Hexylamine → methyl 3-(5-(2-ethyl-4-(hexylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyridin-2-yloxy)-2,2-dimethylpropanoate

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Reaction Steps

n-Hexylamine (23.0 μL, 0.173 mmol) was added dropwise to a solution of methyl 3-(5-(4-(chlorocarbonyl)-2-ethyl-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyridin-2-yloxy)-2,2-dimethylpropanoate B-11 (50.0 mg, 0.115 mmol) and N-ethyl-N,N-diisopropylamine (40.2 μL, 0.231 mmol) in anhydrous methylene chloride (1.10 mL) at 0° C. under an atmosphere of argon. The reaction mixture was slowly warmed to room temperature and stirred for 8 h, then sequentially diluted with methylene chloride (30 mL), quenched with an aqueous pH 7 phosphate buffer solution (15 mL) and decanted. The aqueous layer was extracted with methylene chloride (3×30 mL); the combined extracts were successively washed with an aqueous pH 7 phosphate buffer solution (20 mL), brine (20 mL), dried over anhydrous magnesium sulfate, filtered and concentrated to dryness under reduced pressure. Crude methyl 3-(5-(2-ethyl-4-(hexylcarbamoyl)-3,4-dihydro-2H-benzo[b][1,4]oxazin-7-yl)pyridin-2-yloxy)-2,2-dimethylpropanoate B-12 (55.2 mg, Yield=96%) was obtained as a light tan solid and was used for the next step without further purification. MS (ESI) [M+1]+ 498.

Provenance & Evidence