Methanol → 3-{1-[4-(7-{[2-(Trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]but-3-yn-1-yl}benzonitrile

HRID 45024

Reaktionsgleichung

Reaktionsgleichung von HRID 45024
[H-].[CH2:2]([Al+]CC(C)C)C(C)C.[C:11]([C:13]1[CH:14]=[C:15]([CH:19]([N:25]2[CH:29]=[C:28]([C:30]3[C:31]4[CH:38]=[CH:37][N:36]([CH2:39][O:40][CH2:41][CH2:42][Si:43]([CH3:46])([CH3:45])[CH3:44])[C:32]=4[N:33]=[CH:34][N:35]=3)[CH:27]=[N:26]2)[CH2:20][C:21](OC)=O)[CH:16]=[CH:17][CH:18]=1)#[N:12].C(Cl)Cl.CO.C(=O)([O-])[O-].[K+].[K+].C/C(/[O-])=C(/P(OC)(OC)=O)\[N+]#N>CCCCCC>[CH3:45][Si:43]([CH3:46])([CH3:44])[CH2:42][CH2:41][O:40][CH2:39][N:36]1[C:32]2[N:33]=[CH:34][N:35]=[C:30]([C:28]3[CH:27]=[N:26][N:25]([CH:19]([C:15]4[CH:14]=[C:13]([CH:18]=[CH:17][CH:16]=4)[C:11]#[N:12])[CH2:20][C:21]#[CH:2])[CH:29]=3)[C:31]=2[CH:38]=[CH:37]1

Komponenten

8

Edukt 6

HCID 887MethanolHCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 21225700DiisobutylaluminumhydrideHCID 57477994methyl 3-(3-cyanophenyl)-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanoateHCID 178502985HCID 178502985, Verbindung

Produkt 1

HCID 574779953-{1-[4-(7-{[2-(Trimethylsilyl)ethoxy]methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]but-3-yn-1-yl}benzonitrile

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 8058HexaneLösungsmittel

Reaktionsbedingungen

Temperatur
-78 °C

Versuchsvorschrift

1 M Diisobutylaluminum hydride in hexane (0.31 mL) was added dropwise to a solution of methyl 3-(3-cyanophenyl)-3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]propanoate (100 mg, 0.0002 mol) (prepared by using a procedure analogous to Example 712, Step 1) in DCM (3 mL, 0.05 mol) and the mixture was cooled to −78° C. The reaction mixture was stirred at −78° C. for 4 h and was afterward quenched with cold methanol (3 mL, 0.07 mol). The reaction was allowed to warm to 0° C. and potassium carbonate (60 mg, 0.0004 mol) and Bestmann-Ohira reagent (1.5 eq, 57 mg) (E. Quesada et al, Tetrahedron, 62 (2006) 6673-6680) were added. The reaction was stirred at room temperature overnight, and then partitioned between ethyl acetate and water. The organic layer was washed with saturated NaCl, dried over MgSO4, filtered and concentrated to give the crude product. The crude product was purified using silica gel (EtOAC/Hexane 1:3 to 1:1) to give the desired product, 3-{1-[4-(7-{[2-(trimethylsilyl)ethoxy]-methyl}-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]but-3-yn-1-yl}benzonitrile (40 mg of mixture). m/z=469 (M+1).

Aufarbeitung

  1. customprepared
  2. temperatureto warm to 0° C.
  3. stirringThe reaction was stirred at room temperature overnight
  4. custompartitioned between ethyl acetate and water
  5. washThe organic layer was washed with saturated NaCl
  6. dry with materialdried over MgSO4
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customto give the crude product
  10. customThe crude product was purified

Quellen und Nachweise

ORD-Eintrag
ord-e319a156723d450da269dfb9f8b8eff6
Quelldatensatz
uspto-grants-2013_09
Patentnummer
US08541425B2

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