Guanidine Hydrochloride → Benzyl 4-[3-(2-aminopyrimidin-4-yl)-2-(4-fluorophenyl)imidazo[1,2-a]pyridin-7-yl]piperidine-1-carboxylate

Participants

Reaction Conditions

Reaction Steps

A 28 mL Pyrex Plus tube was charged with ketone 35 (420 mg, 0.89 mmol), DMFDMA (530 mg, 4.45 mmol) and toluene (10 mL). The reaction was heated to 100° C. for 7 hours, after which more DMFDMA (530 mg, 4.45 mmol) was added, and the reaction was allowed to heat at 100° C. for 12 more hours. The reaction was then concentrated under reduced pressure, and then dissolved in 1-propanol (20 mL). The reaction was then charged with guanidine-HCl (128 mg, 1.34 mmol) and sodium methoxide (305 □L of a 25% (w/w) solution in methanol, 1.34 mmol), and the reaction was heated to 80° C. for 18 hours. The reaction was then concentrated under reduced pressure, then dissolved in 10 mL CH2Cl2, then loaded onto a 40 g Isco RediSep normal phase silica cartridge, and purified on an Isco OptiX10 CombiFlash instrument using a gradient that started at 100% heptane and ended at 100% ethyl acetate. Fractions containing desired product were pooled and concentrated under reduced pressure. Yield of 37: 190 mg (41% over both steps). 1H NMR (400 MHz, CDCl3) δ 1.62 (m, 2H), 1.88 (m, 2H), 2.74 (m, 1H), 2.91 (m, 2H), 4.34 (bs, 2H), 5.14 (s, 2H), 5.21 (s, 2H), 6.48 (d, J=5.2 Hz, 1H), 6.74 (d, J=7.2 Hz, 1H), 7.09 (t, J=8.8 Hz, 2H), 7.34 (m, 5H), 7.44 (bs, 1H), 7.60 (m, 2H), 8.08 (d, J=5.2 Hz, 1H), 9.40 (d, J=7.2 Hz, 1H). MS (ESI+) 523.7.

Provenance & Evidence