Triethylamine → 7-Methoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carboxylic acid benzo[b]thiophen-2-ylmethyl-((S)-1-cyclobutyl-pyrrolidin-2-ylmethyl)-amide

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Reaction Steps

Experimental conditions were analogous to Example 58, from 0.29 g (0.84 mmol) of (S)-2-{[(benzo[b]thiophen-2-ylmethyl)-amino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester, 10 mL dichloromethane, 141 μL (1.01 mmol) of triethylamine, and 0.22 mg (0.92 mmol) of 7-methoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carbonyl chloride. The crude mixture was filtered through silica and the Boc-deprotection was conducted in 10 mL 10% trifluoroacetic acid/dichloromethane in 2 hours, followed by aqueous sodium bicarbonate quench. The crude material from organic layer was alkylated in 5 mL dichloromethane, with 0.2 g (2.5 mmol) of cyclobutanone and 0.53 mg (2.5 mmol) of sodium triacetoxyborohydride. After 2 days the reaction was quenched with aqueous sodium bicarbonate and di-tert-butyl dicarbonate. The residue from the organic layer was purified using reverse phase HPLC, mobile phase with a gradient 15-80% acetonitrile in 50 min., gave 92 mg of off-white solid as the free base. LC-MSD, m/z for C29H34N2O4S [M+H]+: 507.6. 1H NMR (400 MHz, CDCl3): δ 1.5-3.5 (m, 16 H), 1.7 (s, 6 H), 3.8 (bs, 3 H), 5.0 (bs, 2 H), 6.6 (s, 1 H), 6.7 (s, 1 H), 7.2 (bs, 1 H), 7.3-7.4 (m, 2 H), 7.7-7.8 (m, 1 H), 7.8-7.9 (m, 1 H).

Provenance & Evidence