Triethylamine → 2-{4-(Aminocarbonyl)-4-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidin-1-yl}-2-oxoethyl acetate

HRID 1867683Notes

Reaction equation

HRID 1867683 reaction equation
C(N(CC)CC)C.[Cl:8][C:9]1[C:10]([F:40])=[C:11]([NH:15][C:16]2[C:25]3[C:20](=[CH:21][C:22]([O:38][CH3:39])=[C:23]([CH2:26][N:27]([CH3:37])[C:28]4([C:34]([NH2:36])=[O:35])[CH2:33][CH2:32][NH:31][CH2:30][CH2:29]4)[CH:24]=3)[N:19]=[CH:18][N:17]=2)[CH:12]=[CH:13][CH:14]=1.[C:41]([O:44][CH2:45][C:46](Cl)=[O:47])(=[O:43])[CH3:42]>CN1C(=O)CCC1>[C:41]([O:44][CH2:45][C:46]([N:31]1[CH2:32][CH2:33][C:28]([C:34]([NH2:36])=[O:35])([N:27]([CH2:26][C:23]2[CH:24]=[C:25]3[C:20](=[CH:21][C:22]=2[O:38][CH3:39])[N:19]=[CH:18][N:17]=[C:16]3[NH:15][C:11]2[CH:12]=[CH:13][CH:14]=[C:9]([Cl:8])[C:10]=2[F:40])[CH3:37])[CH2:29][CH2:30]1)=[O:47])(=[O:43])[CH3:42]

Participants

5

Reactant 3

HCID 8471TriethylamineHCID 26297Acetoxyacetyl chlorideHCID 57979867HCID 57979867, compound

Product 1

HCID 690489122-{4-(Aminocarbonyl)-4-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidin-1-yl}-2-oxoethyl acetate

Reagents, catalysts & solvents 1

HCID 13387N-methyl-2-pyrrolidoneSolvent

Procedure

Triethylamine (360 μl, 2.58 mmol) was added to a stirred, cooled (0° C.) suspension of 4-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidine-4-carboxamide (300 mg, 0.63 mmol) (Example 16) in NMP (5 ml). Acetoxyacetyl chloride (100 μl 0.93 mmol) was then added drop wise and the reaction mixture left to warm to room temperature over a period of 2 hours. This was then partitioned between saturated aqueous sodium hydrogen carbonate solution and ethyl acetate. The organic phase was washed with saturated aqueous ammonium chloride solution followed by brine, dried over magnesium sulfate, filtered and evaporated to give 2-{4-(aminocarbonyl)-4-[({4-[(3-chloro-2-fluorophenyl)amino]-7-methoxyquinazolin-6-yl}methyl)(methyl)amino]piperidin-1-yl}-2-oxoethyl acetate as a dry film (250 mg). Mass spectrum: (M+H)+ 573.

Workup

  1. temperaturecooled
  2. waitthe reaction mixture left
  3. customThis was then partitioned between saturated aqueous sodium hydrogen carbonate solution and ethyl acetate
  4. washThe organic phase was washed with saturated aqueous ammonium chloride solution
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated

Sources & evidence

ORD record
ord-b62e641a614149b19b739e3c28282ceb
Source dataset
uspto-grants-2009_12
Patent number
US07632840B2

Reaction notes

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