2-methylcyclopropane-1-carbonyl chloride

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

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Methylcyclopropanecarboxylic acid (0.86 g, 8.6 mmol) was dissolved in DCM (10 mL) and cooled to 0° C. The solution was treated with oxalyl chloride (1.2 mL, 13.8 mmol) and DMF (0.07 mL, 0.87 mmol), allowed to warm to RT, and stirred for 2 h for complete conversion to 2-methylcyclopropanecarboxylic acid chloride. The solution was cooled to 0° C. and added via syringe to a stirred solution of semicarbazide hydrochloride (1.4 g, 12.9 mmol) and NaOH (1.4 g, 34.4 mmol) in a mixture of dioxane (10 mL) and water (2.0 mL) at 0° C. The reaction mixture was allowed to warm to RT and stirred for 12 h. The organic solvent was evaporated in vacuo, and the resultant slurry was diluted with 2 M NaOH (aq) (50 mL, 100 mmol). The suspension was stirred at 100° C. for 24 h. The aqueous solution was saturated with solid NH4Cl and extracted with EtOAc (5×50 mL). The combined organics were dried (Na2SO4) and concentrated in vacuo to afford 3-(1-methylcyclopropyl)-1H-1,2,4-triazol-5(4H)-one (0.65 g, 54.3%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.02 (m, 2H), 1.26 (s, 3H), 0.90-0.89 (m, 2H), 0.66-0.65 (m, 2H); MS (ESI) m/z: 140.1 (M+H+). to warm to RT The solution was cooled to 0° C. to warm to RT The organic solvent was evaporated in vacuo The suspension was stirred at 100° C. for 24 h extracted with EtOAc (5×50 mL) The combined organics were dried (Na2SO4) concentrated in vacuo

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Methylcyclopropanecarboxylic acid (0.86 g, 8.6 mmol) was dissolved in DCM (10 mL) and cooled to 0° C. The solution was treated with oxalyl chloride (1.2 mL, 13.8 mmol) and DMF (0.07 mL, 0.87 mmol), allowed to warm to RT, and stirred for 2 h for complete conversion to 2-methylcyclopropanecarboxylic acid chloride. The solution was cooled to 0° C. and added via syringe to a stirred solution of semicarbazide hydrochloride (1.4 g, 12.9 mmol) and NaOH (1.4 g, 34.4 mmol) in a mixture of dioxane (10 mL) and water (2.0 mL) at 0° C. The reaction mixture was allowed to warm to RT and stirred for 12 h. The organic solvent was evaporated in vacuo, and the resultant slurry was diluted with 2 M NaOH (aq) (50 mL, 100 mmol). The suspension was stirred at 100° C. for 24 h. The aqueous solution was saturated with solid NH4Cl and extracted with EtOAc (5×50 mL). The combined organics were dried (Na2SO4) and concentrated in vacuo to afford 3-(1-methylcyclopropyl)-1H-1,2,4-triazol-5(4H)-one (0.65 g, 54.3%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.02 (m, 2H), 1.26 (s, 3H), 0.90-0.89 (m, 2H), 0.66-0.65 (m, 2H); MS (ESI) m/z: 140.1 (M+H+). to warm to RT The solution was cooled to 0° C. to warm to RT The organic solvent was evaporated in vacuo The suspension was stirred at 100° C. for 24 h extracted with EtOAc (5×50 mL) The combined organics were dried (Na2SO4) concentrated in vacuo

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

Procedure: In analogy to the procedure for Example 36A, 150 mg (0.67 mmol) 6-(1-aminopropyl)-3-cyclopentyl-1,2,4-triazin-5(4H)-one, 90 mg (0.74 mmol) 2-methyl-cyclopropylcarbonyl chloride and proportionate amounts of the other reagents are used. The crude product is used in the next step without further purification. The crude product is used in the next step without further purification

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

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

Procedure: In analogy to the procedure for Example 36A, 150 mg (0.67 mmol) 6-(1-aminopropyl)-3-cyclopentyl-1,2,4-triazin-5(4H)-one, 90 mg (0.74 mmol) 2-methyl-cyclopropylcarbonyl chloride and proportionate amounts of the other reagents are used. The crude product is used in the next step without further purification. The crude product is used in the next step without further purification

Conditions: temp:0.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 2-Methylcyclopropanecarboxylic acid (0.86 g, 8.6 mmol) was dissolved in DCM (10 mL) and cooled to 0° C. The solution was treated with oxalyl chloride (1.2 mL, 13.8 mmol) and DMF (0.07 mL, 0.87 mmol), allowed to warm to RT, and stirred for 2 h for complete conversion to 2-methylcyclopropanecarboxylic acid chloride. The solution was cooled to 0° C. and added via syringe to a stirred solution of semicarbazide hydrochloride (1.4 g, 12.9 mmol) and NaOH (1.4 g, 34.4 mmol) in a mixture of dioxane (10 mL) and water (2.0 mL) at 0° C. The reaction mixture was allowed to warm to RT and stirred for 12 h. The organic solvent was evaporated in vacuo, and the resultant slurry was diluted with 2 M NaOH (aq) (50 mL, 100 mmol). The suspension was stirred at 100° C. for 24 h. The aqueous solution was saturated with solid NH4Cl and extracted with EtOAc (5×50 mL). The combined organics were dried (Na2SO4) and concentrated in vacuo to afford 3-(1-methylcyclopropyl)-1H-1,2,4-triazol-5(4H)-one (0.65 g, 54.3%) as a white solid. 1H NMR (400 MHz, DMSO-d6): δ 11.02 (m, 2H), 1.26 (s, 3H), 0.90-0.89 (m, 2H), 0.66-0.65 (m, 2H); MS (ESI) m/z: 140.1 (M+H+). to warm to RT The solution was cooled to 0° C. to warm to RT The organic solvent was evaporated in vacuo The suspension was stirred at 100° C. for 24 h extracted with EtOAc (5×50 mL) The combined organics were dried (Na2SO4) concentrated in vacuo

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

Procedure: In analogy to the procedure for Example 36A, 150 mg (0.67 mmol) 6-(1-aminopropyl)-3-cyclopentyl-1,2,4-triazin-5(4H)-one, 90 mg (0.74 mmol) 2-methyl-cyclopropylcarbonyl chloride and proportionate amounts of the other reagents are used. The crude product is used in the next step without further purification. The crude product is used in the next step without further purification