1-Methylcyclohexanecarbonyl chloride → (2-bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)-(1-methyl-cyclohexyl)-methanone

Temperature

0 °C

A suspension of 2-bromo-5H-pyrrolo[2,3-b]pyrazine (104 mg, 0.53 mmol) in anhydrous dichloromethane (3 ml) was cooled to 0° C. under N2. Diethyl aluminum chloride (1M in hexanes, 1.57 ml, 1.57 mmol) was added quickly, and the reaction mixture was stirred for 30 minutes. 1-Methyl-cyclohexanecarbonyl chloride (844 mg, 5.3 mmol) was added dropwise, and the reaction mixture was refluxed overnight. The reaction mixture was cooled to 0° C. and quenched with saturated aqueous NaHCO3. The biphasic solution was concentrated, and the remaining aqueous solution was extracted with ethyl acetate (3×). The organic layers were collected, dried over MgSO4, filtered, and concentrated giving a greenish oil. The residue was purified by silica gel chromatography using 20-50% EtOAc in hexanes as eluant to provide 144 mg (85%) of (2-bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)-(1-methyl-cyclohexyl)-methanone as a light yellow solid. MP 198-199° C., M+H=322.

1. temperaturethe reaction mixture was refluxed overnight
2. temperatureThe reaction mixture was cooled to 0° C.
3. customquenched with saturated aqueous NaHCO3
4. concentrationThe biphasic solution was concentrated
5. extractionthe remaining aqueous solution was extracted with ethyl acetate (3×)
6. customThe organic layers were collected
7. dry with materialdried over MgSO4
8. filtrationfiltered
9. concentrationconcentrated
10. customgiving a greenish oil
11. customThe residue was purified by silica gel chromatography

ORD record

ord-dace3c7de7bd4833a5274f7815976501

Source dataset

uspto-grants-2012_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08119636B2