Trifluoroacetic acid → 4-(1-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidine-3-carboxamido)benzoic acid

Participants

Reaction Steps

To a stirred solution of tert-butyl 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidine-3-carboxamido)benzoate (105 mg, 0.18 mmol) in 10 mL of dichloromethane was added trifluoroacetic acid (5 mL) in one portion at room temperature. Then the reaction mixture was stirred at this temperature for 24 hours. The solvent was evaporated at 37° C. at reduced pressure and the residue was purified by preparative HPLC (Gemini 5u C18 150×21.2 mm; inject volume: 3 ml/inj, flow rate: 20 ml/min; wavelength: 214 nm and 254 nm; the gradient conditions are: 30% acetonitrile/70% water (0.1% TFA V/V) initially, and then proceed to 60% acetonitrile/40% water (0.1% TFA V/V) in a linear fashion after just 9 min.) to give 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidine-3-carboxamido)benzoic acid (56 mg, 59%) as a white solid. 1H NMR (300 MHz, DMSO): δ 10.42 (s, 1H), 9.64 (s, 1H), 8.84 (s, 1H), 7.92-7.73 (m, 6H), 7.48 (brs, 1H), 6.93 (d, 1H, J=9.0 Hz), 3.92-3.36 (m, 11H), 2.29-2.21 (m, 2H). LC-MS: 521 [M+H]+, tR=1.38 min. HPLC: 99.34% at 214 nm, 99.25% at 254 nm, tR=4.75 min.

Provenance & Evidence