Sodium hydride → HCID 10145805, Verbindung

HRID 2085098

Reaktionsgleichung

Reaktionsgleichung von HRID 2085098
[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([S:10]([NH:13][C:14]2[C:19]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[O:27][CH3:28])=[C:18]([O:29][CH2:30][C:31]#[C:32][CH2:33][OH:34])[N:17]=[CH:16][N:15]=2)(=[O:12])=[O:11])=[N:8][CH:9]=1)([CH3:3])[CH3:2].[H-].[Na+].[CH3:37][O:38][C:39]1[CH:44]=[C:43]([O:45][CH3:46])[N:42]=[C:41](S(C)(=O)=O)[N:40]=1>C1COCC1>[NH3:8].[CH:1]([C:4]1[CH:5]=[CH:6][C:7]([S:10]([NH:13][C:14]2[C:19]([O:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[O:27][CH3:28])=[C:18]([O:29][CH2:30][C:31]#[C:32][CH2:33][O:34][C:41]3[N:42]=[C:43]([O:45][CH3:46])[CH:44]=[C:39]([O:38][CH3:37])[N:40]=3)[N:17]=[CH:16][N:15]=2)(=[O:12])=[O:11])=[N:8][CH:9]=1)([CH3:3])[CH3:2]

Komponenten

6

Edukt 3

HCID 24758Sodium hydrideHCID 8383634,6-Dimethoxy-2-(methylsulfonyl)pyrimidineHCID 101408715-isopropyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(o-methoxyphenoxy)-4-pyrimidinyl]-2-pyridine sulfonamide

Produkt 2

HCID 222AmmoniaHCID 10145805HCID 10145805, VerbindungAusbeute 44,2 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8028TetrahydrofuranLösungsmittel

Versuchsvorschrift

To a solution of 250 mg of 5-isopropyl-N-[6-(4-hydroxy-2-butynyloxy)-5-(o-methoxyphenoxy)-4-pyrimidinyl]-2-pyridine sulfonamide (Example 13) in 15 ml of THF was added 48 mg of NaH. The mixture was stirred for 2 h at room temperature before 120 mg of 4,6-dimethoxy-2-methylsulfonylpyrimidine was added. Stirring was continued for 16 h at reflux. Eventually, the solvent was evaporated and the remaining residue was partitioned between 50 ml of 10% aqueous citric acid and 50 ml of ethyl acetate. The organic layer was separated and the aqueous layer was extracted two more times with 50 ml of ethyl acetate. The combined organic layers were washed with water and brine, dried over MgSO4 and evaporated. The crude product was purified by chromatography on prep. tlc-plates coated with silica gel with ethyl acetate:methanol: sat. aqueous ammonia 8:2:1 to give 71 mg of 5-isopropyl-N-[6-(4-(4,6-dimethoxy-2-pyrimidinyloxy)-2-butynyloxy)-5-(o-methoxyphenoxy)-4-pyrimidinyl]-2-pyridine sulfonamide as a beige foam. LC-MS: tR=5.50 min, [M+1]+=623.29, [M−1]+=621.40.

Aufarbeitung

  1. additionwas added
  2. temperatureat reflux
  3. customEventually, the solvent was evaporated
  4. customthe remaining residue was partitioned between 50 ml of 10% aqueous citric acid and 50 ml of ethyl acetate
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted two more times with 50 ml of ethyl acetate
  7. washThe combined organic layers were washed with water and brine
  8. dry with materialdried over MgSO4
  9. customevaporated
  10. customThe crude product was purified by chromatography on prep

Quellen und Nachweise

ORD-Eintrag
ord-a4743327dc0a43289390ad90d9a8acd7
Quelldatensatz
uspto-grants-2004_04
Patentnummer
US06720322B2

Verknüpfte Notizen

Wird geladen…