Trifluoroacetic acid → HCID 67415388, compound

HRID 1175075Notes

Reaction equation

HRID 1175075 reaction equation
FC(F)(F)C(O)=O.[Cl:8][C:9]1[C:10]([F:42])=[C:11]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:28][CH:29]4[CH2:34][CH2:33][N:32](C(OC(C)(C)C)=O)[CH2:31][CH2:30]4)=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[CH:12]=[CH:13][CH:14]=1>C(Cl)Cl.C([SiH](CC)CC)C>[ClH:8].[ClH:8].[Cl:8][C:9]1[C:10]([F:42])=[C:11]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:28][CH:29]4[CH2:34][CH2:33][NH:32][CH2:31][CH2:30]4)=[C:23]([O:26][CH3:27])[CH:24]=3)[N:19]=[CH:18][N:17]=2)[CH:12]=[CH:13][CH:14]=1

Participants

5

Reactant 2

HCID 6422Trifluoroacetic acidHCID 67415632HCID 67415632, compound

Product 1

HCID 67415388HCID 67415388, compoundYield 317.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 12052TriethylsilaneSolvent

Procedure

Trifluoroacetic acid (50 mL) was added to a solution of tert-butyl 4-({4-[(3-chloro-2-fluorophenyl)amino]-6-methoxyquinazolin-7-yl}oxy)piperidine-1-carboxylate (750 m g, 1.49 mmol) in methylene chloride (1 mL) and Triethylsilane (1 mL) and the solution stirred for 1 hour. The reaction mixture was then evaporated under reduced pressure and the residues re-dissolved in EtOAc (5 mL). This solution was then treated with 1M HCl/Diethylether (1 mL) followed by more Diethylether (50 mL) to give a heavy white precipitation. The resulting solids were collected following centrifugation and dried under vacuum to give N-(3-chloro-2-fluorophenyl)-6-methoxy-7-(piperidin-4-yloxy)quinazolin-4-amine dihydrochloride 5 as an white solid (750 mg); 1H NMR Spectrum: (DMSO-d6): 2.00-2.20 (m, 2H), 2.25-2.45 (m, 2H), 3.15-3.50 (m, 4H), 4.15 (s, 3H), 5.02 (m, 1H), 7.48 (m, 1H), 7.60-7.85 m, 3H), 8.35 (s, 1H), 8.85 (s, 1H), 9.56 (bs, 2H); Mass Spectrum: (M+H)+ 403.08.

Workup

  1. customThe reaction mixture was then evaporated under reduced pressure
  2. dissolutionthe residues re-dissolved in EtOAc (5 mL)
  3. additionThis solution was then treated with 1M HCl/Diethylether (1 mL)
  4. customto give
  5. customa heavy white precipitation
  6. customThe resulting solids were collected
  7. customdried under vacuum

Sources & evidence

ORD record
ord-f8dec25fff1c4b8f896aaa8a9947069f
Source dataset
uspto-grants-2010_11
Patent number
US07838530B2

Reaction notes

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