Trifluoroacetic acid → N-(4-bromo-2,6-difluorophenyl)-6-methoxy-7-(piperidin-4-ylmethoxy)quinazolin-4-amine

HRID 577383Notes

Reaction equation

HRID 577383 reaction equation
[Br:1][C:2]1[CH:35]=[C:34]([F:36])[C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:20][CH:21]4[CH2:26][CH2:25][N:24](C(OC(C)(C)C)=O)[CH2:23][CH2:22]4)=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:37])[CH:3]=1.C(O)(C(F)(F)F)=O>C(Cl)Cl>[Br:1][C:2]1[CH:35]=[C:34]([F:36])[C:5]([NH:6][C:7]2[C:16]3[C:11](=[CH:12][C:13]([O:19][CH2:20][CH:21]4[CH2:26][CH2:25][NH:24][CH2:23][CH2:22]4)=[C:14]([O:17][CH3:18])[CH:15]=3)[N:10]=[CH:9][N:8]=2)=[C:4]([F:37])[CH:3]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 109738974-(4-Bromo-2,6-difluoroanilino)-7-(1-(tert-butoxycarbonyl)piperidin-4-ylmethoxy)-6-methoxyquinazoline

Product 1

HCID 5329051N-(4-bromo-2,6-difluorophenyl)-6-methoxy-7-(piperidin-4-ylmethoxy)quinazolin-4-amineYield 23%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A solution of 4-(4-bromo-2,6-difluoroanilino)-7-(1-(tert-butoxycarbonyl)piperidin-4-ylmethoxy)-6-methoxyquinazoline (578 mg, 1 mmol) in methylene chloride (10 ml) containing TFA (4 ml) was stirred at ambient temperature for 2 hours. The volatiles were removed under vacuum and the residue was suspended in water. The aqueous layer was adjusted to approximately pH10 and was extracted with methylene chloride. The organic layer was washed with water, brine, dried (MgSO4) and the volatiles were removed by evaporation. The residue was triturated with ether and dried under vacuum to give 4-(4-bromo-2,6-difluoroanilino)-6-methoxy-7-(piperidin-4-ylmethoxy)quinazoline (110 mg, 23%).

Workup

  1. customThe volatiles were removed under vacuum
  2. extractionwas extracted with methylene chloride
  3. washThe organic layer was washed with water, brine
  4. dry with materialdried (MgSO4)
  5. customthe volatiles were removed by evaporation
  6. customThe residue was triturated with ether
  7. customdried under vacuum

Sources & evidence

ORD record
ord-78e723042a034d9bb0ce0a0bf0a912e7
Source dataset
uspto-grants-2015_05
Patent number
US09040548B2

Reaction notes

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