1,2-Dichloroethane → [(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-6-[(9aS)-hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-2-methyl-4-pyrimidinyl}hydrazino)-3-oxopropyl][(phenylmethyl)oxy]formamide

Participants

Reaction Steps

To a solution of (2R)-3-cyclopentyl-2-({formyl[(phenylmethyl)oxy]amino}methyl)propanoic acid, N,N-diisopropylethylamine salt, isopropanol solvate (33.64 g, 68.0 mmol) in DMF (230 mL) was added (9aS)-8-(5-fluoro-6-hydrazino-2-methyl-4-pyrimidinyl)octahydropyrazino[2,1-c][1,4]oxazine (20.16 g, 71.4 mmol), N-methylmorpholine (30 mL, 273 mmol), 1-hydroxy-7-azabenzotriazole (11.10 g, 81.6 mmol), and EDC (15.64 g, 81.6 mmol). The solution was stirred overnight and then diluted with Et2O (500 mL). The mixture was washed with water (2×200 mL), and the combined aqueous phase was extracted with a fresh portion of Et2O (100 mL). This Et2O phase was then washed with water (50 mL). This extraction-wash procedure was repeated 6 times, and the total combined organic phase was then diluted with DCM (250 mL). The organic phase was then dried over anhydrous Na2SO4, filtered, and concentrated in vacuo to give crude [(2R)-2-(cyclopentylmethyl)-3-(2-{5-fluoro-6-[(9aS)-hexahydropyrazino[2,1-c][1,4]oxazin-8(1H)-yl]-2-methyl-4-pyrimidinyl}hydrazino)-3-oxopropyl][(phenylmethyl)oxy]formamide (42.32 g, >100% crude yield) as a light yellow foam. LCMS: (M+H)+: 570.3.

Provenance & Evidence