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

HRID 2197509Notes

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-dbf166af49034067825dd7c4307d5612
Source dataset: uspto-grants-2012_12
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08338598B2

Reaction notes

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