Hydrochloric Acid → HCID 58169872, compound

Participants

Reaction Conditions

Reaction Steps

A solution of trimethyloxonium tetrafluoroborate (5.39 mg, 0.036 mmol) and (5S,7R)—N-{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}-7-(4-fluoro-2-methylphenyl)-N-methyl-2-oxo-1,8-diazaspiro[4.5]decane-8-carboxamide (Intermediate 42, 17 mg, 0.030 mmol) in Dichloromethane (DCM) (2 ml) was stirred at rt for 3 hrs. The mixture was washed with NaHCO3 saturated solution and the aqueous layer was extracted with DCM. The organic layers were combined, filtered through a phase separator tube and concentrated. The residue was dissolved in Methanol (2 ml) and to this solution, cooled to 0° C., was added Sodium cyanoborohydride (5.73 mg, 0.091 mmol). A solution of 1.25M HCl in MeOH was added maintaining the pH around 3-4 and the reaction was left stirring at rt overnight. To the solution NaHCO3 saturated solution and DCM were added and the aqueous layer was extracted with DCM. Organic layers were combined, filtered through a phase separator tube and concentrated. The crude was purified by SP4 (12M cartridge; eluting from 90%:10% to 50%:50% Cy:EtOAc). Relevant fractions were collected obtaining the title compound (13 mg, 0.024 mmol, 78% yield); 1H NMR (500 MHz, DMSO-d6) δ ppm 8.01 (s, 1H) 7.69 (s, 2H) 7.15-7.21 (m, 1H) 6.94 (dd, 1H) 6.83 (t, 1H) 5.20-5.41 (m, 1H) 4.02-4.27 (m, 1H) 3.35-3.44 (m, 1H) 3.02-3.20 (m, 2H) 2.86 (t, 1H) 2.76 (s, 3H) 2.34 (s, 3 H) 1.59-2.19 (m, 8H) 1.47 (d, 3H); UPLC: Rt=0.68 mins, m/z=546 [M+H]+; HPLC: Rt=5.67 mins.

Provenance & Evidence