Formic Acid → HCID 78080314, compound

Participants

Reaction Conditions

Reaction Steps

To an orange suspension containing 3-chloro-5-(((7-methyl-3-neopentyl-2-oxo-1-oxa-3-azaspiro[4.5]decan-7-yl)methyl)amino)-4-nitrobenzonitrile (0.132 g, 0.294 mmol) in MeOH (5.44 mL) was added iron (325 mesh) (0.164 g, 2.94 mmol), trimethyl orthoformate (0.325 mL, 2.94 mmol), and formic acid (0.113 mL, 2.94 mmol). The resulting solution was stirred at 65° C. for 26 h. Additional trimethyl orthoformate (0.325 mL, 2.94 mmol) and formic acid (0.113 mL, 2.94 mmol) was added, and stirring was continued at 65° C. for 24 h. The reaction was cooled to rt and concentrated. The resulting residue was suspended in MeCN (2 mL) and DMSO (4 mL) and filtered through a Hirsch funnel to remove any remaining solids. The filtrate was purified using reverse-phase HPLC (Sunfire Prep C18 column (30×150 mm); 14 minute run; 25 mL/min flow rate with at-column dilution; Solvent A: MeCN/0.1% TFA, Solvent B: water/0.1% TFA, gradient: 40-90% solvent A) to provide the title compound (0.101 g, 62% yield) as a TFA salt. 1H NMR (400 MHz, DMSO-d6) δ 8.55 (s, 1H), 8.41 (d, J=1.25 Hz, 1H), 7.81 (d, J=1.25 Hz, 1H), 4.15 (s, 2H), 3.29 (dd, J=9.03, 20.33 Hz, 2H), 2.87 (s, 2H), 1.80 (d, J=13.55 Hz, 1H), 1.49-1.74 (m, 4H), 1.22-1.48 (m, 3H), 1.02 (s, 3H), 0.85 (s, 9H). MS (m/z) 429.2 (M+H+).

Provenance & Evidence