Ammonium Chloride → 7-(1-Propyl-butyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine

Participants

Reaction Conditions

Reaction Steps

Heat a mixture of magnesium turnings (3.5 g, 144 mmol) and a catalytic amount of iodine (100 mg) in THF (100 mL) to 65° C. under a nitrogen atmosphere. Add a few drops of neat 4-bromoheptane and heat the mixture until the reaction starts. Then add a solution of 4-bromoheptane (17.6 mL, 94 9 mmol) in THF (42 mL) keeping the temperature at 65-70° C. over 2 h. Reflux the mixture for an additional hour and then cool the reaction to 22° C. Add the prepared Grignard reagent to a solution of 7-chloro-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine (10.2 g; 53 3 mmol) in THF (60 mL) cooled to 0° C. under a nitrogen atmosphere. Add the magnesium reagent solution via cannula over 45 min while keeping the temperature below 10° C. Then stir the mixture for an additional 30 min at 5° C. Add to this mixture a 10% aqueous ammonium chloride solution (wt/wt) (125 mL) and stir at 22° C. for 30 min. Separate the organic layer and extract the aqueous layer with ethyl acetate (2×25 mL). Combine the organic layers and dry over sodium sulfate. Filter the mixture and evaporate the solvent. Purify the crude material by silica gel flash chromatography using an eluent of hexanes/ethyl acetate (5/1) to provide the title compound (8 g, 62%). ES/MS m/z 246 (M+1)+.

Provenance & Evidence