7-Benzyloxy-4-(4-chloro-2,6-difluoroanilino)-6-methoxyquinazoline → 4-(4-Chloro-2,6-difluoroanilino)-7-hydroxy-6-methoxyquinazoline

HRID 577387Notes

Reaction equation

HRID 577387 reaction equation
C([O:8][C:9]1[CH:18]=[C:17]2[C:12]([C:13]([NH:19][C:20]3[C:25]([F:26])=[CH:24][C:23]([Cl:27])=[CH:22][C:21]=3[F:28])=[N:14][CH:15]=[N:16]2)=[CH:11][C:10]=1[O:29][CH3:30])C1C=CC=CC=1>C(O)(C(F)(F)F)=O>[Cl:27][C:23]1[CH:22]=[C:21]([F:28])[C:20]([NH:19][C:13]2[C:12]3[C:17](=[CH:18][C:9]([OH:8])=[C:10]([O:29][CH3:30])[CH:11]=3)[N:16]=[CH:15][N:14]=2)=[C:25]([F:26])[CH:24]=1

Participants

3

Reactant 1

HCID 110590287-Benzyloxy-4-(4-chloro-2,6-difluoroanilino)-6-methoxyquinazoline

Product 1

HCID 1354968544-(4-Chloro-2,6-difluoroanilino)-7-hydroxy-6-methoxyquinazolineYield 80%

Reagents, catalysts & solvents 1

HCID 6422Trifluoroacetic acidSolvent

Procedure

A solution of 7-benzyloxy-4-(4-chloro-2,6-difluoroanilino)-6-methoxyquinazoline (200 mg, 0.47 mmol) in TFA (3 ml) was stirred at 80° C. for 3 hours. After cooling, the volatiles were removed under vacuum and the residue was dissolved in water containing 5% methanol. The pH was adjusted to 8 with sodium hydrogen carbonate and the solid was collected by filtration and washed with water. The solid was solubilised in a mixture of ethyl acetate/methanol/methylene chloride (47/6/47). The volatiles were removed under vacuum to give 4-(4-chloro-2,6-difluoroanilino)-7-hydroxy-6-methoxyquinazoline (126 mg, 80%).

Workup

  1. temperatureAfter cooling
  2. customthe volatiles were removed under vacuum
  3. dissolutionthe residue was dissolved in water containing 5% methanol
  4. filtrationthe solid was collected by filtration
  5. washwashed with water
  6. additionThe solid was solubilised in a mixture of ethyl acetate/methanol/methylene chloride (47/6/47)
  7. customThe volatiles were removed under vacuum

Sources & evidence

ORD record
ord-2edf2dfc24e0486e9d6baa983d2e2844
Source dataset
uspto-grants-2015_05
Patent number
US09040548B2

Reaction notes

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