Bis-(1H-imidazol-2-YL)-methanone → (+/-)-Methyl 2-(4-(8-fluoro-1,2-dihydro-2-oxoquinazolin-3(4H)-yl)piperidine-1-carboxamido)-3-(7-methyl-1H-indazol-5-yl)propanoate

Participants

Reaction Conditions

Reaction Steps

A stirred solution of 2-amino-3-(7-methyl-1H-indazol-5-yl)-propionic acid methyl ester (0.36 g, 1.54 mmol) in tetrahydrofuran (15 mL) at 0° C. was treated with carbonyl diimidazole (0.20, 1.1 equiv). The reaction was stirred for min at 0° C., warmed to room temperature, stirred 10 min, and treated with 8-fluoro-3,4-dihydro-3-(piperidin-4-yl)quinazolin-2(1H)-one (0.38 g, 1.1 equiv). The mixture was stirred at room temperature overnight. The solvent was evaporated and the residue purified by column chromatography to give 0.41 g (53%) as a white powder. 1H-NMR (CDCl3, 500 MHz) δ 1.53-1.68 (m, 4H), 2.48 (s, 3H), 2.82 (m, 2H), 3.05 (m, 6H), 3.09 (dd, JAB=13.7, 6.1, 1H), 3.14 (dd, JAB=140.0, 6.1, 1H), 3.35 (bs, 1H), 3.68 (s, 3H), 3.88-4.02 (m, 2H), 4.22 (d, JAB=15.6, 1H), 4.25 (d, JAB=15.3, 1H), 4.44 (m, 1H), 4.71 (dd, J=6.1, 6.1, 1H), 6.78 (d, J=7.3, 1H), 6.84 (ddd, J=7.6, 7.6, 4.9, 1H), 6.88-6.95 (m, 2H), 7.28 (s, 1H), 7.91 (s, 1H). Mass spec.: 509.25 (MH)+.

Provenance & Evidence