Bromomethylcyclopropane → 5-Bromo-1-(cyclopropylmethyl)-3-methylpyridin-2-one

HRID 518451Notes

Reaction equation

[Br:1][C:2]1[CH:3]=[C:4]([CH3:9])[C:5](=[O:8])[NH:6][CH:7]=1.Br[CH2:11][CH:12]1[CH2:14][CH2:13]1>>[Br:1][C:2]1[CH:3]=[C:4]([CH3:9])[C:5](=[O:8])[N:6]([CH2:11][CH:12]2[CH2:14][CH2:13]2)[CH:7]=1

Participants

Reactant 2

HCID 81503Bromomethylcyclopropane

HCID 2854365-Bromo-2-hydroxy-3-methylpyridine

Product 1

HCID 814220925-Bromo-1-(cyclopropylmethyl)-3-methylpyridin-2-one

Procedure

5-bromo-3-methyl-1H-pyridin-2-one was N-alkylated with bromomethylcyclopropane to give 5-bromo-1-(cyclopropylmethyl)-3-methylpyridin-2-one. 5-bromo-1-(cyclopropylmethyl)-3-methylpyridin-2-one (100 mg, 0.41 mmol), [2-(2,4-difluorophenoxy)-5-(ethylsulfonylamino)phenyl]boronic acid (217 mg, 0.5 mol), K3PO4 (263 mg, 1.24 mmol) and Pd(dppf)Cl2 (30 mg, 41.3 umol) in dioxane (8 mL)/water (1 mL) were purged with N2 and heated at 70-80° C. for 12 h. Preparative HPLC gave the title compound (56.0 mg, 28.6% yield) as dull-red semisolid. 1H NMR (CDCl3, 400 MHz): δ 7.74 (s, 1H), 7.61 (s, 1H), 7.28 (d, J=2.0 Hz, 1H), 7.10-7.15 (m, 1H), 6.92-7.00 (m, 2H), 6.82-6.89 (m, 1H), 6.80 (d, J=8.8 Hz, 1H), 6.71 (br. s., 1H), 3.93 (d, J=7.2 Hz, 3H), 3.12-3.21 (m, 2H), 2.24 (s, 3H), 1.42 (t, J=7.2 Hz, 3H), 1.22-1.33 (m, 1H), 0.57-0.67 (m, 2H), 0.36-0.43 (m, 2H). LCMS: 475.1 (M+1)+

Sources & evidence

ORD record: ord-bc43ab0e3b484ab48f80af551ddf4af5
Source dataset: uspto-grants-2015_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09115114B2

Reaction notes

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