Trifluoroacetic acid → 4-(1-(7-(3,4-Dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidine-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)piperidine-3-carboxamido)benzoate (75 mg, 0.127 mmol) in 5 mL of DCM was added TFA (2 mL) dropwise at room temperature. Then the reaction mixture was stirred at room temperature for 24 hours. The solvent was evaporated at 40° 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 55% acetonitrile/45% 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)piperidine-3-carboxamido)benzoic acid (25 mg, 36.8%) as a white solid. 1H NMR (300 MHz, CD3OD): δ 8.71 (s, 1H), 7.99-7.96 (m, 2H), 7.68-7.65 (m, 2H), 7.51 (s, 1H), 7.27-7.23 (m, 1H), 6.86 (d, 1H, J=8.4 Hz), 3.79 (s, 3H), 3.70 (s, 3H), 2.67 (brs, 3H), 2.19-1.87 (m, 6H). LC-MS: 535 [M+H]+; 533 [M−H]−, tR=1.47 min. HPLC: 96.74% at 214 nm, 97.85% at 254 nm, tR=5.46 min.

Provenance & Evidence