Formic Acid → 2-(Ethoxymethyl-amino)-N-(5-phenoxy-thiophen-2-ylmethyl)-nicotinamide
Reaction equation
[NH2:1][C:2]1[N:23]=[CH:22][CH:21]=[CH:20][C:3]=1[C:4]([NH:6][CH2:7][C:8]1[S:9][C:10]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:11][CH:12]=1)=[O:5].C[C:25]1(C)NC(=O)N[C:26]1=[O:31].[CH:33](O)=O.O>C(O)C>[CH2:26]([O:31][CH2:33][NH:1][C:2]1[N:23]=[CH:22][CH:21]=[CH:20][C:3]=1[C:4]([NH:6][CH2:7][C:8]1[S:9][C:10]([O:13][C:14]2[CH:19]=[CH:18][CH:17]=[CH:16][CH:15]=2)=[CH:11][CH:12]=1)=[O:5])[CH3:25]Participants
6
Procedure
To a solution of the resulting 2-amino-N-(5-phenoxy-thiophen-2-ylmethyl)-nicotinamide (602 mg, 1.85 mmol) in ethanol (40 mL) were added 5,5-dimethylhydantoin (260 mg, 2.04 mmol), 37% formic acid aqueous solution (3.00 mL, 23.6 mmol), and the solution was stirred under reflux for 1 hour. Water was added to the reaction mixture, which was then extracted with ethyl acetate, the organic layer was sequentially washed with water and brine, dried over anhydrous sodium sulfate, and then, evaporated in vacuo. The resulting residue was purified by silica gel chromatography (hexane-ethyl acetate), and the title compound (430 mg, 1.12 mmol, 61%) was obtained.
Workup
- temperatureunder reflux for 1 hour
- extractionwas then extracted with ethyl acetate
- washthe organic layer was sequentially washed with water and brine
- dry with materialdried over anhydrous sodium sulfate
- customevaporated in vacuo
- customThe resulting residue was purified by silica gel chromatography (hexane-ethyl acetate)
Sources & evidence
- ORD record
- ord-5d4012a473484992aac5159b5c6f5aed
- Source dataset
- uspto-grants-2011_04
- Patent number
- US07932272B2
Reaction notes
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