反应详情

2-(4-Fluorophenyl)-5-hydroxymethyl-3-(4-pyridinyl)pyrazolo[1,5-a]pyridine (Example 6. 30 mg, 0.094 mmol) and 4-pyridinecarboxylic acid (0.12 mmol) are dissolved in dimethylformamide (0.5 mL) and diethyl cyanophosphonate (35 mg, 0.2 mmol, 93% grade), followed by triethylamine (35 mg, 0.35 mmol) are added dropwise. The resulting solution is stirred at room temperature until the reaction is complete as determined by TLC and then diluted with hexane/ethyl acetate (30 mL of a 1:1 mixture) and washed with water (3×). The organic phase is then shaken with dilute hydrochloric acid. In cases were the hydrochloride salt of the product deposits at this stage it is filtered off, washed with water and then hexane and dried. If no deposit is observed, the acidic phase is separated, washed once with hexane/ethyl acetate (15 mL of a 1:1 mixture) and basified with saturated sodium bicarbonate solution. This is then extracted with dichloromethane (15 mL) five times and the dichloromethane solution dried (MgSO4), filtered and concentrated to give the title compound. 1H NMR (d6-DMSO) δ 5.43 (s, 2H), 7.15 (d, J=6.9 Hz, 1H), 7.25 (t, J=8.8 Hz, 2H), 7.30 (d, J=5.9 Hz, 2H), 7.50–7.53 (m, 2H), 7.84–7.87 (m, 3H), 8.55 (d, J=5.7 Hz, 2H), 8.79 (d, J=5.9 Hz, 2H), 8.82 (d, J=7.1 Hz, 1H); APESI-MS m/z 425 (M+1)+.

1. additionare added dropwise
2. washwashed with water (3×)
3. stirringThe organic phase is then shaken with dilute hydrochloric acid
4. filtrationis filtered off
5. washwashed with water
6. dry with materialhexane and dried
7. customthe acidic phase is separated
8. washwashed once with hexane/ethyl acetate (15 mL of a 1:1 mixture) and
9. extractionThis is then extracted with dichloromethane (15 mL) five times
10. dry with materialthe dichloromethane solution dried (MgSO4)
11. filtrationfiltered
12. concentrationconcentrated