Phosphorus oxybromide → HCID 178468567, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 6-hydroxy-3-methyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester (13.7 g) and phosphorous oxybromide (19.5 g) in toluene (300 mL) was stirred at 110° C. for 5 h, cooled to r.t., and added dropwise into an ice cold solution of potassium acetate (18.2 g) in water (300 mL). The mixture was extracted twice with ethyl acetate, the combined organic phases were washed with brine, dried over magnesium sulfate and concentrated in a membrane pump vacuum. 6-Bromo-3-methyl-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester (4.6 g, 26% yield) was obtained. This material was dissolved in THF (60 mL), and 3,4-dihydro-2H-pyran (1.6 mL) and p-toluenesulfonic acid monohydrate (0.91 g) was added. The solution was stirred at r.t. for 48 h, then 3,4-dihydro-2H-pyran (1.6 mL) was added and the solution stirred again for 48 h. The mixture was poured into water and extracted with ethyl acetate, the organic layer was dried over magnesium sulfate and concentrated in a membrane pump vacuum. The residue was purified by flash chromatography (silica, heptane/ethyl acetate gradient). 6-Bromo-3-methyl-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-b]pyridine-4-carboxylic acid ethyl ester (2.2 g, 38%) was obtained.

Provenance & Evidence