Cyclopentylamine → N-cyclopentyl-2-(4-fluorophenyl)-3-[2-(1-pyrrolid inyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-alpha]pyridin-7-amine

Participants

Reaction Steps

To a solution of 7-chloro-2-(4-fluorophenyl)-3-[2-(1-pyrrolidinyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-a]pyridine (54 mg, 0.12 mmol) in toluene (3 mL) was added successively racemic-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (9.2 mg, 0.013 mmol), cesium carbonate (57 mg, 0.17 mmol), cyclopentylamine (0.5 mL, 5.0 mmol), and palladium (II) acetate (2 mg, 0.009 mmol). The resultant mixture was heated at 85° C. for 6 hours at which time the reaction was judged complete by thin layer chromatography. The solution was cooled to room temperature and ether was added. The organic layer was washed with water and brine. The aqueous layer was extracted with ether and the combined organics dried over magnesium sulfate. Filtration and concentration followed by flash chromatography (12:1 to 8:1 hexanes-ethyl acetate) provided N-cyclopentyl-2-(4-fluorophenyl)-3-[2-(1-pyrrolidinyl)-4-pyrimidinyl]-6-(trifluoromethyl)pyrazolo[1,5-a]pyridin-7-amine (37 mg, 63%) as an oil. 1H NMR (CDCl3): δ 8.16 (d, 1 H), 7.84 (d, 1 H), 7.68 (dd, 2 H), 7.49 (d, 1 H), 7.18 (t, 2 H), 6.55 (d, 1 H), 6.29 (d, 1 H), 4.57 (m, 1 H), 3.68 (m, 4 H), 2.13–2.05 (m, 6 H), 1.84–1.65 (m, 6 H); 19F NMR (CDCl3) δ −55.33, −112.78; MS m/z 511 (M+1). This material was taken up in ether and treated with hydrochloric acid in ether to yield a bright yellow powder which was isolated by filtration as a hydrochloride salt.

Provenance & Evidence