Citric Acid → HCID 86630919, compound

HRID 1801865Notes

Reaction equation

HRID 1801865 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 13 hours with heating. Thereafter, the reaction mixture was poured into 0.5M 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-a3a6417902444e86897ea70e5ad95844
Source dataset
uspto-grants-2013_01
Patent number
US08349857B2

Reaction notes

Loading…