2-Methyl-1,2,3,4-tetrahydroisoquinolin-7-amine → 2,2,2-Trifluoro-N-[3-(3-{2-[(2-methyl-1,2,3,4-tetrahydro-7-isoquinolinyl)amino]-4-pyrimidinyl}pyrazolo[1,5-a]pyridin-2-yl)phenyl]acetamide

Participants

Reaction Conditions

Reaction Steps

To a suspension of N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2,2,2-trifluoroacetamide (310 mg, 0.74 mmol, which may be prepared according to Example 11, Step C) and 2-methyl-1,2,3,4-tetrahydro-7-isoquinolinamine (150 mg, 0.92 mmol) in 2-propanol (10 mL) was added 6 drops concentrated HCl. The reaction was stirred for 18 h at 80° C., then partitioned between saturated aqueous NaHCO3 and 20% (v/v) MeOH in EtOAc. The aqueous layer was extracted with 20% (v/v) MeOH in EtOAc, and the combined organic layers were dried over Na2SO4, filtered, and adsorbed onto silica. The crude product was purified by column chromatography to generate the title compound in 72% yield (290 mg, 0.53 mmol). 1H NMR (400 MHz, d6-DMSO) δ 11.39 (s, 1H), 9.45 (s, 1H), 8.85 (d, J=7.0 Hz, 1H), 8.44 (d, J=8.6 Hz, 1H), 8.27 (d, J=5.1 Hz, 1H), 8.02 (s, 1H), 7.83 (d, J=8.6 Hz, 1H), 7.44-7.55 (m, 4H), 7.38 (d, J=8.2 Hz, 1H), 7.14 (t, J=6.9 Hz, 1H), 6.97 (d, J=8.4 Hz, 1H), 6.50 (d, J=5.3 Hz, 1H), 3.39 (s, 2H), 2.75 (t, J=5.7 Hz, 2H), 2.59 (t, J=5.7 Hz, 2H), 2.32 (s, 3H). MS (ESI) m/z=544 [M+H]+.

Provenance & Evidence