Diisopropylethylamine → (3R*,4S*)-4-carbomethoxymethyl-3-(5-chloroindole-2-carbonylamino)-3,4-dihydrocarbostyril

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A 1 mL reaction vessel was charged with trans 3-amino-4-carbomethoxymethyl-3,4-dihydrocarbostyril trifluoroacetic acid salt (13 mg, 0.04 mmol), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (9 mg, 0.05 mmol), 1-hydroxy-7-azabenzotriazole (7 mg, 0.05 mmol), 5-chloroindole-2-carboxylic acid (8 mg, 0.04 mmol) and N,N-dimethylformamide (0.3 mL). After the solids dissolved during stirring at room temperature under argon, diisopropylethylamine (14 mg, 0.11 mmol) was added, and the solution was stirred for 1 h before it was diluted with water (0.2 mL) and methanol (0.8 mL). Purification by reverse phase preparative HPLC using trifluoroacetic acid containing solvents gave the title compound (8.5 mg, 56% yield) as a white solid. 1H NMR (d8-THF, 400 MHz) δ 11.2 (s, 1H), 9.6 (s, 1H), 8.06 (d, 1H, J=8.9 Hz), 7.64 (d, 1H, J=1.9 Hz), 7.43 (d, 1H, J=8.7 Hz), 7.24–6.87 (m, 6H), 4.84 (dd, 1H, J=8.8, 13.0 Hz), 3.67 (m, 1H), 3.59 (s, 3H), 2.89 (d, 2H, J=6.2 Hz). HPLC/MS [M+H]+, 412.

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