Methanesulfonyl chloride → HCID 9982010、化合物

HRID 1948928ノート

反応式

HRID 1948928 の反応式
Cl.[Cl:2][C:3]1[C:4]([F:28])=[C:5]([CH:25]=[CH:26][CH:27]=1)[NH:6][C:7]1[C:16]2[C:11](=[CH:12][C:13]([O:23][CH3:24])=[C:14]([O:17][C@@H:18]3[CH2:22][CH2:21][NH:20][CH2:19]3)[CH:15]=2)[N:10]=[CH:9][N:8]=1.[CH3:29][S:30](Cl)(=[O:32])=[O:31]>ClCCl.N1C=CC=CC=1.C(N(C(C)C)CC)(C)C>[Cl:2][C:3]1[C:4]([F:28])=[C:5]([CH:25]=[CH:26][CH:27]=1)[NH:6][C:7]1[C:16]2[C:11](=[CH:12][C:13]([O:23][CH3:24])=[C:14]([O:17][C@@H:18]3[CH2:22][CH2:21][N:20]([S:30]([CH3:29])(=[O:32])=[O:31])[CH2:19]3)[CH:15]=2)[N:10]=[CH:9][N:8]=1

参加物

6

反応物 2

HCID 31297Methanesulfonyl chlorideHCID 68522948HCID 68522948、化合物

生成物 1

HCID 9982010HCID 9982010、化合物収率 520.1%

試薬・触媒・溶媒 3

HCID 1049Pyridine溶媒HCID 6344Dichloromethane溶媒HCID 81531Diisopropylethylamine溶媒

実験手順

4-(3-chloro-2-fluoroanilino)-6-[(3R)-pyrrolidin-3-yloxy]-7-methoxyquinazoline hydrochloride (0.21 g, 0.49 mmole) was dissolved in a mixture of dichloromethane (4 ml), pyridine (1 ml) and diisopropylethylamine (0.17 ml) under a nitrogen atmosphere. Methanesulfonyl chloride (0.06 ml, 0.07 mmol) was added to the stirred solution. After stirring 2 hours at room temperature, the reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered and evaporated. The residue was purified by column chromatography eluting with methylene chloride/methanol (saturated with ammonia) (96/4). The fractions containing the expected product were combined and evaporated under vacuum and the residual gum was triturated with diethylether, filtered and dried under vacuum to give the title product as a white solid (0.17 g, 74%); 1H NMR Spectrum: (DMSO d6) 2.18-2.37 (m, 2H); 2.93 (s, 3H); 3.33-3.45 (m, 2H); 3.5 (d, 1H); 3.69 (dd, 1H); 3.92 (s, 3H); 5.17 (m, 1H); 7.15-7.35 (m, 2H); 7.40-7.60 (m, 2H); 7.5 (m, 2H); 7.80 (s, 1H); 8.37 (s, 1H); 9.6 (s, 1H); Mass Spectrum: (M+H)+ 467.

後処理

  1. customthe reaction mixture was partitioned between ethyl acetate and saturated aqueous sodium bicarbonate
  2. washThe organic layer was washed with brine
  3. dry with materialdried over anhydrous sodium sulfate
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by column chromatography
  7. washeluting with methylene chloride/methanol (saturated with ammonia) (96/4)
  8. additionThe fractions containing the expected product
  9. customevaporated under vacuum
  10. customthe residual gum was triturated with diethylether
  11. filtrationfiltered
  12. customdried under vacuum

出典と根拠

ORDレコード
ord-56a240c7b6234da6a92300e5c182fdf4
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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