Cesium carbonate → (+/-)-{3-[{1-[3-(4-Fluorobenzyl)-4-oxo-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl]-propyl}-(4-methylbenzoyl)-amino]-propyl}-carbamic acid tert-butyl ester

Participants

Reaction Conditions

Reaction Steps

A mixture of (±)-(3-{(4-methylbenzoyl)-[1-(4-oxo-3,4-dihydropyrrolo[2,1-f][1,2,4] triazin-2-yl)-propyl]-amino}-propyl)-carbamic acid tert-butyl ester (Example 3 A, 38 mg, 0.08 mmol) and cesium carbonate (40 mg, 0.12 mmol) in dioxane (1 mL) was stirred at 40° C., under Ar, for 45 min. To the mixture was added 4-fluorobenzyl bromide (22 mg, 0.12 mmol) and the reaction mixture was stirred at 40° C. for 24 h before being diluted with ethyl acetate. The ethyl acetate layer was washed twice with water and once with brine, before being dried over anhydrous magnesium sulfate and concentrated in vacuo. The crude product was purified by preparative HPLC (YMC S10 ODS, 30×500 mm, 30 minute gradient from 74–90% aqueous methanol with 0.1% TFA). The appropriate fractions were combined, neutralized with saturated aqueous sodium bicarbonate, and then concentrated in vacuo to remove methanol. The mixture was extracted with ethyl acetate (3×10 mL). The combined organic layers were washed once each with water and brine, dried over anhydrous magnesium sulfate, and concentrated in vacuo to yield the title compound (7 mg, 15%): 1H NMR (CDCl3) δ 7.44–6.99 (m, 10H), 6.61 (m, 1H), 5.91 (m, 1H), 5.88 (m, 1H), 4.83 (m, 1H), 3.86 (m, 1H), 3.33 (m, 2H), 2.71 (m, 2H), 2.39 (s, 3H), 2.05 (m, 1H), 1.85 (m, 1H), 1.62 (m, 2H), 1.39 (s, 9H), 0.71 (m, 3H); MS (ESI+), 576.17 (M++H).

Provenance & Evidence