Lithium hydroxide, monohydrate → HCID 66551543, compound

Participants

Reaction Steps

A solution of methyl 4-(1-(7-(3,4-dimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)piperidin-3-ylcarbamoyl)benzoate (250 mg, 0.45 mmol) and LiOH.H2O (191 mg, 4.5 mmol) in 2 mL of water, 12 mL of methanol and 30 mL of THF was stirred at room temperature for 1 hour. The solvent was evaporated and the residue was suspended in 30 mL of THF, then treated with 2N HCl to pH=2. The solvent was evaporated and the residue was dissolved in 50 mL of THF, filtered to remove the salts. The filtrate was evaporated and crude 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: 28% acetonitrile/72% water (0.1% TFA V/V) initially, and then proceed to 50% acetonitrile/50% 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)piperidin-3-ylcarbamoyl)benzoic acid (45 mg, 18.4%) as a solid. 1H NMR (300 MHz, DMSO): δ 13.20 (brs, 1H), 9.63 (s, 1H), 8.85 (s, 1H), 8.04-7.95 (m, 4H), 7.63 (s, 1H), 7.41-7.32 (m, 2H), 6.88-6.85 (m, 1H), 5.34-5.31 (m, 1H), 4.71-4.52 (m, 2H), 3.70 (s, 3H), 3.67 (s, 3H), 3.04-2.97 (m, 2H), 2.04-1.96 (m, 4H). LC-MS: 535 [M+H]+; 532.9 [M−H]−, tR=1.43 min. HPLC: 99.26% at 214 nm, 99.79% at 254 nm, tR=5.37 min.

Provenance & Evidence