Citric Acid → HCID 86630919, compound

HRID 220115Notes

Reaction equation

HRID 220115 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:27]3[CH2:26][C:25](=[N:28][OH:29])[CH:24]=[CH:23][C:22]=3[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1.Br[CH2:31][CH2:32][CH2:33][CH2:34][N:35]([CH2:42][CH2:43][S:44]([CH3:47])(=[O:46])=[O:45])[C:36](=[O:41])[C:37]([F:40])([F:39])[F:38].C(=O)([O-])[O-].[K+].[K+].C(O)(=O)CC(CC(O)=O)(C(O)=O)O>CN(C)C(=O)C>[Cl:1][C:2]1[CH:3]=[C:4]([NH:17][C:18]2[C:27]3[CH2:26][C:25](=[N:28][O:29][CH2:31][CH2:32][CH2:33][CH2:34][N:35]([CH2:42][CH2:43][S:44]([CH3:47])(=[O:45])=[O:46])[C:36](=[O:41])[C:37]([F:39])([F:38])[F:40])[CH:24]=[CH:23][C:22]=3[N:21]=[CH:20][N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH2:9][C:10]1[CH:15]=[CH:14][CH:13]=[C:12]([F:16])[CH:11]=1

Participants

6

Reactant 4

HCID 311Citric AcidHCID 11430Potassium CarbonateHCID 54156798HCID 54156798, compoundHCID 136346313HCID 136346313, compound

Product 1

HCID 86630919HCID 86630919, compoundYield 29.9%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Conditions

Temperature
60 °C

Procedure

In N,N-dimethylacetamide (1.5 ml) were dissolved 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(hydroxyimino)quinazoline (V-2, 84 mg) and N-(4-bromobutyl)-N-(2-methanesulfonylethyl)-2,2,2-trifluoroacetamide (71 mg), and potassium carbonate (41 mg) was added, followed by stirring at 60° C. for 1.3 hours with heating. Thereafter, the reaction mixture was poured into 0.5 M citric acid, followed by extraction with ethyl acetate. The organic layer was washed with water and aqueous sodium chloride solution, and dried over magnesium sulfate. The crude product was purified by silica gel chromatography (eluting with hexane:ethyl acetate=1:4) to obtain 4-(3-chloro-4-(3-fluorobenzyloxy)phenylamino)-6-(4-(N-(2-(methanesulfonyl)ethyl)-2,2,2-trifluoroacetamido)butyloxyimino)quinazoline (V-14, 41 mg) as a pale yellow solid.

Workup

  1. additionwas added
  2. temperaturewith heating
  3. extractionfollowed by extraction with ethyl acetate
  4. washThe organic layer was washed with water and aqueous sodium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. customThe crude product was purified by silica gel chromatography (eluting with hexane:ethyl acetate=1:4)

Sources & evidence

ORD record
ord-c26cf34056484fd585359878d39b09f9
Source dataset
uspto-grants-2012_06
Patent number
US08202879B2

Reaction notes

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