Pivalic acid → HCID 178458935, compound

Participants

Reaction Conditions

Reaction Steps

6-Bromo-N-(4-cyclopropylpyridin-2-yl)-4-methylpyridin-2-amine (263 mg, 0.865 mmol), trans-methyl 4-[1-hydroxy-1-(1,3-thiazol-2-yl)propyl]cyclohexanecarboxylate (245 mg, 0.865 mmol), pivalic acid (151 μl, 1.297 mmol), potassium carbonate (358 mg, 2.59 mmol), π-allyl palladium(II)chloride dimer (31.6 mg, 0.086 mmol) and butyl di-1-adamantylphosphine (124 mg, 0.346 mmol) were combined and the reaction flask was put under inert atmosphere (3× vacuum/argon cycle) then degassed dimethylacetamide (2 mL) was added. The reaction was heated to 100° C. for 5 hours, then cooled to room temperature and poured into diethyl ether (100 mL). The resulting solution was transferred to a separatory funnel and sequentially washed with water (3×50 mL) and sodium bicarbonate (50 mL), dried over magnesium sulfate, filtered and concentrated under reduced pressure. The resulting crude oil was purified by silica gel chromatography (0-100% ethyl acetate/hexanes) to afford methyl trans-4-[l-(5-{6-[(4-cyclopropylpyridin-2-yl)amino]-4-methylpyridin-2-yl}-1,3-thiazol-2-yl)-1-hydroxypropyl]cyclohexanecarboxylate as a yellow foam. MS ESI calc'd. for C28H35N4O3S [M+H]+ 507. found 507. 1H NMR (500 MHz, CDCl3) δ 8.12-8.04 (m, 2H), 7.71 (s, 1H), 7.23 (s, 1H), 7.05 (s, 1H), 6.86 (s, 1H), 6.66 (d, J=5.2 Hz, 1H), 3.64 (s, 3H), 2.35 (s, 3H), 2.28-2.16 (m, 1H), 2.16-1.86 (m, 811), 1.51-1.30 (m, 3H), 1.26 (t, J=7.1 Hz, 1H), 1.21-1.06 (m, 3H), 1.03-0.93 (m, 2H), 0.83 (t, J=7.2 Hz, 3H).

Provenance & Evidence