3-Methyl-2-butanone → HCID 66743775, compound

HRID 2363946Notes

Reaction equation

[NH2:1][C:2]1[CH:6]=[C:5]([C:7]2[CH:12]=[CH:11][N:10]=[CH:9][CH:8]=2)[S:4][C:3]=1[C:13]([NH2:15])=[O:14].[CH3:16][CH:17]([CH3:21])[C:18](=O)[CH3:19].O.C1(C)C=CC(S(O)(=O)=O)=CC=1.C(=O)([O-])O.[Na+]>CN(C=O)C.ClCCl.C(O)(=O)C>[CH:17]([C:18]1([CH3:19])[NH:1][C:2]2[CH:6]=[C:5]([C:7]3[CH:8]=[CH:9][N:10]=[CH:11][CH:12]=3)[S:4][C:3]=2[C:13](=[O:14])[NH:15]1)([CH3:21])[CH3:16]

Participants

Conditions

Temperature: 70 °C

Procedure

A mixture of 3-amino-5-(pyridin-4-yl)thiophene-2-carboxamide (0.108 g, 0.500 mmol), 3-methyl-2-butanone (3.0 mL), p-toluenesulfonic acid monohydrate (0.0095 g, 0.050 mmol) and acetic acid (3.0 mL) was stirred overnight at 70° C. in a sealed tube. The mixture was poured into sat. aqueous sodium hydrogen carbonate (150 mL). Extraction with ethyl acetate-tetrahydrofuran (3:1, 2×100 mL), drying over magnesium sulfate, filtration and concentration at reduced pressure gave a solid. This solid was dissolved with DMF-dichloromethane (2:5, 7 mL) and purified by column chromatography (Combiflash, 12 g silica gel, ethyl acetate to 90:10 ethyl acetate/methanol), then recrystallized from methanol-ethyl acetate to afford the title compound (0.0125 g, 8.7%) as a yellow solid:

Workup

extractionExtraction with ethyl acetate-tetrahydrofuran (3:1, 2×100 mL)
dry with materialdrying over magnesium sulfate, filtration and concentration at reduced pressure
customgave a solid
custompurified by column chromatography (Combiflash, 12 g silica gel, ethyl acetate to 90:10 ethyl acetate/methanol)
customrecrystallized from methanol-ethyl acetate

Sources & evidence

ORD record: ord-8e8f72b40a2a49eeb65e33ba9bd6f36d
Source dataset: uspto-grants-2014_04
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08691828B2

Reaction notes

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