反应详情

温度

100 °C

An oven-dried, nitrogen cooled 5 ml microwave vial was charged with (R)-1-(7-chloro-3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea (Example 571, 78.7 mg, 0.193 mmol), palladium (II) acetate (8.5 mg, 0.038 mmol) and tricyclohexylphosphonium tetrafluoroborate (36 mg, 0.098 mmol), sealed under a nitrogen atmosphere and charged with Dioxane (1.0 ml) and NMP (0.25 ml) followed by dropwise addition of dimethylzinc in toluene (1.6 ml, 1.920 mmol). Heated to 100° C. for 17 hr. Quenched with TFA until gas evolution ceased, and then poured into saturated aqueous sodium bicarbonate. Extracted 3× with DCM and filtered aqueous layer to remove precipitate. Extracted precipitate with DCM/MeOH. Concentrated combined organic extracts in vacuo and purified via flash chromatography (0-20% MeOH/DCM) followed by mass-triggered reverse-phase HPLC. Obtained (R)-1-(7-methyl-3-(2-methylpyridin-4-yl)-1H-pyrazolo[4,3-c]pyridin-6-yl)-3-(1-phenylethyl)urea (26.9 mg, 0.070 mmol, 36.0% yield) as a white solid. MS ESI calc'd for C22H22N6O [M+H]+=387, found 387. 1H NMR (500 MHz, DMSO-d6) δ 936 (br s, 1H), 9.16 (s, 1H), 8.52 (d, J=5.1 Hz, 1H), 8.27 (s, 1H), 7.89 (s, 1H), 7.82 (d, J=5.1 Hz, 1H), 7.37 (m, 4H), 7.21 (m, 1H), 4.97 (m, 1H), 2.56 (s, 3H), 2.48 (s, 1H), 1.45 (d, J=7.1 Hz, 3H).

1. temperatureAn oven-dried, nitrogen cooled 5 ml microwave vial
2. customsealed under a nitrogen atmosphere
3. customQuenched with TFA until gas evolution
4. additionpoured into saturated aqueous sodium bicarbonate
5. extractionExtracted 3× with DCM
6. filtrationfiltered aqueous layer
7. customto remove precipitate
8. extractionExtracted precipitate with DCM/MeOH
9. concentrationConcentrated
10. custompurified via flash chromatography (0-20% MeOH/DCM)