Citric Acid → HCID 69205223, compound

HRID 2182645Notes

Reaction equation

HRID 2182645 reaction equation
[F:1][C:2]1[CH:3]=[CH:4][C:5]([O:17][CH3:18])=[C:6]([C:8]([CH3:16])([CH3:15])[CH2:9][C:10](=[O:14])[C:11]([OH:13])=O)[CH:7]=1.S(Cl)(Cl)=O.N[C:24]1[CH:33]=[CH:32][CH:31]=[C:30]2[C:25]=1[CH:26]=[CH:27][CH:28]=[N:29]2.C(O)(=O)CC(CC(O)=O)(C(O)=O)O.C[N:48](C=O)C>>[N:29]1[C:30]2[C:25](=[CH:24][CH:33]=[CH:32][CH:31]=2)[C:26]([NH:48][C:11](=[O:13])[C:10](=[O:14])[CH2:9][C:8]([C:6]2[CH:7]=[C:2]([F:1])[CH:3]=[CH:4][C:5]=2[O:17][CH3:18])([CH3:16])[CH3:15])=[CH:27][CH:28]=1

Participants

6

Reactant 5

HCID 311Citric AcidHCID 6228DimethylformamideHCID 119115-AminoquinolineHCID 24386Thionyl ChlorideHCID 15965859HCID 15965859, compound

Product 1

HCID 69205223HCID 69205223, compound

Procedure

540 mg (2.13 mmol) of 4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-oxopentanoic acid (WO 00/32584) in 15 ml of DMF is mixed at −5° C. under argon with 0.18 ml of thionyl chloride. After 20 minutes of stirring at −3° C. to +3° C., 470 mg (3.26 mmol) of 5-aminoquinoline is added. It is allowed to heat to room temperature, stirred for another 16 hours, mixed with 10% citric acid, extracted with ethyl acetate, the organic phase is washed with water and dried (Na2SO4). After chromatography on silica gel with hexane-ethyl acetate (0-75%), 680 mg of N-(quinolin-4-yl)-4-(5-fluoro-2-methoxyphenyl)-4-methyl-2-oxopentanoic acid amide is obtained, which is dissolved in 22 ml of DMF and cooled to 0° C. The solution is mixed with 1.80 ml of (trifluoromethyl)trimethylsilane and 2.43 g of cesium carbonate and stirred for 16 hours at room temperature. Water is added, extracted with ethyl acetate, the organic phase is washed with water and dried on sodium sulfate. The intermediate product that is concentrated by evaporation is taken up in 10 ml of THF, and 5.5 ml of a 1 M solution of tetrabutylammonium fluoride is added. It is stirred for 1.5 hours, water is added, extracted with ethyl acetate, the organic phase is washed with water and dried on sodium sulfate. After chromatography on silica gel with hexane-ethyl acetate (0-70%), 420 mg of product is obtained.

Workup

  1. stirringstirred for another 16 hours
  2. extractionextracted with ethyl acetate
  3. washthe organic phase is washed with water
  4. dry with materialdried (Na2SO4)

Sources & evidence

ORD record
ord-966ae75138df4b4d8c03aeea83d46825
Source dataset
uspto-grants-2005_05
Patent number
US06897224B2

Reaction notes

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