Methanesulfonyl chloride → HCID 9982010, Verbindung

HRID 1948928Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1948928
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

Komponenten

6

Edukt 2

HCID 31297Methanesulfonyl chlorideHCID 68522948HCID 68522948, Verbindung

Produkt 1

HCID 9982010HCID 9982010, VerbindungAusbeute 520,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 1049PyridineLösungsmittelHCID 6344DichloromethaneLösungsmittelHCID 81531DiisopropylethylamineLösungsmittel

Versuchsvorschrift

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.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-56a240c7b6234da6a92300e5c182fdf4
Quelldatensatz
uspto-grants-2013_03
Patentnummer
US08399667B2

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