Sodium Hydroxide → 3-Bromo-5-chloropyrazolo(1,5-a)pyrimidine

Participants

Reaction Steps

Sodium acetate [127-09-3] (24.1 g, 293.9 mmol) was added to a solution of 5-chloro-pyrazolo[1,5-a]pyrimidine [29274-24-6], (30.1 g, 195.7 mmol) in glacial acetic acid (395 mL) and allowed to stir at ambient temperature until all of the solid had dissolved. An ice bath was then put in place, and the solution chilled to 0° C. Bromine [7726-95-6] (11.0 mL, 214.7 mmol) was added drop by drop into the 0° C. buffered acetic acid reaction solution over 35 minutes which gradually became a thick stirred suspension. Upon completion of the bromine addition, the suspension was allowed to stir for a further 15 minutes then was slowly poured into an aqueous (5% w/v) solution (1 L) of sodium metabisulfite [7681-57-4] stirred in an ice bath. Solid sodium hydroxide [1310-73-2] pellets were added to the stirred suspension, at a rate to maintain an internal temperature of less than 40° C., until pH of the supernatant was determined to be approximately 8 by pH paper. Precipitated product was isolated by filtration, the filter cake washed with water, and allowed to dry to afford 39.8 g of light yellow powder, mp. 173-174° C. 1H NMR (400 MHz, DMSO-d6) δ ppm 7.22 (d, J=7.33 Hz, 1H) 8.44 (s, 1 H) 9.21 (d, J=7.07 Hz, 1 H). 13C NMR (100 MHz, DMSO-d6) δ ppm 82.84, 109.99, 138.94, 143.76, 145.61, 151.18. LRMS (ESI) m/z 231.8/233.8/235.8 [(M+H)]+, calc'd for C6H3BrClN3: 232.47.

Provenance & Evidence