N-bromobutanimide → 3-bromo-5'-chloro-2'-fluoro-N-((tetrahydro-2H-pyran-4-yl)methyl)-2,4'-bipyridin-6-amine

HRID 1963826Notes

Reaction equation

[Cl:1][C:2]1[C:3]([C:9]2[CH:14]=[CH:13][CH:12]=[C:11]([NH:15][CH2:16][CH:17]3[CH2:22][CH2:21][O:20][CH2:19][CH2:18]3)[N:10]=2)=[CH:4][C:5]([F:8])=[N:6][CH:7]=1.[Br:23]N1C(=O)CCC1=O>C(#N)C>[Br:23][C:14]1[C:9]([C:3]2[C:2]([Cl:1])=[CH:7][N:6]=[C:5]([F:8])[CH:4]=2)=[N:10][C:11]([NH:15][CH2:16][CH:17]2[CH2:22][CH2:21][O:20][CH2:19][CH2:18]2)=[CH:12][CH:13]=1

Participants

Conditions

Temperature: 90 °C

Procedure

A mixture of 5′-chloro-2′-fluoro-N-((tetrahydro-2H-pyran-4-yl)methyl)-2,4′-bipyridin-6-amine (516 mg, 1.60 mmol) and N-bromosuccinimide (286 mg, 1.60 mmol) in acetonitrile (12 mL) was stirred at 90° C. for 3 hr in a sealed vessel. Volatiles were removed under reduced pressure. The resulting residue was dissolved in ethyl acetate and washed sequentially with saturated aqueous sodium bicarbonate and brine. The organic phase was dried (Na2SO4), filtered, and concentrated. The crude material was purified by column chromatography over silica gel (heptanes/ethyl acetate gradient) to yield 608 mg of the desired product. LCMS (m/z): 402.0 [M+H]+; Retention time=1.03 min.

Workup

customVolatiles were removed under reduced pressure
dissolutionThe resulting residue was dissolved in ethyl acetate
washwashed sequentially with saturated aqueous sodium bicarbonate and brine
dry with materialThe organic phase was dried (Na2SO4)
filtrationfiltered
concentrationconcentrated
customThe crude material was purified by column chromatography over silica gel (heptanes/ethyl acetate gradient)

Sources & evidence

ORD record: ord-1f7ba8654496413ea0207c460e2688fc
Source dataset: uspto-grants-2013_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08415381B2

Reaction notes

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