4-Chlorobenzoyl chloride → (+/-)-(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

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Reaction Steps

A mixture of {3-[[1-(3-benzyl-4-oxo-3,4-dihydropyrrolo[2,1-f][1,2,4]triazin-2-yl)-propyl]-(4-methylbenzoyl)-amino]-propyl}-carbamic acid tert-butyl ester (115 mg, 0.21 mmol, prepared using an identical synthetic sequence to that outlined for Example 12 A–F, except substituting p-toluoyl chloride for 4-chlorobenzoyl chloride in F) and Pd(OH)2 (20 wt. % Pd on carbon, 66 mg) in ethanol (6 mL) was stirred at 50° C., under 60 psi of hydrogen, for 22 h. The catalyst was filtered off and the residue was purified by preparative HPLC (YMC S10 ODS, 30×500 mm, 30 minute gradient from 62–90% aqueous methanol with 0.1% TFA). The appropriate fractions were combined, neutralized with saturated aqueous sodium bicarbonate, and then concentrated in vacuo to remove the 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 (63 mg, 65%): 1H NMR (CDCl3) δ 10.52 (s, 1H), 7.37–7.35 (m, 3H), 7.27–7.23 (m, 2H), 7.07 (m, 1H), 6.54 (m, 1H), 4.60 (m, 1H), 4.21 (m, 1H), 3.40 (m, 2H), 2.89 (m, 2H), 2.40 (s, 3H), 2.29 (m, 2H), 1.64 (m, 2H), 1.37 (s, 9H), 1.08 (t, 3H, J=7.15 Hz); MS (ESI+) 468.21 (M++H).

Provenance & Evidence