Trifluoroacetic acid → 4-[({4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidine-4-carboxamide hydrochloride

HRID 1867724Notes

Reaction equation

HRID 1867724 reaction equation
FC(F)(F)C(O)=O.[NH2:8][C:9]([C:11]1([N:24]([CH2:26][C:27]2[CH:28]=[C:29]3[C:34](=[CH:35][C:36]=2[O:37][CH3:38])[N:33]=[CH:32][N:31]=[C:30]3[NH:39][C:40]2[CH:45]=[CH:44][CH:43]=[C:42]([Cl:46])[C:41]=2[F:47])[CH3:25])[CH2:16][CH2:15][N:14](C(OC(C)(C)C)=O)[CH2:13][CH2:12]1)=[O:10]>ClCCl>[ClH:46].[Cl:46][C:42]1[C:41]([F:47])=[C:40]([NH:39][C:30]2[C:29]3[C:34](=[CH:35][C:36]([O:37][CH3:38])=[C:27]([CH2:26][N:24]([CH3:25])[C:11]4([C:9]([NH2:8])=[O:10])[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]4)[CH:28]=3)[N:33]=[CH:32][N:31]=2)[CH:45]=[CH:44][CH:43]=1

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 69045783Tert-butyl 4-(aminocarbonyl)-4-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidine-1-carboxylate

Product 1

HCID 690487244-[({4-[(3-Chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidine-4-carboxamide hydrochlorideYield 224.5%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Trifluoroacetic acid (1 ml) was added to a stirred solution of tert-butyl 4-(aminocarbonyl)-4-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidine-1-carboxylate (0.35 g, 0.612 mmol) in dichloromethane (1 ml) at room temperature. The resulting solution was stirred for 1 hour, concentrated to dryness and the residue re-dissolved in dichloromethane (1 ml). 4.0 M hydrogen chloride in dioxane (1 ml) was then added to give a white precipitate. This was collected by filtration, washed with diethyl ether (2×10 ml) and dried to a constant weight to give 4-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidine-4-carboxamide hydrochloride (0.35 g, 100%), as a white solid; Mass Spectrum: (M+H)+ 473.

Workup

  1. concentrationconcentrated to dryness
  2. dissolutionthe residue re-dissolved in dichloromethane (1 ml)
  3. addition4.0 M hydrogen chloride in dioxane (1 ml) was then added
  4. customto give a white precipitate
  5. filtrationThis was collected by filtration
  6. washwashed with diethyl ether (2×10 ml)
  7. customdried to a constant weight

Sources & evidence

ORD record
ord-49d81594bab4418683665596561f6a66
Source dataset
uspto-grants-2009_12
Patent number
US07632840B2

Reaction notes

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