(2Z)-3-(dimethylamino)-2-fluoro-1-(1-isopropyl-2-methyl-1H-imidazol-5-yl)prop-2-en-1-one → (R)-1-{4-[5-Fluoro-4-(3-isopropyl-2-methyl-3H-imidazol-4-yl)-pyrimidin-2-ylamino]-phenyl}-pyrrolidine-2-carboxylic acid methylamide

Participants

Reaction Conditions

Reaction Steps

(R)-1-(4-Guanidino-phenyl)-pyrrolidine-2-carboxylic acid methylamide (Method 59; 0.22 g, 0.82 mmol) and (2Z)-3-(dimethylamino)-2-fluoro-1-(1-isopropyl-2-methyl-1H-imidazol-5-yl)prop-2-en-1-one (Method 14; 0.15 g, 0.63 mmol) were added to 2-methoxyethanol (4 ml) and heated at 200° C. for 2 hours in the microwave. Solvent was removed in vacuo and chromatographed. The product was passed purified by HPLC, and the required fractions were combined and basified with K2CO3 (0.5 g), extracted with DCM (2×50 ml), dried and solvent removed in vacuo to yield a yellow solid (110 mg, 40%). NMR (400.132 MHz, CDCl3) 8.21 (d, 1H), 7.56 (d, 1H), 7.34 (d, 2H), 6.79 (s, 1H), 6.60 (d, 2H), 6.56 (s, 1H), 5.56 (septet, 1H), 3.99 (t, 1H), 3.64 (t, 1H), 3.20 (q, 1H), 2.80 (d, 3H), 2.58 (s, 3H), 2.29-2.24 (m, 2H), 2.06-1.89 (m, 2H), 1.45 (d, 6H); m/z 438.

Provenance & Evidence