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

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Reaction Steps

73 mg of (S)-2-{[(7-methoxy-2,2-dimethyl-benzo[1,3]dioxole-5-carbonyl)-quinoxalin-2-ylmethyl-amino]-methyl}-pyrrolidine-1-carboxylic acid tert-butyl ester were dissolved in 3 mL 10% trifluoroacetic acid/dichloromethane and neutralized with aqueous sodium bicarbonate after 2 hours. The crude material was submitted to reductive amination reaction in dichloromethane using 53 mg (0.67 mmol) of cyclobutanone and 0.14 g (0.67 mmol) sodium triacetoxyborohydride. After overnight the reaction was quenched with aqueous sodium bicarbonate and purified using reverse phase HPLC, mobile phase with a gradient 10-70% acetonitrile in 40 min. The residue was dissolved in dichloromethane, washed with aqueous sodium bicarbonate, dried with anhydrous magnesium sulfate and evaporated in vacuum to yield 42 mg pale yellow solid as the free base. LC-MSD, m/z for C29H34N4O4 [M+H]+: 503.6. 1H NMR (400 MHz, CDCl31HCl): δ 1.7 (s, 6 H), 1.7-3.0 (m, 11 H), 3.6-4.2 (m, 8 H), 5.3-5.4 (m, 1 H), 5.8-5.9 (m, 1 H), 6.6 (s, 1 H), 6.8 (s, 1 H), 8.0 (bs, 2 H), 8.3 (bs, 1 H), 8.5-8.6 (m, 1 H), 9.1 (bs, 1 H), 12.0 (bs, 1 H).

Provenance & Evidence