Diethyl Ether → HCID 59632037, compound

Participants

Reaction Steps

To a cooled (−78° C.) solution of methyl 5-(4-(azetidine-1-carbonyl)phenyl)-1-(2-chlorophenyl)-1H-pyrazole-3-carboxylate (138 mg, 0.35 mmol) in THF (5 mL) was added methylmagnesium bromide (0.3 mL of a 3.0M solution in ether, 0.9 mmol). The resulting brown solution was allowed to slowly warm to ambient temperature overnight. The reaction was then quenched by the addition of saturated aqueous ammonium chloride solution and EtOAc. The aqueous was extracted with EtOAc (3×) and the combined organic extracts were washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure to afford a yellow film. This crude product was purified by flash column chromatography eluting with a gradient of 0% to 10% MeOH in CH2Cl2. The main peak was collected and was ˜85% pure by HPLC. This material was further purified by reverse phase preparative HPLC eluting with MeCN/H2O with 0.1% TFA. The product fractions from the HPLC were made basic by the careful addition of solid Na2CO3. The resulting mixture was concentrated to remove most of the MeCN. The resulting aqueous suspension was extracted with CH2Cl2 (3×), and the combined extracts were dried over Na2SO4 overnight, filtered and concentrated under reduced pressure to afford azetidin-1-yl(4-(1-(2-chlorophenyl)-3-(2-hydroxypropan-2-yl)-1H-pyrazol-5-yl)phenyl)methanone (43 mg, 31% yield) as a pale brown powder. 1H NMR (400 MHz CDCl3): δ 7.54-7.48 (2H, m), 7.46-7.40 (2H, m), 7.39-731 (2H, m), 7.24-7.19 (2H, m), 6.54 (1H, s), 4.32-4.16 (4H, m), 2.63 (1H, s), 2.38-2.28 (2H, m), 1.68 (6H, s). MS(ES): 396 [M+H]+.

Provenance & Evidence