Trifluoroacetic acid → N-Desmethyl vandetanib

HRID 577355

Reaction equation

HRID 577355 reaction equation
C(O)(C(F)(F)F)=O.[Br:8][C:9]1[CH:42]=[CH:41][C:12]([NH:13][C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:26][CH2:27][CH:28]4[CH2:33][CH2:32][N:31](C(OC(C)(C)C)=O)[CH2:30][CH2:29]4)=[C:21]([O:24][CH3:25])[CH:22]=3)[N:17]=[CH:16][N:15]=2)=[C:11]([F:43])[CH:10]=1>C(Cl)Cl>[Br:8][C:9]1[CH:42]=[CH:41][C:12]([NH:13][C:14]2[C:23]3[C:18](=[CH:19][C:20]([O:26][CH2:27][CH:28]4[CH2:29][CH2:30][NH:31][CH2:32][CH2:33]4)=[C:21]([O:24][CH3:25])[CH:22]=3)[N:17]=[CH:16][N:15]=2)=[C:11]([F:43])[CH:10]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 11049999tert-Butyl 4-(((4-((4-bromo-2-fluorophenyl)amino)-6-methoxyquinazolin-7-yl)oxy)methyl)piperidine-1-carboxylate

Product 1

HCID 5329048N-Desmethyl vandetanibYield 70.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

TFA (3 ml) was added to a suspension of 4-(4-bromo-2-fluoroanilino)-7-(1-(tert-butoxycarbonyl)piperidin-4-ylmethoxy)-6-methoxyquinazoline (673 mg, 1.2 mmol) in methylene chloride (10 ml). After stirring for 1 hour at ambient temperature, the volatiles were removed under vacuum. The residue was triturated with a mixture of water/ether. The organic layer was separated. The aqueous layer was washed again with ether. The aqueous layer was adjusted to pH10 with 2N aqueous sodium hydroxide. The aqueous layer was extracted with methylene chloride. The organic layer was dried (MgSO4) and the solvent was removed under vacuum. The solid was triturated with a mixture ether/petroleum ether (1/1), filtered, washed with ether and dried under vacuum to give 4-(4-bromo-2-fluoroanilino)-6-methoxy-7-(piperidin-4-ylmethoxy)quinazoline (390 mg, 70.5%).

Workup

  1. customthe volatiles were removed under vacuum
  2. customThe residue was triturated with a mixture of water/ether
  3. customThe organic layer was separated
  4. washThe aqueous layer was washed again with ether
  5. extractionThe aqueous layer was extracted with methylene chloride
  6. dry with materialThe organic layer was dried (MgSO4)
  7. customthe solvent was removed under vacuum
  8. customThe solid was triturated with a mixture ether/petroleum ether (1/1)
  9. filtrationfiltered
  10. washwashed with ether
  11. customdried under vacuum

Sources & evidence

ORD record
ord-ce86faf60a7348cd82afa4d338df2066
Source dataset
uspto-grants-2015_05
Patent number
US09040548B2

Linked notes

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