Bromide ion → HCID 45138156, compound

Temperature

130 °C

To a microwave tube charged with 1-(4-fluorophenyl)-1H-pyrazolo[3,4-c]pyridine-4-carboxylic acid (6-bromopyridin-3-ylmethyl)-amide (80 mg, 0.2 mmol) in DMSO (3 mL) was added magnesium bromide ethanesulfinate salt (122 mg, 0.618 mmol) (prepared by treating the Grignard reagent, ethylmagnesium bromide with SO2) followed by copper iodide (210 mg, 1.1 mmol). The mixture was warmed in a microwave at 130° C. for 1 hour. The reaction was monitored by TLC (EtOAc) indicating a major new more polar product than starting bromide. The reaction was diluted with first saturated aqueous potassium carbonate (5 mL) and then saturated aqueous ammonium chloride (10 mL) and extracted with EtOAc (5×10 mL). The combined organic layers were washed with saturated aqueous ammonium chloride (3×10 mL), brine (3×10 mL), dried over magnesium sulfate, treated with activated carbon, filtered through diatomaceous earth and concentrated. The solid was dissolved in dichloromethane and purified by silica gel chromatography eluting with EtOAc-dichloromethane (25:75, then 1:1, then 66:34, then 75:25). The material from the column was triturated with ether to afford the title compound as a white solid.

1. customprepared
2. extractionsaturated aqueous ammonium chloride (10 mL) and extracted with EtOAc (5×10 mL)
3. washThe combined organic layers were washed with saturated aqueous ammonium chloride (3×10 mL), brine (3×10 mL)
4. dry with materialdried over magnesium sulfate
5. additiontreated with activated carbon
6. filtrationfiltered through diatomaceous earth
7. concentrationconcentrated
8. dissolutionThe solid was dissolved in dichloromethane
9. custompurified by silica gel chromatography
10. washeluting with EtOAc-dichloromethane (25:75
11. customThe material from the column was triturated with ether

ORD record

ord-f63636a851ad4c0fa5e02a18a8692f30

Source dataset

uspto-grants-2012_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08338610B2