Reaktion #505348

Reaktionsgleichung

7-chloro-5-(4-chloro-phenyl)-pyrazolo[1,5-a]pyrimidine

cyclopropylmagnesium bromide THF

ammonium chloride

cyclopropylzinc chloride THF

→

title compound

5-(4-Chloro-phenyl)-7-cyclopropyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid

Lösungsmittel

THF

Reaktionsbedingungen

Aufarbeitung

1. 1
   Sonstigefreshly prepared
2. 2
   Temperatur) and the mixture was refluxed in an atmosphere of argon for 2.5 h
3. 3
   Sonstigethe mixture was partitioned between ethyl acetate and 10% sodium chloride solution
4. 4
   SonstigeThe organic layer was evaporated in vacuo
5. 5
   Sonstigethe residue chromatographed on silica gel
6. 6
   Sonstigeto give
7. 7
   Sonstigeafter crystallization from ethyl acetate ethyl 5-(4-chloro-phenyl)-7-cyclopropyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (2.54 g, 62%) as an off-white solid, mp 141-143° C

Vorschrift

To a solution of 7-chloro-5-(4-chloro-phenyl)-pyrazolo[1,5-a]pyrimidine (4.0 g, 12.0 mmol), tetrakis(triphenylphosphin)palladium (1.15 g, 1.0 mmol) in THF (20 mL) was added at 20° C. 0.25 M cyclopropylzinc chloride/THF suspension (ca.192 mL, 48 mol; freshly prepared by stirring a mixture of 96 mL of 0.5 M cyclopropylmagnesium bromide/THF and 96 mL of 0.5 M zinc chloride/THF (96 mL) for 1 h at 0° C. followed by 1 h at 20° C.) and the mixture was refluxed in an atmosphere of argon for 2.5 h. After the slow addition at 0° C. of sat. aqueous ammonium chloride solution (30 mL), the mixture was partitioned between ethyl acetate and 10% sodium chloride solution. The organic layer was evaporated in vacuo and the residue chromatographed on silica gel using ethyl acetate/cyclohexane (1:4 v/v) as eluent to give after crystallization from ethyl acetate ethyl 5-(4-chloro-phenyl)-7-cyclopropyl-pyrazolo[1,5-a]pyrimidine-3-carboxylic acid (2.54 g, 62%) as an off-white solid, mp 141-143° C. This material was saponified using in an analogous manner the procedure described in example C.22, step d), to give the title compound. Off-white solid, MS (ISN) 312.3 [(M−H)−]; mp 242-243° C.

Quelle