Ammonium Chloride → 8-Carbamoyl-7-cyano-6-phenyl-3,4-dihydro-1H-pyrrolo[1,2-a]pyrazine-2-carboxylic acid tert-butyl ester

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Reaction Steps

A stirred solution of triethylamine (3.34 mL), 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (2.30 g) and 1-hydroxybenzotriazole hydrate (1.62 g) in dry dimethylformamide (120 mL) was treated with 7-cyano-6-phenyl-3,4-dihydro-1H-pyrrolo[1,2-a]pyrazine-2,8-dicarboxylic acid 2-tert-butyl ester (4.40 g, Reference Example 19). After stirring at room temperature for a further 15 minutes the reaction mixture was treated with ammonium chloride (1.28 g) and then heated at 80° C. for 5 hours. The reaction mixture was allowed to cool to room temperature and then evaporated. The residue was treated with water and ethyl acetate. The organic phase was separated, washed with a 1M aqueous solution of sodium hydroxide (20 mL) and then water (20 mL). The organic phase was then dried over magnesium sulfate and evaporated to give a brown gum. The gum was triturated with diethyl ether to give the title compound (3.80 g) as a white solid, m.p. 214–215° C. 1H NMR [(CD3)2SO]: δ 7.59–7.50 (m, 5H), 7.41–7.27 (bs, 1H), 7.08–6.93 (bs, 1H), 4.75 (s, 2H), 3.92 (t, 2H), 3.62 (t, 2H) and 1.40 (s, 9H).

Provenance & Evidence