Sodium hydride → (5,11-Dihydro-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-[4-(3-methyl-pyrazol-1-yl)-2-trifluoromethyl-phenyl]-methanone

HRID 1978179Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1978179
[H-].[Na+].[CH3:3][C:4]1[CH:8]=[CH:7][NH:6][N:5]=1.[N:9]1[C:14]2[NH:15][C:16]3[CH:36]=[CH:35][CH:34]=[CH:33][C:17]=3[N:18]([C:20]([C:22]3[CH:27]=[CH:26][C:25](F)=[CH:24][C:23]=3[C:29]([F:32])([F:31])[F:30])=[O:21])[CH2:19][C:13]=2[CH:12]=[CH:11][CH:10]=1>CCCCCC>[CH3:3][C:4]1[CH:8]=[CH:7][N:6]([C:25]2[CH:26]=[CH:27][C:22]([C:20]([N:18]3[C:17]4[CH:33]=[CH:34][CH:35]=[CH:36][C:16]=4[NH:15][C:14]4[N:9]=[CH:10][CH:11]=[CH:12][C:13]=4[CH2:19]3)=[O:21])=[C:23]([C:29]([F:30])([F:32])[F:31])[CH:24]=2)[N:5]=1

Komponenten

5

Edukt 3

HCID 24758Sodium hydrideHCID 15513330(6,11-Dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-(4-fluoro-2-trifluoromethyl-phenyl)-methanoneHCID 178428694HCID 178428694, Verbindung

Produkt 1

HCID 9824954(5,11-Dihydro-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-[4-(3-methyl-pyrazol-1-yl)-2-trifluoromethyl-phenyl]-methanoneAusbeute 79 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8058HexaneLösungsmittel

Versuchsvorschrift

Sodium hydride (60% suspension in oil, 0.83 g, 20.8 mmol) was washed once with hexane, dried under nitrogen and resuspended in dry dimethylformamide (60 mL). 3-methyl pyrazole (0.90 mL, 11.2 mmol) was added in one portion. After the gas evolution subsided the stirring was continued at room temperature. The (6,11-dihydro-5H-pyrido[2,3-b][1,5]benzodiazepin-6-yl)-(4-fluoro-2-trifluoromethylphenyl)-methanone of Step B (3.6 g, 9.3 mmol) was added in one portion and the mixture was placed in an oil bath (preheated at 130° C.) for 30 minutes. After cooling, the mixture was partitioned between water and ethyl acetate. The organic extracts were dried over sodium sulfate, and evaporated to dryness. The residue was dissolved in dichloromethane and absorbed onto a silica Merck-60 flash column. Elution with 25% ethyl acetate in hexane provided 3.3 g of the desired product as a foam which crystallized by sonication from ethanol-hexane, m.p. 212-214° C. Further elution with 30% ethyl acetate in hexane yielded the more polar 5-methylpyrazole regioisomer of Example 6.

Aufarbeitung

  1. customdried under nitrogen
  2. customwas continued at room temperature
  3. customthe mixture was placed in an oil bath
  4. temperatureAfter cooling
  5. customthe mixture was partitioned between water and ethyl acetate
  6. dry with materialThe organic extracts were dried over sodium sulfate
  7. customevaporated to dryness
  8. dissolutionThe residue was dissolved in dichloromethane
  9. customabsorbed onto a silica Merck-60 flash column
  10. washElution with 25% ethyl acetate in hexane

Quellen und Nachweise

ORD-Eintrag
ord-cfff005700be41d9832da14718025ebc
Quelldatensatz
uspto-grants-2001_05
Patentnummer
US06235900B1

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