Dichloromethane → Hydrochloric Acid

Participants

Reaction Steps

To a stirred solution of 4-{3-[7-(3,4-dimethoxy-phenylamino)-thiazolo[5,4-d]pyrimidin-5-yl]-benzoyl}-[1,4]-diazepane-1-carboxylic acid tert-butyl ester (130 mg, 0.22 mmol) in 10 mL of CH2Cl2 was added slowly CF3COOH (4 mL) at room temperature. Then the mixture was stirred at room temperature for 16 hours. The solvent was evaporated 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: 20% acetonitrile/80% water (0.1% TFA V/V) initially, and then proceed to 45% acetonitrile/55% water (0.1% TFA V/V) in a linear fashion after just 9 min.), then 1M HCl (0.5 mL) was added and stirred, then solvents were removed under reduced pressure to give [1,4]diazepan-1-yl-{3-[7-(3,4-dimethoxy-phenylamino)-thiazolo[5,4-d]pyrimidin-5-yl]-phenyl}-methanone as HCl salt (35 mg, 30.2%) as a yellow solid. 1H NMR (300 MHz, DMSO): δ 10.18 (s, 1H), 9.38 (s, 1H), 9.05 (brs, 2H), 8.46-8.44 (m, 2H), 7.86 (s, 1H), 7.60-7.59 (m, 2H), 7.42 (dd, 1H, J1=8.7 Hz, J2=2.7 Hz), 6.99 (d, 1H, J=8.7 Hz), 3.85 (brs, 2H), 3.80 (s, 3H), 3.77 (s, 3H), 3.44 (brs, 2H), 3.30 (brs, 2H), 3.20 (brs, 2H), 2.02-1.96 (m, 2H). LC-MS: 491.2 [M+H]+, tR=1.51 min. HPLC: 99.24% at 214 nm, 98.23% at 254 nm, tR=4.65 min.

Provenance & Evidence