Water → HCID 24995588, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 5-[4-(methylsulfonyl)phenyl]-2-pyrazinol (and tautomers thereof) (prepared as in Example 145, Step 2, 1.3 g, 5.19 mmol), (1R)-1-{1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}ethyl methanesulfonate (2.23 g, 7.0 mmol, 70% ee) and K2CO3 (1.45 g, 10.4 mmol) in DMF (35 mL) was stirred at 100° C. in a preheated oil bath overnight. The mixture was cooled to ambient temperature, treated with water, and the mixture was extracted with EtOAc (75 mL×2). The combined organic extracts were washed with water, brine and dried over Na2SO4, filtered, and the filtrate was concentrated to a brown oil, which was by chromatography on a silica gel column eluted with 50% EtOAc/hexanes followed by chromatography on an ISCO silica gel column using 0 to 60% EtOAc/hexanes to give 2-[((1S)-1-{1-[3-(1-methylethyl)-1,2,4-oxadiazol-5-yl]-4-piperidinyl}ethyl)oxy]-5-[4-(methylsulfonyl)phenyl]pyrazine (0.73 g, 70% ee, 30%) as a white solid. The solid was subjected to chiral separation (similar to conditions used above for Example 158) to yield 0.30 g of the title compound as a white solid. 1H NMR (400 MHz, CDCl3): δ 8.53 (d, 1H, J=1.3 Hz), 8.25 (d, 1H, J=1.3 Hz), 8.10 (d, 2H, J=8.3 Hz), 8.02 (d, 2H, J=8.5 Hz), 5.20-5.10 (m, 1H), 4.35-4.20 (m, 2H), 3.15-3.00 (m, 5H), 2.90 (septet, 1H, J=7.0 Hz), 2.00-1.80 (m, 3H), 1.60-1.40 (m, 2H), 1.34 (d, 3H, J=6.3 Hz), 1.28 (d, 6H, J=6.9 Hz); LRMS (ESI), m/z 472 (M+H).

Provenance & Evidence