Dimethylformamide → ethyl (4S)-6-cyano-2-ethyl-8-methoxy-4-methyl-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-carboxylate

Temperatur

140 °C

To a mixture of ethyl (4S)-6-bromo-2-ethyl-8-methoxy-4-methyl-1-oxo-1,2,3,4-tetrahydropyrrolo[1,2-a]pyrazin-7-carboxylate (4.1 g, 11.41 mmol; Example 62, step 7), zinc dust (0.15 g, 2.28 mmol), zinc cyanide (1.11 g, 9.47 mmol), triphenylphosphine (0.46 g, 1.77 mmol), and tris(dibenzylideneacetone)dipalladium (0) (1.57 g, 1.71 mmol) in anhydrous DMF (10 mL) was purged with argon gas for 15 minutes. The mixture was heated in a sealed tube in an oil bath at 140° C. overnight. The reaction mixture was filtered through a pad of Celite, and the filtrate concentrated under vacuum. The residue was partitioned between chloroform and aqueous EDTA monosodium salt. The mixture was stirred at room temperature for 30 minutes. The organic extract was washed with brine, dried over anhydrous magnesium sulfate, filtered, and concentrated under vacuum. The residue was subjected to column chromatography on silica gel eluted with 0 to 40% ethyl acetate in chloroform gradient. Collection and concentration of appropriate fractions provided the title nitrile.

1. customwas purged with argon gas for 15 minutes
2. filtrationThe reaction mixture was filtered through a pad of Celite
3. concentrationthe filtrate concentrated under vacuum
4. customThe residue was partitioned between chloroform and aqueous EDTA monosodium salt
5. extractionThe organic extract
6. washwas washed with brine
7. dry with materialdried over anhydrous magnesium sulfate
8. filtrationfiltered
9. concentrationconcentrated under vacuum
10. washeluted with 0 to 40% ethyl acetate in chloroform gradient
11. customCollection and concentration of appropriate fractions

ORD-Eintrag

ord-18708559f83344628014bb586263e8d6

Quelldatensatz

uspto-grants-2009_05

DOI

10.6084/m9.figshare.5104873.v1

Patentnummer

US07538112B2