Sodium Bicarbonate → 1-(2-bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethyl-pent-4-en-1-one

HRID 1677513

Reaction equation

[Cl-].C([Al+]CC)C.[Br:7][C:8]1[N:9]=[C:10]2[CH:16]=[CH:15][NH:14][C:11]2=[N:12][CH:13]=1.[CH3:17][C:18]([CH3:25])([CH2:22][CH:23]=[CH2:24])[C:19](Cl)=[O:20].C([O-])(O)=O.[Na+]>ClCCl>[Br:7][C:8]1[N:9]=[C:10]2[C:16]([C:19](=[O:20])[C:18]([CH3:25])([CH3:17])[CH2:22][CH:23]=[CH2:24])=[CH:15][NH:14][C:11]2=[N:12][CH:13]=1

Participants

Conditions

Temperature: 2.5 °C

Procedure

Diethylaluminum chloride (1.0 M in CH2Cl2, 23.4 mL, 23.4 mmol) was added to a 0-5° C. mixture of 2-bromo-5H-pyrrolo[2,3-b]pyrazine (1.55 g, 7.80 mmol) and 30 mL of dichloromethane in a sealed tube, and the mixture was stirred at 0-5° C. for 20 min. The solution of crude 2,2-dimethyl-4-pentenoyl chloride prepared in the previous step was added dropwise. The resulting mixture was stirred at 60° C. for 64 h, then cooled to 0-5° C. A sat. aq. NaHCO3 solution (50 mL) was carefully added, and the mixture was extracted with three 100 mL portions of ethyl acetate. The combined organic layers were dried over MgSO4, filtered and concentrated to a residue. Column chromatography (0→50% EtOAc/hexanes) afforded 1.033 g (43%) of impure 1-(2-bromo-5H-pyrrolo[2,3-b]pyrazin-7-yl)-2,2-dimethyl-pent-4-en-1-one as a brown solid, which was used without further purification. The major impurity is s.m. (typically 15-30% of the mixture).

Workup

additionwas added dropwise
stirringThe resulting mixture was stirred at 60° C. for 64 h
temperaturecooled to 0-5° C
extractionthe mixture was extracted with three 100 mL portions of ethyl acetate
dry with materialThe combined organic layers were dried over MgSO4
filtrationfiltered
concentrationconcentrated to a residue

Sources & evidence

ORD record: ord-223468fec13a435980aeff76d065aeb0
Source dataset: uspto-grants-2011_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08008298B2

Linked notes

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