Sodium ethoxide → Tert-butyl 4-({4-[6-(4-fluorophenyl)imidazo[2,1-b][1,3]oxazol-5-yl]pyrimidin-2-yl}amino)piperidine-1-carboxylate

Participants

Reaction Steps

A mixture of 3-(dimethylamino)-1-[6-(4-fluorophenyl)imidazo[2,1-b][1,3]oxazol-5-yl]prop-2-en-1-one (4.24 g, 14.2 mmol) and tert-butyl 4-{[amino(imino)methyl]amino}-piperidine-1-carboxylate hydrochloride (5.92 g, 21.2 mmol) was diluted with 40 ml of absolute ethanol and treated with 1.35 eq. of a 21% w/w solution of sodium ethoxide in ethanol (7.2 ml) to form a reaction mixture. The reaction mixture was heated to reflux for 15 hours. Volatiles were removed in vacuo and the residue was taken up in 200 ml of ethyl acetate, washed twice with 100 ml each of water, and then with a saturated sodium chloride solution (100 ml). The organic phase was dried with magnesium sulfate, filtered and concentrated in vacuo, to give a brown solid. The product was purified by flash chromatography on silica gel (gradient 50%-75% ethyl acetate/hexanes) to yield 4.436 g of a tan solid (65%). M.p.=175° C.; 300 MHz 1H NMR (CDCl3) δ: 8.06 (s, 1H), 8.04 (s, 1H), 7.65-7.60 (m, 2H), 7.48 (d, J=1.6 Hz, 1H), 7.17-7.13 (m, 2H), 6.52 (d, J=5.6 Hz, 1H), 5.1 (br. s, 1H), 4.2-3.9 (m, 3H), 2.2-2.0 9M, 2H), 16.-1.4 (m, 4H), 1.48 (s, 9H). LCMS: 479 [M+H]; calc. for C25H27FN6O3.0.25H2O: C, 62.11; H, 5.74; N, 17.39. Found C, 62.43; H, 5.37; N, 17.35.

Provenance & Evidence