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

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Reaction Steps

Experimental conditions analogous to Example 15, from 0.27 g (0.62 mmol) of (S)-2-{[(benzofuran-2-ylmethyl)-amino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester trifluoroacetic acid salt, was dissolved 1 mL dichloromethane, 216 μL (1.55 mmol) of triethylamine, and 0.16 g (0.68 mmol) of 7-methoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carbonyl chloride were added to this mixture. The crude mixture was filtered through silica and the Boc-deprotection was conducted in 4 mL 10% trifluoroacetic acid/dichloromethane in 2 hours, followed by aqueous sodium bicarbonate quench and submitting the crude material to reductive amination reaction in dichloromethane using 0.24 g (3.1 mmol) of cyclobutanone and 0.657 g (3.1 mmol) of sodium triacetoxyborohydride. After 5 hours the reaction was quenched with aqueous sodium bicarbonate and di-tert-butyl dicarbonate. The residue from the organic layer was purified using flash chromatography (7N ammonia in methanol, 0-3% in dichloromethane), gave 49 mg off-white solid as a free base solid. LC-MSD, m/z for C29H34N2O5 [M+H]+: 491.2. 1H NMR (400 MHz, CDCl3/HCl): δ 1.7 (s, 6 H), 1.8-2.1 (m, 6 H), 2.1-2.2 (m, 1 H), 2.3-2.4 (m, 1 H), 2.5-2.7 (m, 2 H), 2.8-2.9 (m, 1 H), 3.5-3.7 (m, 1 H), 3.7-3.9 (m, 3 H), 3.9 (s, 3 H), 4.0-4.1 (m, 1 H), 4.8-5.0 (m, 2 H), 6.8 (s, 1H), 6.9 (s, 1 H), 7.0 (s, 1 H), 7.2-7.3 (m, 2H), 7.4-7.5 (m, 1 H), 7.5-7.6 (m, 1 H), 12.0-12.1 (bs, 1 H).

Provenance & Evidence