Diisopropylethylamine → 6-[1-(N,N-Dimethylsulfamoyl)piperidin-4-yloxy]-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline

HRID 1948909Notes

Reaction equation

HRID 1948909 reaction equation
[CH3:1][N:2]([CH3:7])[S:3](Cl)(=[O:5])=[O:4].Cl.Cl.[NH:10]1[CH2:15][CH2:14][CH:13]([O:16][C:17]2[CH:18]=[C:19]3[C:24](=[CH:25][C:26]=2[O:27][CH3:28])[N:23]=[CH:22][N:21]=[C:20]3[NH:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[C:31]=2[F:37])[CH2:12][CH2:11]1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[CH3:1][N:2]([CH3:7])[S:3]([N:10]1[CH2:15][CH2:14][CH:13]([O:16][C:17]2[CH:18]=[C:19]3[C:24](=[CH:25][C:26]=2[O:27][CH3:28])[N:23]=[CH:22][N:21]=[C:20]3[NH:29][C:30]2[CH:35]=[CH:34][CH:33]=[C:32]([Cl:36])[C:31]=2[F:37])[CH2:12][CH2:11]1)(=[O:5])=[O:4]

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 83372Dimethylsulphamoyl chlorideHCID 574768654-(3-Chloro-2-fluoroanilino)-7-methoxy-6-(piperidin-4-yloxy)quinazoline dihydrochloride

Product 1

HCID 104363476-[1-(N,N-Dimethylsulfamoyl)piperidin-4-yloxy]-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazolineYield 85.8%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Dimethylsulfamoyl chloride (90 mg) was added to a solution of 6-(piperidin-4-yloxy)-4-(3-chloro-2-fluoroanilino)-7-methoxyquinazoline dihydrochloride (250 mg) (starting material Example 16) and diisopropylethylamine (184 mg) in methylene chloride (10 ml). The reaction mixture was stirred for 16 hours at ambient temperature. The reaction mixture was adsorbed onto silica and the residue was purified by column chromatography on silica eluting with increasingly polar mixtures of methylene chloride/methanol (100/0 to 95/5). The fractions containing the expected product were combined and evaporated under vacuum and the residue triturated with diethylether to give the title product as a white solid (0.23 g); 1H NMR. Spectrum: (DMSO d6) 1.72-1.86 (m, 2H), 2.00-2.12 (m, 2H), 2.76 (s, 6H); 3.12-3.23 (m, 2H), 3.40-3.51 (m, 2H), 3.94 (s, 3H), 4.68 (m, 1H), 7.19-7.30 (m, 2H), 7.43-7.54 (m, 2H), 7.85 (s, 1H), 8.37 (s, 1H), 9.52 (s, 1H); Mass Spectrum: (M+H)+ 510.

Workup

  1. customthe residue was purified by column chromatography on silica eluting
  2. temperaturewith increasingly polar mixtures of methylene chloride/methanol (100/0 to 95/5)
  3. additionThe fractions containing the expected product
  4. customevaporated under vacuum
  5. customthe residue triturated with diethylether

Sources & evidence

ORD record
ord-2571d509e80b4eca8f0111f82db9e086
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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