Thionyl Chloride → 4-Methylamino-3-[(3-methylisoxazole-5-ylcarbonyl)amino]quinoline
Reaction equation
[CH3:1][C:2]1[CH:6]=[C:5]([C:7]([OH:9])=O)[O:4][N:3]=1.S(Cl)(Cl)=O.[NH2:14][C:15]1[CH:16]=[N:17][C:18]2[C:23]([C:24]=1[NH:25][CH3:26])=[CH:22][CH:21]=[CH:20][CH:19]=2>CN(C)P(N(C)C)(N(C)C)=O.C(#N)C.C(=O)(O)[O-].[Na+]>[CH3:26][NH:25][C:24]1[C:23]2[C:18](=[CH:19][CH:20]=[CH:21][CH:22]=2)[N:17]=[CH:16][C:15]=1[NH:14][C:7]([C:5]1[O:4][N:3]=[C:2]([CH3:1])[CH:6]=1)=[O:9]Participants
Reactant 3
Product 1
Reagents, catalysts & solvents 3
Procedure
To a solution of 245 mg of 3-methylisoxazole-5-carboxylic acid in 20 ml of hexamethylphosphoramide and 0.4 ml of acetonitrile is added 226 mg of thionyl chloride at -5°-0° C. After stirring at the same temperature for 30 minutes, 330 mg of 3-amino-4-methylaminoquinoline A15 is added and stirred at 0°-5° C. for 5 hours. The mixture is diluted with 50 ml of ice-water and neutralized with saturated aqueous sodium bicarbonate. The resulting solid is filtered and washed with water to give 361 mg (67%) of 4-methylamino-3-[(3-methylisoxazole-5-ylcarbonyl)amino]quinoline. It is suspended in 4 ml of hexamethylphosphoramide and 1 ml of acetic acid and stirred at 180° C. (bath temperature) for 40 minutes. The cooled mixture is poured into ice-water and neutralized with aqueous sodium bicarbonate. The resulting solid is filtered, washed with water and chromatographed on silica gel with dichloromethane-methanol (25:1 v/v) as eluent. The product obtained is recrystallized from dichloromethane-methanol to give 294 mg of C102 as white crystals melting at 281°-284° C. (dec.).
Workup
- stirringstirred at 0°-5° C. for 5 hours
- filtrationThe resulting solid is filtered
- washwashed with water
Sources & evidence
- ORD record
- ord-67d306ca01054e26a41810a136d4bd2c
- Source dataset
- uspto-grants-1988_06
- Patent number
- US04753951
Reaction notes
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