Hydrochloric Acid → 2-(5-Bromo-2-(4-methoxyphenyl)pyrazolo[1,5-a]pyridin-3-yl)acetaldehyde

HRID 1475958Notes

Reaction equation

[Br:1][C:2]1[CH:7]=[CH:6][N:5]2[N:8]=[C:9]([C:15]3[CH:20]=[CH:19][C:18]([O:21][CH3:22])=[CH:17][CH:16]=3)[C:10]([CH:11]=[CH:12][O:13]C)=[C:4]2[CH:3]=1.Cl.O>C1COCC1>[Br:1][C:2]1[CH:7]=[CH:6][N:5]2[N:8]=[C:9]([C:15]3[CH:16]=[CH:17][C:18]([O:21][CH3:22])=[CH:19][CH:20]=3)[C:10]([CH2:11][CH:12]=[O:13])=[C:4]2[CH:3]=1

Participants

Conditions

Temperature: 50 °C

Procedure

To a stirred solution of 5-bromo-2-(4-methoxyphenyl)-3-(2-methoxyvinyl)pyrazolo[1,5-a]pyridine (160 mg, 0.45 mmol) in THF (7.3 ml) was added a 4N HCl solution in water (2.45 ml, 9.8 mmol). Heated to 50° C. and stirred for 4 h at which time monitoring the reaction by LC indicated all starting material had converted to the title compound. The solution was cooled to 20° C. and a saturated solution of sodium bicarbonate (10 mL) and ethyl acetate (15 mL) were added The organic layer was dried over anhydrous MgSO4, filtered and concentrated to dryness to afford a residue that was purified by automated ISCO chromatography (ethyl acetate/dichloromethane; 7/93). The title compound was obtained as a tan solid (43 mg, 28%). LCMS m/z 345.0, 347.0 (M+H)+, ret. time=2.02, 2.12 min. Peak at 2.01 is hydrate of the aldehyde LCMS m/z 363.1, 365.1 (M+H)+ and peak at 2.12 is methyl hemiacetal of the aldehyde LCMS m/z 377.1, 379.1 (M+H)+ both formed under LCMS conditions.

Workup

customthe reaction by LC

Sources & evidence

ORD record: ord-391d790e015b473e89c6882ddce2e504
Source dataset: uspto-grants-2015_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09018395B2

Reaction notes

Loading…