propan-2-ylhydrazine

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: 4-(1-Benzyl-1H-imidazol-2-ylmethyl)-3,5-diethyl-1-isopropyl-1H-pyrazole was prepared from 4-(1-benzyl-1H-imidazol-2-ylmethyl)-heptane-3,5-dione and isopropylhydrazine in analogy to Example 190 b): light yellow viscous oil; MS (ISP): 337.3 ((M+H)+.).

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

Procedure: 4-(1-Benzyl-1H-imidazol-2-ylmethyl)-3,5-diethyl-1-isopropyl-1H-pyrazole was prepared from 4-(1-benzyl-1H-imidazol-2-ylmethyl)-heptane-3,5-dione and isopropylhydrazine in analogy to Example 190 b): light yellow viscous oil; MS (ISP): 337.3 ((M+H)+.).

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of ethoxymethylenemalonitrile (0.55 g, 4.5 mmol) and iso-propylhydrazine (0.50 g, 4.5 mmol) in ethanol (10 mL) in a 10-20 mL Smith process vial was treated with triethylamine (0.88 mL). The vial was capped and heated in the microwave reactor for one hour at 150° C. Following cooling of the vial, the mixture was concentrated to dryness under reduced pressure. The residue was partitioned between ethyl acetate and water. The aqueous phase was extracted with ethyl acetate. The combined organic extracts were washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and concentrated to dryness under reduced pressure to provide 5-amino-1-isopropyl-1H-pyrazole-4-carbonitrile as a slowly solidifying syrup (0.72 g, >100%). MS (ES+): 151.2 (M+H)+ The vial was capped Following cooling of the vial, the mixture was concentrated to dryness under reduced pressure The residue was partitioned between ethyl acetate and water The aqueous phase was extracted with ethyl acetate The combined organic extracts were washed with saturated aqueous sodium chloride solution dried over anhydrous magnesium sulfate filtered concentrated to dryness under reduced pressure

Conditions: temp:150.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of ethoxymethylenemalonitrile (0.55 g, 4.5 mmol) and iso-propylhydrazine (0.50 g, 4.5 mmol) in ethanol (10 mL) in a 10-20 mL Smith process vial was treated with triethylamine (0.88 mL). The vial was capped and heated in the microwave reactor for one hour at 150° C. Following cooling of the vial, the mixture was concentrated to dryness under reduced pressure. The residue was partitioned between ethyl acetate and water. The aqueous phase was extracted with ethyl acetate. The combined organic extracts were washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and concentrated to dryness under reduced pressure to provide 5-amino-1-isopropyl-1H-pyrazole-4-carbonitrile as a slowly solidifying syrup (0.72 g, >100%). MS (ES+): 151.2 (M+H)+ The vial was capped Following cooling of the vial, the mixture was concentrated to dryness under reduced pressure The residue was partitioned between ethyl acetate and water The aqueous phase was extracted with ethyl acetate The combined organic extracts were washed with saturated aqueous sodium chloride solution dried over anhydrous magnesium sulfate filtered concentrated to dryness under reduced pressure

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

Procedure: The title compound was prepared as TFA salt according to procedure for Example 69A-69F, substituting (±)-1-benzyl 2-methyl pyrrolidine-1,2-dicarboxylate for (R)-1-benzyl 2-methyl pyrrolidine-1,2-dicarboxylate and isopropylhydrazine for (2,2,2-Trifluoro-ethyl)-hydrazine HCl salt. MS (DCI): m/z 315 (M+H)+; 1H NMR (500 MHz, CD3OD): δ 1.51 (dd, J=6.71, 3.66 Hz, 6H), 1.71-1.95 (m, 3H), 2.05-2.25 (m, 2H), 2.24-2.37 (m, 1H), 2.41-2.56 (m, 2H), 2.69-2.78 (m, 1H), 2.77-2.89 (m, 1H), 2.90-3.03 (m, 1H), 2.96 (s, 3H), 3.29-3.44 (m, 2H), 3.77-3.96 (m, 1H), 4.73-4.91 (m, 2H).

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

Procedure: tert-Butyl (3E)-3-[(dimethylamino)methylidene]-4-oxopiperidine-1-carboxylate was condensed with propan-2-ylhydrazine; removal of the protecting group provided 2-(propan-2-yl)-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine. removal of the protecting group

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

Procedure: tert-Butyl (3E)-3-[(dimethylamino)methylidene]-4-oxopiperidine-1-carboxylate was condensed with propan-2-ylhydrazine; removal of the protecting group provided 2-(propan-2-yl)-4,5,6,7-tetrahydro-2H-pyrazolo[4,3-c]pyridine. removal of the protecting group

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

Procedure: To a solution of 7.4 g (100.0 mmol) of isopropylhydrazine in 100 ml of ethanol was added dropwise under stirring 23.3 g (purity: 85.0%, 100.0 mmol) of ethyl 4,4,4-trifluoro-2-methyl-3-oxobutanoate under ice-cooling so that the temperature in the reaction system did not exceed 10° C. After the dropwise addition, the whole was stirred at room temperature for 30 minutes. Then, 1 ml of concentrated hydrochloric acid was added into the reaction solution, followed by 2 days of stirring under refluxing. After the completion of the reaction was confirmed, the solvent was removed by evaporation under reduced pressure. Water was added to the residue, followed by extraction with ethyl acetate. The resulting organic layer was washed with water and saline, successively, and then dried over anhydrous magnesium sulfate. The solvent was removed by evaporation under reduced pressure and the residue was washed with n-hexane to obtain 18.1 g (yield: 87.0%) of 5-hydroxy-4-methyl-1-iso-propyl-3-trifluoromethyl-1H-pyrazole as white crystals (melting point: 150 to 153° C.). cooling so that the temperature in the reaction system did not exceed 10° C After the dropwise addition followed by 2 days of stirring under refluxing the solvent was removed by evaporation under reduced pressure Water was added to the residue followed by extraction with ethyl acetate The resulting organic layer was washed with water and saline successively, and then dried over anhydrous magnesium sulfate The solvent was removed by evaporation under reduced pressure the residue was washed with n-hexane

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

Procedure: To a solution of 7.4 g (100.0 mmol) of isopropylhydrazine in 100 ml of ethanol was added dropwise under stirring 23.3 g (purity: 85.0%, 100.0 mmol) of ethyl 4,4,4-trifluoro-2-methyl-3-oxobutanoate under ice-cooling so that the temperature in the reaction system did not exceed 10° C. After the dropwise addition, the whole was stirred at room temperature for 30 minutes. Then, 1 ml of concentrated hydrochloric acid was added into the reaction solution, followed by 2 days of stirring under refluxing. After the completion of the reaction was confirmed, the solvent was removed by evaporation under reduced pressure. Water was added to the residue, followed by extraction with ethyl acetate. The resulting organic layer was washed with water and saline, successively, and then dried over anhydrous magnesium sulfate. The solvent was removed by evaporation under reduced pressure and the residue was washed with n-hexane to obtain 18.1 g (yield: 87.0%) of 5-hydroxy-4-methyl-1-iso-propyl-3-trifluoromethyl-1H-pyrazole as white crystals (melting point: 150 to 153° C.). cooling so that the temperature in the reaction system did not exceed 10° C After the dropwise addition followed by 2 days of stirring under refluxing the solvent was removed by evaporation under reduced pressure Water was added to the residue followed by extraction with ethyl acetate The resulting organic layer was washed with water and saline successively, and then dried over anhydrous magnesium sulfate The solvent was removed by evaporation under reduced pressure the residue was washed with n-hexane

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

Procedure: To ethyl 2,4-dioxopentanoate (20.1 g, 127 mmol) in acetic acid (100 mL) at 0° C. was added drop-wise isopropylhydrazine (9.42 g, 127 mmol). The cold bath was removed and the reaction mixture was stirred for 2 hours. The reaction mixture was then diluted with EtOAc/H2O (300 mL/100 mL). The organic layer was washed with saturated NaHCO3 aqueous solution (100 mL), H2O (50 mL) and brine (50 mL). The organic layer was dried (Na2SO4) and concentrated. The residue was purified by silica gel flash chromatography (1:2 EtOAc/hexane) to give the desired product (31%). The cold bath was removed The reaction mixture was then diluted with EtOAc/H2O (300 mL/100 mL) The organic layer was washed with saturated NaHCO3 aqueous solution (100 mL), H2O (50 mL) and brine (50 mL) The organic layer was dried (Na2SO4) concentrated The residue was purified by silica gel flash chromatography (1:2 EtOAc/hexane)