Hexamethylphosphoramide → 4-Amino-3-(4-methylisoxazole-5-ylcarbonylamino)quinoline

HRID 580519Notes

Reaction equation

HRID 580519 reaction equation
[CH3:1][C:2]1N=C[O:5][C:6]=1[C:7]([OH:9])=O.S(Cl)(Cl)=O.[NH2:14][C:15]1[CH:16]=[N:17][C:18]2[C:23]([C:24]=1[NH2:25])=[CH:22][CH:21]=[CH:20][CH:19]=2.[CH3:26][N:27](C)P(N(C)C)(N(C)C)=O>C(#N)C.C(=O)(O)[O-].[Na+]>[NH2:25][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:6]1[O:5][N:27]=[CH:26][C:2]=1[CH3:1])=[O:9]

Participants

7

Reactant 4

HCID 12679HexamethylphosphoramideHCID 24386Thionyl ChlorideHCID 2923114-Methyl-1,3-oxazole-5-carboxylic acidHCID 15142893,4-Diaminoquinoline

Product 1

HCID 201341164-Amino-3-(4-methylisoxazole-5-ylcarbonylamino)quinoline

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 516892Sodium BicarbonateSolvent

Procedure

To a solution of 300 mg of 4-methyloxazole-5-carboxylic acid in 4 ml of hexamethylphosphoramide and 0.4 ml of acetonitrile is added 268 mg of thionyl chloride at -5°-0° C. under nitrogen. After stirring at the same temperature for 30 minutes, 340 mg of 3,4-diaminoquinoline A1 is added and stirred at 0°-5° C. for 3 hours. The mixture is diluted with ice-water and neutralized with saturated aqueous sodium bicarbonate. The resulting solid is filtered and washed with water to give 425 mg of 4-amino-3-(4-methylisoxazole-5-ylcarbonylamino)quinoline as crude crystals. It is suspended in 12 ml of Dowtherm A (Dow Chemimical Co.) and refluxed for 2.5 hours. The cooled mixture is diluted with 50 ml of n-hexane and the resulting solid is collected by filtration. It is chromatographed on silica gel with dichloromethane-methanol (20:1 v/v) as eluent to yield a crude solid which is recrystallized from ethyl acetate-methanol, giving 297 mg of C99 as pale yellow crystals.

Workup

  1. stirringstirred at 0°-5° C. for 3 hours
  2. filtrationThe resulting solid is filtered
  3. washwashed with water

Sources & evidence

ORD record
ord-50d0b5596cc24c4487e3a777096879c7
Source dataset
uspto-grants-1988_06
Patent number
US04753951

Reaction notes

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