Sodium Carbonate → 3-(7-(3,4,5-Trimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzamide

Participants

Reaction Conditions

Reaction Steps

To a stirred solution of 5-chloro-N-(3,4,5-trimethoxyphenyl)thiazolo[5,4-d]pyrimidin-7-amine (337 mg, 0.95 mmol), 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (190 mg, 1.15 mmol) and Na2CO3 (347 mg, 3.27 mmol) in 2 mL of water and 50 mL of dioxane was added Pd(PPh3)4 (100 mg, 0.086 mmol) in one portion at room temperature under nitrogen. Then the mixture was stirred at 97° C. for 16 hours under nitrogen. The solvent was evaporated at 40° C. at reduced pressure and the residue was purified by silica gel chromatography (silica gel 200-300 mesh, eluting with a mixture of petroleum ether and ethyl acetate (1:2)) to give a crude product. It 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.) to give 3-(7-(3,4,5-trimethoxyphenylamino)thiazolo[5,4-d]pyrimidin-5-yl)benzamide (120 mg, 27.4%) as a solid. 1H NMR (300 MHz, DMSO): δ 10.10 (s, 1H), 9.43 (s, 1H), 8.93 (s, 1H), 8.58 (d, 1H, J=8.1 Hz), 8.03-8.00 (m, 2H), 7.65-7.60 (m, 3H), 7.50 (brs, 1H), 3.87 (s, 3H), 3.71 (s, 3H), 3.30 (s, 3H). LC-MS: 438 [M+H]+, tR=1.43 min. HPLC: 99.77% at 214 nm, 99.84% at 254 nm, tR=5.68 min.

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