Acetyl chloride → 6-(1-Acetylpiperidin-3-yloxy)-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline

HRID 1948919Notes

Reaction equation

HRID 1948919 reaction equation
[C:1](Cl)(=[O:3])[CH3:2].[Cl:5][C:6]1[C:7]([F:32])=[C:8]([CH:29]=[CH:30][CH:31]=1)[NH:9][C:10]1[C:19]2[C:14](=[CH:15][C:16]([O:27][CH3:28])=[C:17]([O:20][CH:21]3[CH2:26][CH2:25][CH2:24][NH:23][CH2:22]3)[CH:18]=2)[N:13]=[CH:12][N:11]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[C:1]([N:23]1[CH2:24][CH2:25][CH2:26][CH:21]([O:20][C:17]2[CH:18]=[C:19]3[C:14](=[CH:15][C:16]=2[O:27][CH3:28])[N:13]=[CH:12][N:11]=[C:10]3[NH:9][C:8]2[CH:29]=[CH:30][CH:31]=[C:6]([Cl:5])[C:7]=2[F:32])[CH2:22]1)(=[O:3])[CH3:2]

Participants

5

Reactant 3

HCID 6367Acetyl chlorideHCID 81531DiisopropylethylamineHCID 104537624-(3-Chloro-2-fluoroanilino)-6-(piperidin-3-yloxy)-7-methoxyquinazoline

Product 1

HCID 104336166-(1-Acetylpiperidin-3-yloxy)-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolineYield 47.3%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Acetyl chloride (27 mg) was added to a solution of 4-(3-chloro-2-fluoroanilino)-6-(piperidin-3-yloxy)-7-methoxyquinazoline (starting material described in Example 22; 134 mg) and diisopropylethylamine (65 mg) in methylene chloride (5 ml) and the reaction mixture was stirred at ambient temperature for 16 hours. The reaction mixture was adsorbed onto silica and purified by column chromatography eluting with increasingly polar mixtures of methylene chloride/methanol (100/0 to 95/5). The fractions containing the required product were combined and evaporated to give the title product (0.07 g); 1H NMR Spectrum: (DMSO d6 at 373K) 1.52-1.62 (m, 1H), 1.80-1.94 (m, 2H), 2.00 (s, 3H), 2.06-2.15 (m, 1H), 3.43-3.64 (m, 3H), 3.82-4.04 (m, 4H), 4.58 (m, 1H), 7.20-7.29 (m, 2H), 7.42 (t, 1H), 7.59 (t, 1H), 7.93 (s, 1H), 8.40 (s, 1H), 9.30 (s, 1H); Mass Spectrum: (M+H)+ 445.

Workup

  1. custompurified by column chromatography
  2. washeluting
  3. temperaturewith increasingly polar mixtures of methylene chloride/methanol (100/0 to 95/5)
  4. additionThe fractions containing the required product
  5. customevaporated

Sources & evidence

ORD record
ord-f7883addf33743ef88f7075bc0adc9cb
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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