3-Bromo-2-methyl-5-nitropyridine → 4-Bromo-5-methyl-1H-pyrrolo[2,3-c]pyridine

To a stirred suspension of vinylmagnesium bromide (1 M in THF, 37.5 mL, 37.50 mmol) was added dropwise a solution of 3-bromo-2-methyl-5-nitropyridine (2.50 g, 11.52 mmol) in THF, under an atmosphere of nitrogen, at 0° C. The resulting solution was allowed to warm to RT and stirred for 1 day then quenched with saturated NH4Cl(aq). The resulting mixture was partitioned between EtOAc and water, the organic layer separated, dried (MgSO4) and evaporated to give a red crude oil, which was purified by column chromatography (Si—PCC, 50-100% EtOAc in cyclohexane) followed by reverse phase HPLC (Phenomenex Gemini 5u C18, 0.1% formic acid in water on a gradient of methanol 5-75%). The relevant HPLC fractions were loaded onto an Isolute® SCX-2 cartridge, the cartridge was washed with MeOH and the desired product eluted with 2 M NH3 in MeOH to give the title compound as a pale yellow solid (22 mg, 1%). LCMS (Method H): RT 2.23 min, [M+H]+ 211.1 (79Br), 213.1 (81Br)

1. customat 0° C
2. customthen quenched with saturated NH4Cl(aq)
3. customThe resulting mixture was partitioned between EtOAc and water
4. customthe organic layer separated
5. dry with materialdried (MgSO4)
6. customevaporated
7. customto give a red crude oil, which
8. customwas purified by column chromatography (Si—PCC, 50-100% EtOAc in cyclohexane)
9. washthe cartridge was washed with MeOH
10. washthe desired product eluted with 2 M NH3 in MeOH

ORD record

ord-6da0938b1dad4f62ab328cf95b8ef3e4

Source dataset

uspto-grants-2013_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08394796B2