Trifluoroacetic acid → N-(5-chloro-1,3-benzodioxol-4-yl)-7-methoxy-5-(piperidin-4-yloxy)quinazolin-4-amine

HRID 1826305Notes

Reaction equation

HRID 1826305 reaction equation
Cl.Cl.C(OC([N:10]1[CH2:15][CH2:14][CH:13]([O:16][C:17]2[CH:26]=[C:25]([O:27][CH3:28])[CH:24]=[C:23]3[C:18]=2[C:19]([NH:29][C:30]2[C:35]([Cl:36])=[CH:34][CH:33]=[C:32]4[O:37][CH2:38][O:39][C:31]=24)=[N:20][CH:21]=[N:22]3)[CH2:12][CH2:11]1)=O)(C)(C)C.FC(F)(F)C(O)=O>C(Cl)Cl>[Cl:36][C:35]1[C:30]([NH:29][C:19]2[C:18]3[C:23](=[CH:24][C:25]([O:27][CH3:28])=[CH:26][C:17]=3[O:16][CH:13]3[CH2:12][CH2:11][NH:10][CH2:15][CH2:14]3)[N:22]=[CH:21][N:20]=2)=[C:31]2[O:39][CH2:38][O:37][C:32]2=[CH:33][CH:34]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 221408065-(1-Tert-butoxycarbonylpiperidin-4-yloxy)-4-(6-chloro-2,3-methylenedioxyanilino)-7-methoxyquinazoline dihydrochloride

Product 1

HCID 10274208N-(5-chloro-1,3-benzodioxol-4-yl)-7-methoxy-5-(piperidin-4-yloxy)quinazolin-4-amineYield 84.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

A mixture of 5-(1-tert-butoxycarbonylpiperidin-4-yloxy)-4-(6-chloro-2,3-methylenedioxyanilino)-7-methoxyquinazoline dihydrochloride (2.39 g), trifluoroacetic acid (10 ml) and methylene chloride (35 ml) was stirred at ambient temperature for 1.5 hours. The mixture was evaporated and the residue was partitioned between ethyl acetate and a 1N aqueous sodium hydroxide solution. The organic layer was washed with water and brine, dried over magnesium sulphate and evaporated. The residue was purified by column chromatography on silica using a 19:1 mixture of methylene chloride and methanol as eluent. There was thus obtained the title compound (1.44 g); NMR Spectrum: (CDCl3) 1.8–2.0 (m, 2H), 2.15–2.3 (m, 2H), 2.75–2.9 (m, 2H), 3.1–3.2 (m, 2H), 3.9 (s, 3H), 4.65 (m, 1H), 6.0 (s, 2H), 6.46 (d, 1H), 6.72 (d, 1H), 6.8 (d, 1H), 6.91 (d, 1H), 8.5 (s, 1H), 9.21 (s, 1H); Mass Spectrum: M+H+ 429 and 431.

Workup

  1. customThe mixture was evaporated
  2. customthe residue was partitioned between ethyl acetate
  3. washThe organic layer was washed with water and brine
  4. dry with materialdried over magnesium sulphate
  5. customevaporated
  6. customThe residue was purified by column chromatography on silica using
  7. additiona 19:1 mixture of methylene chloride and methanol as eluent

Sources & evidence

ORD record
ord-b2ff3c596195486cbcc2429bf3aeea19
Source dataset
uspto-grants-2006_05
Patent number
US07049438B2

Reaction notes

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