Cyclobutanone → 1-(1-(5-chloro-2-(1-methyl-1H-pyrazol-4-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-4-yl)cyclobutanol

HRID 2362720Notes

Reaction equation

HRID 2362720 reaction equation
Br[C:2]1[CH:3]=[N:4][N:5]([C:7]2[C:12]([Cl:13])=[CH:11][N:10]=[C:9]3[N:14]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[C:15]([C:17]4[CH:18]=[N:19][N:20]([CH3:22])[CH:21]=4)=[CH:16][C:8]=23)[CH:6]=1.C([Li])CCC.[C:36]1(=[O:40])[CH2:39][CH2:38][CH2:37]1>O1CCCC1>[Cl:13][C:12]1[C:7]([N:5]2[CH:6]=[C:2]([C:36]3([OH:40])[CH2:39][CH2:38][CH2:37]3)[CH:3]=[N:4]2)=[C:8]2[CH:16]=[C:15]([C:17]3[CH:18]=[N:19][N:20]([CH3:22])[CH:21]=3)[N:14]([CH2:23][O:24][CH2:25][CH2:26][Si:27]([CH3:30])([CH3:29])[CH3:28])[C:9]2=[N:10][CH:11]=1

Participants

5

Reactant 3

HCID 14496CyclobutanoneHCID 67002903HCID 67002903, compoundHCID 178418339Butyllithium

Product 1

HCID 670038311-(1-(5-chloro-2-(1-methyl-1H-pyrazol-4-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl)-1H-pyrazol-4-yl)cyclobutanol

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A −78° C. solution of Example 113F (75 mgs, 0.148 mmol) in tetrahydrofuran (2.1 mL) was treated with n-butyllithium (2.45 M in hexanes, 0.121 mL, 0.295 mmol) dropwise over 3 minutes, and the reaction was stirred for 2 minutes. Cyclobutanone (0.022 mL, 0.295 mmol) was added, and the reaction was stirred for 1 hour at −78° C. The reaction was quenched by the addition of saturated aqueous ammonium chloride. The mixture was extracted with ethyl acetate. The organic layer was washed with brine, dried over anhydrous sodium sulfate, filtered, and concentrated under reduced pressure. The concentrate was purified by flash chromatography on a silica gel column, eluting with a gradient of 0% to 4% methanol in dichloromethane, to provide the title compound. MS ESI(+) m/z 499.2 [M+H]+.

Workup

  1. stirringthe reaction was stirred for 1 hour at −78° C
  2. customThe reaction was quenched by the addition of saturated aqueous ammonium chloride
  3. extractionThe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed with brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated under reduced pressure
  8. customThe concentrate was purified by flash chromatography on a silica gel column
  9. washeluting with a gradient of 0% to 4% methanol in dichloromethane

Sources & evidence

ORD record
ord-513b6a7664834835b99d33a7d0eaf75b
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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