2-(2-methylpropylcarbamoylamino)acetic acid

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a round bottom flask add tert-butyl 4,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride (1.38 mmol), 2-(isobutylcarbamoylamino)acetic acid (1.15 mmol), dimethylformamide (3.8 mL), triethylamine (1.72 mmol), and HATU (1.26 mmol. Stir at room temperature for 16 hours, then dilute with water (50 mL) and ethyl acetate (50 mL). Wash the organic phase with concentrated ammonium chloride (50 mL) and brine (50 mL). Dry the organics over sodium sulfate, filter, and concentrate under reduced pressure. Purify the intermediate by flash chromatography (40 g silica gel cartridge) eluting with 0-10% methanol in ethyl acetate to yield tert-butyl 9-[2-(isobutylcarbamoylamino)acetyl]-4,9-diazaspiro[5.5]-undecane-4-carboxylate (0.38 g, 0.93 mmol): MS (m/z): 411.2 (M+H). Wash the organic phase with concentrated ammonium chloride (50 mL) and brine (50 mL) Dry the organics over sodium sulfate filter concentrate under reduced pressure Purify the intermediate by flash chromatography (40 g silica gel cartridge) eluting with 0-10% methanol in ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a round bottom flask add tert-butyl 4,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride (1.38 mmol), 2-(isobutylcarbamoylamino)acetic acid (1.15 mmol), dimethylformamide (3.8 mL), triethylamine (1.72 mmol), and HATU (1.26 mmol. Stir at room temperature for 16 hours, then dilute with water (50 mL) and ethyl acetate (50 mL). Wash the organic phase with concentrated ammonium chloride (50 mL) and brine (50 mL). Dry the organics over sodium sulfate, filter, and concentrate under reduced pressure. Purify the intermediate by flash chromatography (40 g silica gel cartridge) eluting with 0-10% methanol in ethyl acetate to yield tert-butyl 9-[2-(isobutylcarbamoylamino)acetyl]-4,9-diazaspiro[5.5]-undecane-4-carboxylate (0.38 g, 0.93 mmol): MS (m/z): 411.2 (M+H). Wash the organic phase with concentrated ammonium chloride (50 mL) and brine (50 mL) Dry the organics over sodium sulfate filter concentrate under reduced pressure Purify the intermediate by flash chromatography (40 g silica gel cartridge) eluting with 0-10% methanol in ethyl acetate

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Charge benzyl 2-(isobutylcarbamoylamino)acetate (200 g; 98.1% assay), dry Pd/C (20 g; 10% w/w), and isopropyl alcohol (2000 ml) into an autoclave. Degas under vacuum and purge with hydrogen three times. Stir at 60° C. under 50-60 psi of H2 for 4 hours. Cool the mixture to 20-30° C. and filter through diatomaceous earth and concentrate the filtrate under reduced pressure at 45-50° C. to 1-2Vol. Add acetonitrile (1000 ml) and concentrate under reduced pressure at 45-50° C. to 2-3 Vol. Cool the mixture to 5-10 C ° C. and filter. Dry the cake under reduced pressure at 45-50° C. to give of 2-(isobutylcarbamoylamino)acetic acid (112 g; 95.2% assay; 82.5% yield). Degas under vacuum purge with hydrogen three times Cool the mixture to 20-30° C. filter through diatomaceous earth concentrate the filtrate under reduced pressure at 45-50° C. to 1-2Vol Add acetonitrile (1000 ml) and concentrate under reduced pressure at 45-50° C. to 2-3 Vol. Cool the mixture to 5-10 C ° C and filter Dry the cake under reduced pressure at 45-50° C.

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a round bottom flask add tert-butyl 4,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride (1.38 mmol), 2-(isobutylcarbamoylamino)acetic acid (1.15 mmol), dimethylformamide (3.8 mL), triethylamine (1.72 mmol) and HATU (1.26 mmol. Stir at room temperature for 16 hours, then dilute with water (50 mL) and ethyl acetate (50 mL). Wash the organic phase with concentrated ammonium chloride (50 mL) and brine (50 mL). Dry the organics over sodium sulfate, filter, and concentrate under reduced pressure. Purify the intermediate by flash chromatography (40 g silica gel cartridge) eluting with 0-10% methanol in ethyl acetate to yield tert-butyl 9-[2-(isobutylcarbamoylamino)acetyl]-4,9-diazaspiro[5.5]undecane-4-carboxylate (0.38 g, 0.93 mmol): MS (m/z): 411.2 (M+H). Wash the organic phase with concentrated ammonium chloride (50 mL) and brine (50 mL) Dry the organics over sodium sulfate filter concentrate under reduced pressure Purify the intermediate by flash chromatography (40 g silica gel cartridge) eluting with 0-10% methanol in ethyl acetate

反応条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: To a round bottom flask add tert-butyl 4,9-diazaspiro[5.5]undecane-9-carboxylate hydrochloride (1.38 mmol), 2-(isobutylcarbamoylamino)acetic acid (1.15 mmol), dimethylformamide (3.8 mL), triethylamine (1.72 mmol) and HATU (1.26 mmol. Stir at room temperature for 16 hours, then dilute with water (50 mL) and ethyl acetate (50 mL). Wash the organic phase with concentrated ammonium chloride (50 mL) and brine (50 mL). Dry the organics over sodium sulfate, filter, and concentrate under reduced pressure. Purify the intermediate by flash chromatography (40 g silica gel cartridge) eluting with 0-10% methanol in ethyl acetate to yield tert-butyl 9-[2-(isobutylcarbamoylamino)acetyl]-4,9-diazaspiro[5.5]undecane-4-carboxylate (0.38 g, 0.93 mmol): MS (m/z): 411.2 (M+H). Wash the organic phase with concentrated ammonium chloride (50 mL) and brine (50 mL) Dry the organics over sodium sulfate filter concentrate under reduced pressure Purify the intermediate by flash chromatography (40 g silica gel cartridge) eluting with 0-10% methanol in ethyl acetate

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Charge benzyl 2-(isobutylcarbamoylamino)acetate (200 g; 98.1% assay), dry Pd/C (20 g; 10% w/w), and isopropyl alcohol (2000 ml) into an autoclave. Degas under vacuum and purge with hydrogen three times. Stir at 60° C. under 50-60 psi of H2 for 4 hours. Cool the mixture to 20-30° C. and filter through diatomaceous earth and concentrate the filtrate under reduced pressure at 45-50° C. to 1-2 Vol. Add acetonitrile (1000 ml) and concentrate under reduced pressure at 45-50° C. to 2-3 Vol. Cool the mixture to 5-10° C. and filter. Dry the cake under reduced pressure at 45-50° C. to give of 2-(isobutylcarbamoylamino)acetic acid (112 g; 95.2% assay; 82.5% yield). Degas under vacuum purge with hydrogen three times Cool the mixture to 20-30° C. filter through diatomaceous earth concentrate the filtrate under reduced pressure at 45-50° C. to 1-2 Vol. Add acetonitrile (1000 ml) concentrate under reduced pressure at 45-50° C. to 2-3 Vol. Cool the mixture to 5-10° C. filter Dry the cake under reduced pressure at 45-50° C.

反応条件: temp:60.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

実験手順: Charge benzyl 2-(isobutylcarbamoylamino)acetate (200 g; 98.1% assay), dry Pd/C (20 g; 10% w/w), and isopropyl alcohol (2000 ml) into an autoclave. Degas under vacuum and purge with hydrogen three times. Stir at 60° C. under 50-60 psi of H2 for 4 hours. Cool the mixture to 20-30° C. and filter through diatomaceous earth and concentrate the filtrate under reduced pressure at 45-50° C. to 1-2 Vol. Add acetonitrile (1000 ml) and concentrate under reduced pressure at 45-50° C. to 2-3 Vol. Cool the mixture to 5-10° C. and filter. Dry the cake under reduced pressure at 45-50° C. to give of 2-(isobutylcarbamoylamino)acetic acid (112 g; 95.2% assay; 82.5% yield). Degas under vacuum purge with hydrogen three times Cool the mixture to 20-30° C. filter through diatomaceous earth concentrate the filtrate under reduced pressure at 45-50° C. to 1-2 Vol. Add acetonitrile (1000 ml) concentrate under reduced pressure at 45-50° C. to 2-3 Vol. Cool the mixture to 5-10° C. filter Dry the cake under reduced pressure at 45-50° C.