反应详情

6-chloro-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridine-4-carbaldehyde (Intermediate 11B, 25 g, 55.1 mmol) was dissolved in DCM (100 ml, sonication required) and slowly charged with MeOH (100 ml). The solution was cooled in an ice bath then charged with sodium borohydride (2.60 g, 68.8 mmol) portion wise (exothermic) and allowed to stir for 1 h at RT. A large exotherm was observed and the reaction turned dark red. TLC showed product had formed after 20 minutes. The reaction was diluted with 500 mL DCM and 200 mL water. A large amount of dark red to brick red material was filtered off. The aq. layer was extracted with 1×200 mL DCM and the combined organics were washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo. Purification on silica gel, 0-10% EtOAc/DCM gave (6-chloro-3-methoxy-1-trityl-1H-pyrazolo[4,3-c]pyridin-4-yl)methanol (35B, 15 g, 32.9 mmol, 59.7% yield) as a pale yellow solid. MS: [M+H]+ m/z 456. 1H NMR (500 MHz, CDCl3) δ 7.34-7.27 (m, 10H), 7.23-7.18 (m, 5H), 5.78 (s, 1H), 4.99 (s, 2H), 3.93 (s, 3H), 3.86 (s, 1H).

1. temperatureThe solution was cooled in an ice bath
2. customhad formed after 20 minutes
3. filtrationA large amount of dark red to brick red material was filtered off
4. extractionThe aq. layer was extracted with 1×200 mL DCM
5. washthe combined organics were washed with brine
6. dry with materialdried over sodium sulfate
7. filtrationfiltered
8. concentrationconcentrated in vacuo
9. customPurification on silica gel, 0-10% EtOAc/DCM