7), 4.21-4.28(m, 1), 7.15 (d, 1, J=8.5), 7.51 (d, 1, J=8.5), 7.56 (s, 1). 13C NMR (100 MHz, CDCl3) δ 13.95, 20.50, 25.35, 25.84, 32.44, 58.15, 112.01, 120.10, 121.37, 121.65, 122.82, 140.37, 146.60. IR 2934, 2855, 1606, 1502, 1451, 1048, 951, 834 cm-1. Analysis calculated for C15H19BrN2 : C, 58.64; H, 6.23; N, 9.12. Found: C, 58.82; H, 6.20; N, 9.01. The reaction was cooled to room temperature concentrated to a low volume under reduced pressure The crude product was filtered through a pad of silica gel (weight ratio product/silica gel 1/5) eluting first with hexanes with a 10/90 mixture of ethyl acetate and hexanes The fractions containing principally 6-bromo-1-cyclohexyl-3-ethyl-1H-indazole were collected A second crop was obtained dried under vacuum

Conditions: temp:135.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Methanesulfonic acid 5bromo-2-propionyl-phenyl ester (36.6 g, 119 mmol) was combined with cyclohexylhydrazine (27.2 g, 238 mmol) and ammonium acetate (23.0 g, 299 mmol) in xylenes (220 mL). The reaction mixture was heated to 135° C. in a Dean-Stark apparatus for 48 hours. The reaction was cooled to room temperature and concentrated to a low volume under reduced pressure. The crude product was filtered through a pad of silica gel (weight ratio product/silica gel 1/5) eluting first with hexanes then with a 10/90 mixture of ethyl acetate and hexanes. The fractions containing principally 6-bromo-1-cyclohexyl-3-ethyl-1H-indazole were collected. A second crop was obtained by repeating the above silica treatment with the mixed fractions. The two crops were combined and dried under vacuum to yield 28.0 g of 6-bromo-1-cyclohexyl-3-ethyl-1H-indazole (76% yield). 1H NMR (400 MHz, CDCl3) δ 1.35 (t, 3, J=7.7), 1.39-2.06 (m, 10), 2.95 (q, 2, J=7.7), 4.21-4.28(m, 1), 7.15 (d, 1, J=8.5), 7.51 (d, 1, J=8.5), 7.56 (s, 1). 13C NMR (100 MHz, CDCl3) δ 13.95, 20.50, 25.35, 25.84, 32.44, 58.15, 112.01, 120.10, 121.37, 121.65, 122.82, 140.37, 146.60. IR 2934, 2855, 1606, 1502, 1451, 1048, 951, 834 cm-1. Analysis calculated for C15H19BrN2 : C, 58.64; H, 6.23; N, 9.12. Found: C, 58.82; H, 6.20; N, 9.01. The reaction was cooled to room temperature concentrated to a low volume under reduced pressure The crude product was filtered through a pad of silica gel (weight ratio product/silica gel 1/5) eluting first with hexanes with a 10/90 mixture of ethyl acetate and hexanes The fractions containing principally 6-bromo-1-cyclohexyl-3-ethyl-1H-indazole were collected A second crop was obtained dried under vacuum

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Starting from 1,3-dihydro-5-(3,6-dihydro-6-methyl-2-oxo -2H-1,3,4-thiadiazin-5-yl)-3-phenylimino-2H-indol-2-one, and cyclohexylhydrazine and following the method described in Example 21, the desired compound was obtained.

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (52 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 1.5 hr. Next, cyclohexylhydrazine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 7 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (10 mg, yield 13%). the mixture was further stirred at room temperature for 7 hr by washing with water and saturated brine in that order The organic layer was then dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure the residue was purified by HPLC

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,5-dimethylaniline (52 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 1.5 hr. Next, cyclohexylhydrazine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 7 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (10 mg, yield 13%). the mixture was further stirred at room temperature for 7 hr by washing with water and saturated brine in that order The organic layer was then dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure the residue was purified by HPLC

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 7 hr. Next, cyclohexylhydrazine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 12 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (8 mg, yield 10%). the mixture was further stirred at room temperature for 12 hr by washing with water and saturated brine in that order The organic layer was then dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure the residue was purified by HPLC

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 4-[(6,7-Dimethoxy-4-quinolyl)oxy]-2,3-dimethylaniline (51 mg) was dissolved in N,N-dimethylformamide (2 ml) and triethylamine (1 ml) to prepare a solution. Thiophosgene (51 mg) was then added to the solution, and the mixture was stirred at room temperature for 7 hr. Next, cyclohexylhydrazine (50 mg) was added thereto, and the mixture was further stirred at room temperature for 12 hr. Ethyl acetate was added to the reaction solution, followed by washing with water and saturated brine in that order. The organic layer was then dried over anhydrous sodium sulfate. The solvent was removed by distillation under the reduced pressure, and the residue was purified by HPLC using chloroform/methanol for development to give the title compound (8 mg, yield 10%). the mixture was further stirred at room temperature for 12 hr by washing with water and saturated brine in that order The organic layer was then dried over anhydrous sodium sulfate The solvent was removed by distillation under the reduced pressure the residue was purified by HPLC

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: Prepared as described in Example 5 using cyclohexylhydrazine and 9-(4-chlorophenylsulfonyl)-2-(hydroxymethylene)-9-azabicyclo[3.3.1]nonan-3-one which was prepared as described in Example 34. Prepared was prepared