Methanesulfonyl chloride → 4-(3-Chloro-2-fluoroanilino)-6-[1-(methylsulfonyl)piperidin-3-yloxy]-7-methoxyquinazoline

HRID 1948914Notes

Reaction equation

HRID 1948914 reaction equation
[CH3:1][S:2](Cl)(=[O:4])=[O:3].[Cl:6][C:7]1[C:8]([F:33])=[C:9]([CH:30]=[CH:31][CH:32]=1)[NH:10][C:11]1[C:20]2[C:15](=[CH:16][C:17]([O:28][CH3:29])=[C:18]([O:21][CH:22]3[CH2:27][CH2:26][CH2:25][NH:24][CH2:23]3)[CH:19]=2)[N:14]=[CH:13][N:12]=1.C(N(C(C)C)CC)(C)C>C(Cl)Cl>[Cl:6][C:7]1[C:8]([F:33])=[C:9]([CH:30]=[CH:31][CH:32]=1)[NH:10][C:11]1[C:20]2[C:15](=[CH:16][C:17]([O:28][CH3:29])=[C:18]([O:21][CH:22]3[CH2:27][CH2:26][CH2:25][N:24]([S:2]([CH3:1])(=[O:4])=[O:3])[CH2:23]3)[CH:19]=2)[N:14]=[CH:13][N:12]=1

Participants

5

Reactant 3

HCID 31297Methanesulfonyl chlorideHCID 81531DiisopropylethylamineHCID 104537624-(3-Chloro-2-fluoroanilino)-6-(piperidin-3-yloxy)-7-methoxyquinazoline

Product 1

HCID 100508524-(3-Chloro-2-fluoroanilino)-6-[1-(methylsulfonyl)piperidin-3-yloxy]-7-methoxyquinazoline

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

Methanesulfonyl chloride (42 mg) was added to a solution of 4-(3-chloro-2-fluoroanilino)-7-methoxy-6-(piperidin-3-yloxy)quinazoline (134 mg) and diisopropylethylamine (65 mg) in methylene chloride (5 ml) at ambient temperature. 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 eluting with increasingly polar mixtures of methylene chloride/methanol (100/0 to 95/5). The fractions containing the title product were combined and evaporated under vacuum and the residue triturated with diethyl ether, filtered and dried under vacuum to give the title product as a mixture of the 3R and 3S isomers (0.10 g); 1H NMR Spectrum: (DMSO d6 and CD3COOD) 1.54-2.07 (m, 4H), 2.95 (s, 3H), 3.10-120 (m, 1H), 3.21-3.37 (m, 2H), 3.50-3.59 (m, 1H), 3.93 (s, 3H), 4.70 (m, 1H), 7.20-7.29 (m, 2H), 7.40-7.55 (m, 2H), 7.89 (s, 1H), 8.37 (s, 1H); Mass Spectrum: (M+H)+ 481.

Workup

  1. customthe residue was purified by column chromatography
  2. washeluting
  3. temperaturewith increasingly polar mixtures of methylene chloride/methanol (100/0 to 95/5)
  4. additionThe fractions containing the title product
  5. customevaporated under vacuum
  6. customthe residue triturated with diethyl ether
  7. filtrationfiltered
  8. customdried under vacuum

Sources & evidence

ORD record
ord-5c82fc651e704a4bb24bb4bbf6720eca
Source dataset
uspto-grants-2013_03
Patent number
US08399667B2

Reaction notes

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