Lithium hydroxide, monohydrate → HCID 66551542, compound

Participants

Reaction Steps

A solution of methyl 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)benzoate (190 mg, 0.255 mmol) and LiOH.H2O (149 mg, 3.55 mmol) in 2 mL of water, 10 mL of methanol and 15 mL of THF was stirred at room temperature for 2 hours. The solvent was evaporated after the solution was acidified by 2N HCl to pH=2 and the residue was dissolved in 50 mL of THF, filtered to remove the salts. The filtrate 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: 25% acetonitrile/75% 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.) to give 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)pyrrolidin-3-ylcarbamoyl)benzoic acid (86 mg, 46.5%) as a solid. 1H NMR (300 MHz, DMSO): δ 9.63 (s, 1H), 8.36-8.79 (m, 2H), 8.02-7.88 (m, 5H), 7.60-7.50 (m, 1H), 6.93 (d, 1H, J=8.7 Hz), 4.61-4.59 (m, 1H), 3.95-3.66 (m, 10H), 2.28-2.10 (m, 2H). LC-MS: 521 [M+H]+; 518.8 [M−H]−, tR=1.36 min. HPLC: 99.85% at 214 nm, 99.84% at 254 nm, tR=4.67 min.

Provenance & Evidence