Hydrochloric Acid → N-[2-Methoxy-5-(3-{2-[(2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)amino]pyrimidin-4-yl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]-2-(2-thienyl)acetamide

Beteiligte Stoffe

Reaktionsbedingungen

Reaktionsschritte

To a solution of N-{5-[3-(2-chloropyrimidin-4-yl)pyrazolo[1,5-a]pyridin-2-yl]-2-methoxyphenyl}-2-(2-thienyl)acetamide (110 mg, 0.23 mmol) (see Example 48, step F) in anhydrous i-PrOH (3 mL) was added 2-methyl-1,2,3,4-tetrahydroisoquinolin-7-amine (39 mg, 0.24 mmol), followed by catalytic 12M HCl. After heating for 10 min in the microwave at 180° C., the reaction was quenched with saturated NaHCO3 (25 mL), the solvent removed by rotary evaporation, and the aqueous layer extracted with DCM (25 mL). The organic layer was concentrated and purified by column chromatography (1-10% MeOH in DCM) to provide the product (74 mg, 53%) as a yellow solid. 1H NMR (400 MHz, CDCl3) δ 2.28 (s, 3H), 2.53-2.55 (m, 2H), 2.70-2.72 (m, 2H), 3.36 (s, 2H), 3.87 (s, 3H), 3.97 (s, 2H), 6.49 (d, 1H, J=5.1 Hz), 6.94-6.95 (m, 2H), 7.05-7.13 (m, 2H), 7.25-7.27 (d, 1H, J=8.1 Hz), 7.35-7.43 (m, 3H), 7.48 (s, 1H), 8.19 (d, 1H, J=5.3 Hz), 8.31 (s, 1H), 8.43 (d, 1H, J=8.6 Hz), 8.78 (d, 1H, J=6.8 Hz) 9.38 (s, 1H), 9.45 (s, 1H) ppm. ES-LC/MS m/z=602 [M+H]+.

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