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

HRID 1948914ノート

反応式

HRID 1948914 の反応式
[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

参加物

5

反応物 3

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6344Dichloromethane溶媒

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-5c82fc651e704a4bb24bb4bbf6720eca
出典データセット
uspto-grants-2013_03
特許番号
US08399667B2

反応ノート

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