5,7-Dichloro-2-Methylthiazolo[4,5-d]pyriMidine synthesis

Yield:859796-00-2 79%

Reaction Conditions:

with trichlorophosphate at 180; for 2 h;

Steps:

1 Example 1. (S)-(5-((1-(5-Fluoropyridin-3-yl)ethyl)amino)-2-methylthiazolo[4,5-d]pyrimidin-7-yl)(pyrrolidin-1-yl)methanone

Synthesis of 5,7-dichloro-2-methylthiazolo[4,5-d]pyrimidine: A solution of 2-methylthiazolo[4,5-d]. A solution of 2-methylthiazolo[4,5-d]pyrimidine-5,7(4H,6H)-dione (3.7 g, 20.2 mmol) (commercially obtained from Ark Pharm, Arlington Heights, IL) in phosphoryl trichloride (40 mL) was stirred for 2 h at 180 °C. The reaction was then quenched by addition of 80 mL of water. The resulting solution was extracted with ethyl acetate and the combined organic layer was dried over anhydrous sodium sulfate and concentrated under vacuum. The residue was purified by flash chromatography on silica gel eluting with 20% ethyl acetate in petroleum ether to provide 5,7-dichloro-2-methylthiazolo[4,5-d]pyrimidine (3.5 g, 79% yield) as an yellow solid. ¹H NMR (400 MHz, DMSO-d₆) δ 3.00 (3H, s) ppm. ESI MS: m/z [M+H⁺] for C₆H₃Cl₂N₃S, calcd 220.0, found 220.0.

References:

EP3616753,2020,A1 Location in patent:Paragraph 0645-0646