tert-butyl 3-(7-chloropyrazolo[1,5-a]pyrimidin-5-yl)piperidine-1-carboxylate synthesis

Yield:877173-81-4 71%

Reaction Conditions:

with trichlorophosphate in N,N-dimethyl-aniline at 25; for 96 h;Product distribution / selectivity;

Steps:

19; X-30-C

A mixture of the product from Preparative Example 2 (12.50 g, 39.3 mmol), N,N-dimethylaniline (15.5 mL), and POCl₃ (125 mL) was stirred at 25° C. for 4 days. Excess of POCl₃ was evaporated and the residue was poured into saturated aqueous NaHCO₃ (600 mL). The mixture was extracted with CH₂Cl₂ (3×200 mL), the combined extracts were dried over Na₂SO₄, filtered, and the solvent was evaporated. The residue was purified by column chromatography on silica gel with 8:1 CH₂Cl₂/EtOAc as eluent. Pale yellow wax (9.41 g, 71%) was obtained. LC-MS: 337 [M+].; PREPARATIVE EXAMPLE X-30-C A mixture of the product from Preparative Example X-20-C (12.50 g, 39.3 mmol), N,N-dimethylaniline (15.5 mL), and POCl₃ (125 mL) was stirred at 25° C. for 4 days. Excess of POCl₃ was evaporated and the residue was poured into saturated aqueous NaHCO₃ (600 mL). The mixture was extracted with CH₂Cl₂ (3×200 mL), the combined extracts were dried over Na₂SO₄, filtered, and the solvent was evaporated. The residue was purified by column chromatography on silica gel with 8:1 CH₂Cl₂/EtOAc as eluent. Pale yellow wax (9.41 g, 71%) was obtained. LC-MS: 337 [M+].

References:

US2007/82900,2007,A1 Location in patent:Page/Page column 98; 113