Pyrazolo[1,5-a]pyrimidine-3-boronic acid pinacol ester synthesis

Yield: 51.4%

Reaction Conditions:

with potassium acetate;bis-triphenylphosphine-palladium(II) chloride in 1,4-dioxane at 20 - 100;

Steps:

2.B; X.c
To a stirred solution of compound 13f (27.8 mmol) in 1,4-dioxane (120 mL) was added B₂Pm₂ (126 mmol) and KOAc (101 mmol) at rt. The resulting mixture was purged with Ar for 45min, PdCl₂(PPli3)₂ (1.5 mmol) was added and the mixture again purged with Ar for 30min. The resulting mixture was heated to 100⁰C for 15h. The reaction mixture was concentrated to obtain a viscous mass, which was charged over afluorosil plug, washed with pentane, followed by 60% EtOAc/Pet ether. The relevant fractions were concentrated to obtain a crude compound 13g as a pale yellow solid. The crude compound 13g was stirred with pentane (25mL) at -40⁰C for 30min, filtered, washed with cold pentane (5mL) and dried under vacuum to obtain sufficiently pure compound (3.5g, 51.4%). TLC system: Ethyl acetate: Petroleum ether (2:3) R_f value: 0.4. (M + H): 246.3.

References:

VERTEX PHARMACEUTICALS INCORPORATED WO2009/85913, 2009, A1 Location in patent:Page/Page column 68; 69-70