Chloroacetyl chloride → 6-[1-(Chloroacetyl)piperidin-3-yloxy]4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline

HRID 1948926Notes

Reaction equation

HRID 1948926 reaction equation
[Cl:1][C:2]1[C:3]([F:28])=[C:4]([CH:25]=[CH:26][CH:27]=1)[NH:5][C:6]1[C:15]2[C:10](=[CH:11][C:12]([O:23][CH3:24])=[C:13]([O:16][CH:17]3[CH2:22][CH2:21][CH2:20][NH:19][CH2:18]3)[CH:14]=2)[N:9]=[CH:8][N:7]=1.[Cl:29][CH2:30][C:31](Cl)=[O:32].C(N(CC)C(C)C)(C)C>C(Cl)Cl>[Cl:29][CH2:30][C:31]([N:19]1[CH2:20][CH2:21][CH2:22][CH:17]([O:16][C:13]2[CH:14]=[C:15]3[C:10](=[CH:11][C:12]=2[O:23][CH3:24])[N:9]=[CH:8][N:7]=[C:6]3[NH:5][C:4]2[CH:25]=[CH:26][CH:27]=[C:2]([Cl:1])[C:3]=2[F:28])[CH2:18]1)=[O:32]

Participants

5

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 81531DiisopropylethylamineHCID 104537624-(3-Chloro-2-fluoroanilino)-6-(piperidin-3-yloxy)-7-methoxyquinazoline

Product 1

HCID 685236386-[1-(Chloroacetyl)piperidin-3-yloxy]4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolineYield 91.6%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

The 6-[1-(chloroacetyl)piperidin-3-yloxy]-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline material was prepared as follows: —4-(3-chloro-2-fluoroanilino)-7-methoxy-6-(piperidin-3-yloxy)quinazoline (430 mg, 1.07 mmol) (Prepared as described in Example 22 under preparation of starting material), chloroacetyl chloride (126 mg, 1.12 mmol) and N,N-diisopropylethylamine (519 mg, 4.02 mmol) in methylene chloride (15 ml) was stirred at room temperature for 2 hours. The solvent was evaporated under vacuum and the residue purified by column chromatography eluting with methylene chloride/methanol (saturated with ammonia) (92/8) solvent, Removal of the solvent under vacuum gave 6-[1-(chloroacetyl)piperidin-3-yloxy]-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline as a yellow gum (470 mg). This material was used without any further purification); Mass Spectrum: (M+H)+ 479.

Workup

  1. customThe 6-[1-(chloroacetyl)piperidin-3-yloxy]-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline material was prepared
  2. customThe solvent was evaporated under vacuum
  3. customthe residue purified by column chromatography
  4. washeluting with methylene chloride/methanol (saturated with ammonia) (92/8) solvent, Removal of the solvent under vacuum

Sources & evidence

ORD record
ord-dcff47e93f9948e18a52a21aa6b93453
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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