Dimethylamine → 3-(3-Chloro-4-pyrrolidin-1-ylmethyl-phenyl)-3-hydroxy-cyclobutanecarboxylic acid dimethylamide

Participants

Reaction Steps

To a solution of crude intermediate 17, 3-(3-chloro-4-((pyrrolidin-1-yl)methyl)phenyl)-3-hydroxycyclobutanecarboxylic acid (˜4.3 mL ˜0.65 mmol) was added dimethylamine in THF (0.65 ml, 1.29 mmol, 2.0M THF) and T3P (50 wt % solution in EtOAc, 0.62 m, 0.97 mmol). The resulting reaction mixture was stirred at RT for 1 hr and then 25 ml of 1N NaOH and 100 ml of EtOAc were added and the layers were separated. The aqueous layer was subjected to EtOAc extraction (2×60 ml) again and the combined organic layers were dried over MgSO4 and evaporated. The residue was purified by flash column chromatography using a 40 g ISCO™ column, eluting with 5% MeOH/CH2Cl2 containing 0.25% NH4OH. The product containing fractions were collected and concentrated under reduced pressure to give the title compound (112 mg, 52% yield). Rf=0.65 (20% MeOH/CH2CH2+0.2% NH4OH); LRMS m/z Calcd for C18H25ClN2O2, 336.8, found, 337.1 (M+1) APCI; 400 MHz 1H NMR (CDCl3) δ (d, J=1.7 Hz, 1H), 7.46, 7.40 (d, J=7.9 Hz, 1H), 7.33 (dd, J=7.9, 1.7 Hz, 1H), 3.68 (s, 2H), 3.06-2.96 (m, 1H); 2.92 (s, 6H), 2.78-2.68 (m, 2H), 2.62-2.46 (m, 6H): 1.76-1.68 (m, 4H); 100 MHz 13C NMR (CDCl3) δ 175.5, 146.2, 135.5, 133.9, 130.7, 126.5, 123.7, 72.9, 56.8, 54.3, 40.9, 37.4, 36.1, 28.5, 23.7.

Provenance & Evidence