Hydrochloric Acid → HCID 86651623, compound

Participants

Reaction Conditions

Reaction Steps

A solution of trimethyloxonium tetrafluoroborate (33.5 mg, 0.226 mmol) and methyl (5R,7R)-8-{[{(1R)-1-[3,5-bis(trifluoromethyl)phenyl]ethyl}(methyl)amino]carbonyl}-7-(4-fluoro-2-methylphenyl)-2-oxo-1,8-diazaspiro[4.5]decane-4-carboxylate (Intermediate 40, 70 mg, 0.113 mmol) in Dichloromethane (DCM) (3 ml) was stirred at rt overnight. 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 obtained was dissolved in Methanol (3 ml) and to the solution, cooled to 0° C., was added sodium cyanoborohydride (28.5 mg, 0.454 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 for 2 hrs. To the solution NaHCO3 saturated solution and DCM were added and the aqueous layer was extracted with DCM. Organic layers were combined and 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 (12 mg, 0.020 mmol, 17.54% yield) as a single diasteroisomer. 1H NMR (500 MHz, DMSO-d6) δ ppm 7.99 (s, 1H) 7.68 (s, 2H) 7.13 (dd, 1H) 6.89 (dd, 1H) 6.76 (t, 1H) 5.20-5.40 (m, 1H) 4.43 (dd, 1H) 3.61 (s, 3H) 3.11-3.19 (m, 1H) 3.01-3.10 (m, 1H) 2.89-2.97 (m, 1H) 2.80-2.88 (m, 1H) 2.71 (s, 3H) 2.45-2.55 (m, 1H) 2.32 (s, 3H) 1.85-2.05 (m, 2H) 1.61-1.71 (m, 1H) 1.53-1.60 (m, 2H) 1.46 (d, 3H) 1.38-1.50 (m, 1H); Despite some signals' overlapping (H10 eq and H6 eq), causing missing information, stereochemistry could be assigned on the basis of the following noe data:

Provenance & Evidence