Sodium Cyanide → 3-[5-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,3-thiazol-2-yl]pentanedinitrile

HRID 1501411Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1501411
O[CH2:2][CH:3]([C:7]1[S:8][C:9]([C:12]2[C:13]3[CH:20]=[CH:19][N:18](COCC[Si](C)(C)C)[C:14]=3[N:15]=[CH:16][N:17]=2)=[CH:10][N:11]=1)[CH2:4][C:5]#[N:6].CS(Cl)(=O)=O.[C-:34]#[N:35].[Na+]>C(Cl)Cl.O>[N:15]1[C:14]2[NH:18][CH:19]=[CH:20][C:13]=2[C:12]([C:9]2[S:8][C:7]([CH:3]([CH2:2][C:34]#[N:35])[CH2:4][C:5]#[N:6])=[N:11][CH:10]=2)=[N:17][CH:16]=1

Komponenten

6

Edukt 3

HCID 8929Sodium CyanideHCID 31297Methanesulfonyl chlorideHCID 574780724-hydroxy-3-[5-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,3-thiazol-2-yl]butanenitrile

Produkt 1

HCID 177549033-[5-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,3-thiazol-2-yl]pentanedinitrileAusbeute 7 %

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 962WaterLösungsmittel2×HCID 6344DichloromethaneLösungsmittel

Versuchsvorschrift

A solution of the above prepared 4-hydroxy-3-[5-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,3-thiazol-2-yl]butanenitrile in DCM (12 mL) at 0° C. was treated sequentially with TEA (130 μL, 0.94 mmol) and methanesulfonyl chloride (73 μL, 0.94 mmol). After 1 hour reaction time, the mixture was diluted with water and extracted with ethyl acetate three times. The extracts were washed with water and brine, dried over sodium sulfate, filtered and concentrated in vacuo. The residue was then dissolved in DMSO (5 mL) and sodium cyanide (110 mg, 2.3 mmol) was added. After 30 minutes, the mixture was diluted with water, extracted with ether, washed with water, brine and dried over sodium sulfate. Concentration and purification by flash column chromatography (ethyl acetate/hexanes) afforded the desired product (14 mg, 7%). MS(ES): 425(M+1).

Aufarbeitung

  1. customAfter 1 hour reaction time
  2. extractionextracted with ethyl acetate three times
  3. washThe extracts were washed with water and brine
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo
  7. dissolutionThe residue was then dissolved in DMSO (5 mL)
  8. extractionextracted with ether
  9. washwashed with water, brine
  10. dry with materialdried over sodium sulfate
  11. concentrationConcentration and purification by flash column chromatography (ethyl acetate/hexanes)

Quellen und Nachweise

ORD-Eintrag
ord-c63926ab4cd74a03a1e5bba24798f555
Quelldatensatz
uspto-grants-2015_12
Patentnummer
US09206187B2

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