Phthalimide → 2-[2-(4-Fluorophenyl)-3-(4-pyridinyl)pyrazolo[1,5-a]pyridin-5-yl]methyl-1H-isoindole-1,3(2H)-dione

Participants

Reaction Conditions

Reaction Steps

2-(4-Fluorophenyl)-5-hydroxymethyl-3-(4-pyridinyl)pyrazolo[1,5-a]pyridine (Example 6. 68 mg, 0.213 mmol), triphenyl phosphine (168 mg, 0.64 mmol) and phthalimide (63 mg, 0.43 mmol) are dissolved in dry THF (3 mL). The stirred solution is cooled to 0° C. and diethyl azodicarboxylate (105 mg of 85% grade, 0.51 mmol) is added dropwise. The solution is stirred at 0° C. for 2 h during which time a white solid deposits and then stirred for 16 h at room temperature. The solution is then diluted with ether (20 mL) and the deposited solid filtered off. The solid is washed with ether and dried to give the first batch of product (20 mg). The ether solution is then washed with water and then extracted with dilute hydrochloric acid. A portion of the product deposits and is filtered off, washed twice with ether and dried to give the product as the hydrochloride salt (16 mg). The acidic phase is washed with ether and then made alkaline with sodium bicarbonate solution. Extraction with ethyl acetate (50 mL×3) followed by drying (MgSO4) and concentration gives the product as an off-white solid (32 mg). 1H NMR (d6-DMSO) δ 4.83 (s, 2H), 6.91 (dd, J=1.8, 7.2 Hz, 1H), 7.22 (t, J=8.9 Hz, 2H), 7.26 (d, J=5.9 Hz, 2H), 7.49 (dd, J=5.6, 8.6 Hz, 2H), 7.71 (s, 1H), 7.81–7.89 (m, 4H), 8.54 (d, J=4.7 Hz, 2H), 8.72 (d, J=7.1 Hz, 1H); APESI-MS m/z 449 (M+1)+

Provenance & Evidence