Dimethylformamide → Methyl 2-methylpyrimidine-5-carboxylate
Reaction equation
Cl.[C:2]([NH2:5])(=O)[CH3:3].[CH3:6][O:7][CH:8]([O:16]C)[C:9]([C:12](OC)=O)=[CH:10][O-].[Na+].C[N:20](C)C=O>>[CH3:3][C:2]1[N:5]=[CH:12][C:9]([C:8]([O:7][CH3:6])=[O:16])=[CH:10][N:20]=1Participants
Conditions
- Temperature
- 100 °C
Procedure
N-(4-chlorophenyl)-N-{(2S,4R)-2-methyl-1-[(2-methylpyrimidin-5-yl)carbonyl]-1,2,3,4-tetrahydroquinolin-4-yl}acetamide was prepared following general procedure H, substituting 2-methylpyrimidine-5-carbonyl chloride for 6-trifluoromethyl nicotinyl chloride. (2-methylpyrimidine-5-carbonyl chloride was prepared in four steps. To a solution of 3,3-dimethoxypropionate in ethylene glycol dimethyl ether was added sodium hydride at 0° C., then methyl formate. The reaction mixture was warmed up to 50° C. for 30 m. and then stirred at room temperature for 20 h. Anhydrous diethyl ether was added and the precipitate was filtered to give sodium 2-(dimethoxymethyl)-3-methoxy-3-oxoprop-1-en-1-olate. To a solution of acetamide hydrochloride in dimethylformamide was added preformed sodium 2-(dimethoxymethyl)-3-methoxy-3-oxoprop-1-en-1-olate. Reaction mixture was heated to 100° C. for 1 h. to give methyl 2-methylpyrimidine-5-carboxylate. Hydrolysis of the ester with sodium hydroxide gave 2-methylpyrimidine-5-carboxylic acid. Subsequent treatment of this carboxylic acid with oxalyl chloride and catalytic DMF afforded 2-methylpyrimidine-5-carbonyl chloride in decent yield). The rest of the procedures were followed as indicated in general procedure H to afford N-(4-chlorophenyl)-N-{(2S,4R)-2-methyl-1-[(2-methylpyrimidin-5-yl)carbonyl]-1,2,3,4-tetrahydroquinolin-4-yl}acetamide.
Workup
- customReaction mixture
Sources & evidence
- ORD record
- ord-48311e6822004b5fb134fa57b17d727d
- Source dataset
- uspto-grants-2009_03
- Patent number
- US07504508B2
Reaction notes
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