Dimethylformamide → 4-[1-(Cyano-methyl-methyl)-6-nitro-1H-indol-3-yl]-2-fluoro-benzonitrile

HRID 2079897

Reaktionsgleichung

Reaktionsgleichung von HRID 2079897
[F:1][C:2]1[CH:9]=[C:8]([C:10]2[C:18]3[C:13](=[CH:14][C:15]([N+:19]([O-:21])=[O:20])=[CH:16][CH:17]=3)[NH:12][CH:11]=2)[CH:7]=[CH:6][C:3]=1[C:4]#[N:5].C(=O)([O-])[O-].[Cs+].[Cs+].CN(C)C=O.[C:33]([CH:35](OS(C1C=CC(C)=CC=1)(=O)=O)[CH3:36])#[N:34]>O.[Cl-].[Na+].O.C(OCC)(=O)C>[C:33]([CH:35]([CH3:36])[N:12]1[C:13]2[C:18](=[CH:17][CH:16]=[C:15]([N+:19]([O-:21])=[O:20])[CH:14]=2)[C:10]([C:8]2[CH:7]=[CH:6][C:3]([C:4]#[N:5])=[C:2]([F:1])[CH:9]=2)=[CH:11]1)#[N:34]

Komponenten

8

Edukt 4

HCID 6228DimethylformamideHCID 10796Cesium carbonateHCID 140143101-Cyanoethyl 4-methylbenzene-1-sulfonateHCID 574421952-Fluoro-4-(6-nitro-1H-indol-3-yl)-benzonitrile

Produkt 1

HCID 671006464-[1-(Cyano-methyl-methyl)-6-nitro-1H-indol-3-yl]-2-fluoro-benzonitrileAusbeute 47,3 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 962WaterLösungsmittelHCID 8857Ethyl AcetateLösungsmittelHCID 57417360Sodium chloride; waterLösungsmittel

Versuchsvorschrift

Method LL Add 2-Fluoro-4-(6-nitro-1H-indol-3-yl)-benzonitrile (1.24 mmoles; 350 mg), cesium carbonate (3.61 mmoles; 1.18 g) and dimethylformamide (10 mL) to a reaction vessel equipped with a stir bar. Stir this mixture for 10 minutes at room temperature then add toluene-4-sulfonic acid cyano-methyl-methyl ester (3.11 mmoles; 701 mg). Stir the resulting mixture for 5 hours at 55° C. Dilute this material with water (25 mL), brine (50 mL) and ethyl acetate (50 mL). Separate the organics and extract the resulting aqueous mixture with ethyl acetate (2×) and dichloromethane containing 10% methanol (2×). Combine the organics and concentrate in vacuo to about ½ volume. Wash the resulting mixture with water and evaporate the solvent in vacuo. Triturate the resulting yellow solids with hot dichloromethane. Collect the solids by vacuum filtration and rinse them with 50% dichloromethane/hexane to give the title compound (196 mg, 47%) yellow amorphous solid. MS (IS−) m/e 333.0 (M−1), 393.0 (M−1+OAc).

Aufarbeitung

  1. customequipped with a stir bar
  2. stirringStir the resulting mixture for 5 hours at 55° C
  3. customSeparate the organics and
  4. extractionextract the resulting aqueous mixture with ethyl acetate (2×) and dichloromethane containing 10% methanol (2×)
  5. concentrationCombine the organics and concentrate in vacuo to about ½ volume
  6. washWash the resulting mixture with water
  7. customevaporate the solvent in vacuo
  8. customTriturate the resulting yellow solids with hot dichloromethane
  9. customCollect the solids
  10. filtrationby vacuum filtration
  11. washrinse them with 50% dichloromethane/hexane

Quellen und Nachweise

ORD-Eintrag
ord-a1cae73f246748bc8eb63bbd10bbed85
Quelldatensatz
uspto-grants-2011_04
Patentnummer
US07932284B2

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