Methyl iodide → 8-Isobutyryloxy-5-methyl-6-oxo-5,6-dihydro-pyrido[2,3-b]pyrazine-7-carboxylic acid methyl ester

HRID 241780Notes

Reaction equation

[CH3:1][O:2][C:3]([C:5]1[C:14](=[O:15])[NH:13][C:8]2=[N:9][CH:10]=[CH:11][N:12]=[C:7]2[C:6]=1[O:16][C:17](=[O:21])[CH:18]([CH3:20])[CH3:19])=[O:4].[C:22](=O)([O-])[O-].[K+].[K+].CI>C(#N)C.C(OCC)(=O)C.O>[CH3:1][O:2][C:3]([C:5]1[C:14](=[O:15])[N:13]([CH3:22])[C:8]2=[N:9][CH:10]=[CH:11][N:12]=[C:7]2[C:6]=1[O:16][C:17](=[O:21])[CH:18]([CH3:19])[CH3:20])=[O:4]

Participants

Conditions

Temperature: 100 °C

Procedure

To a suspension of 8-isobutyryloxy-6-oxo-5,6-dihydro-pyrido[2,3-b]pyrazine-7-carboxylic acid methyl ester (0.422 g) (Example 7.2) in acetonitrile (12 ml) was added potassium carbonate (0.401 g) followed by methyl iodide (0.30 ml). The reaction mixture was heated to 100° C. for 10 minutes in a microwave, and then cooled to ambient temperature. The reaction mixture was diluted with ethyl acetate and water. The phases were separated. The organic phase was washed with water and brine, dried over magnesium sulfate and concentrated. The residue was purified by column chromatography on silica gel (eluent: ethyl acetate/hexane 1:2 to 1:1) to give 8-isobutyryloxy-5-methyl-6-oxo-5,6-dihydro-pyrido[2,3-b]pyrazine-7-carboxylic acid methyl ester as an orange oil (0.418 g). 1H-NMR (400 MHz, CDCl3): 1.36 (d, 6H), 2.95 (sept, 1H), 3.79 (s, 3H), 3.94 (s, 3H), 8.49 (d, 1H), 8.59 (d, 1H) ppm.

Workup

temperaturecooled to ambient temperature
customThe phases were separated
washThe organic phase was washed with water and brine
dry with materialdried over magnesium sulfate
concentrationconcentrated
customThe residue was purified by column chromatography on silica gel (eluent: ethyl acetate/hexane 1:2 to 1:1)

Sources & evidence

ORD record: ord-e7a01f9fd2d142cbb94f96813a02a712
Source dataset: uspto-grants-2014_02
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08653078B2

Reaction notes

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