3-Iodo-2,5-dimethyl-7-(pentan-3-yl)pyrazolo[1,5-a]pyrimidine → 7-(1-Ethyl-propyl)-2,5-dimethyl-3-(3-methyl-thieno[3,2-b]pyridin-2-yl)-pyrazolo[1,5-a]pyrimidine

Participants

Reaction Conditions

Reaction Steps

Charge an oven dried schrenk flask with 3-methylthieno[3,2-b]pyridine (0.213 g, 1.42 mmol) and anhydrous THF (5 mL) and cool to −78° C. under an inert atmosphere. Add n-butyl lithium (2.5 M hexane, 0.72 mL, 1.78 mmol) and stir at reduced temperature for 30 min. Add anhydrous zinc chloride (0.58 g, 4.26 mmol) in one aliquot and stir 15 min at reduced temperature. Allow the reaction to warm to room temperature and stir an additional 30 min. Dilute the reaction with anhydrous THF (5 mL) and add 7-(1-ethyl-propyl)-3-iodo-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine (0.406 g, 0.08 mmol). Degas 15 min with positive argon pressure and add dichloro[1,1′-bis(diphenylphosphino) ferrocene]palladium (II) dichloromethane (0.093 g, 0.114 mmol). Reflux the reaction overnight in an oil bath (90° C.) under an inert atmosphere. Cool the reaction to room temperature, quench with saturated ammonium chloride, and dilute with ethyl acetate (75 mL). Separate and extract the aqueous portion with ethyl acetate (50 mL). Combine the organic phases, dry over anhydrous magnesium sulfate, filter, and concentrate under reduced pressure. Purify using flash chromatography, eluting with 100% hexane/0% (15% ethyl acetate/hexane) to 0% hexane/100% (15% ethyl acetate/hexane) in a step gradient of 10% increments to give a white foam (0.059 g, 14%). ES/MS m/z 365.0 (M+1)+.

Provenance & Evidence