Hydrochloric Acid → N-{3-[3-(2-{[2-(Dimethylamino)-2,3-dihydro-1H-inden-5-yl]amino}pyrimidin-4-yl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(2-thienyl)acetamide

Participants

Reaction Conditions

Reaction Steps

The title compound was synthesized by combining N-{3-[3-(2-chloro-4-pyrimidinyl)pyrazolo[1,5-a]pyridin-2-yl]phenyl}-2-(2-thienyl)acetamide (147 mg, 0.33 mmol) (see Example 2, step B) and (5-amino-2,3-dihydro-1H-inden-2-yl)dimethylamine (70 mg, 0.40 mmol) in i-PrOH (2 mL) and adding 1M hydrochloric acid in diethyl ether (33 uL, 0.03 mmol). The reaction was heated to 180° C. in the microwave for 20 min. repeatedly until LC/MS analysis of the reaction mixture showed consumption of starting material. The reaction product was concentrated to a residue, partitioned between chloroform and saturated aqueous NaHCO3 and the organic fraction was washed with brine. The crude organic solution was dried with Na2SO4 and concentrated. The crude product was purified by silica gel flash column chromatography (DCM: 0-100% 90:9:1 DCM:MeOH:NH4OH(aq)). Purification yielded 43 mg (22%) of a brown powder. 1H NMR (400 MHz, DMSO-d6) δ 10.34 (s, 1H), 9.41 (s, 1H), 8.81 (d, J=6.9 Hz, 1H), 8.46 (m, 1H), 8.21 (dd, J=5.2, 4.1 Hz, 1H), 7.90-7.87 (m, 1H), 7.73 (d, J=8.0 Hz, 1H), 7.64 (d, J=15.4 Hz, 1H), 7.48-7.35 (m, 4H), 7.25 (d, J=7.7 Hz, 1H), 7.11 (t, J=7.0 Hz, 1H), 7.06-7.02 (m, 1H), 6.97-6.94 (m, 1H), 6.45 (dd, J=8.6, 5.4 Hz, 1H), 3.86 (s, 2H), 3.30 (s, 6H), 3.02-2.86 (m, 2H), 2.70-2.63 (m, 1H), 2.17 (s, 2H). ES-LC/MS m/z=586 [M+H]+.

Provenance & Evidence