Cesium carbonate → 2-[1-(1-benzhydryl-azetidin-3-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

HRID 246078Notes

Reaction equation

HRID 246078 reaction equation
[F:1][C:2]1[CH:10]=[C:9]2[C:5]([C:6]([C:11]3[N:12]=[C:13]4[C:19]([CH:20]=[O:21])=[CH:18][N:17]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:14]4=[N:15][CH:16]=3)=[N:7][NH:8]2)=[CH:4][CH:3]=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH:36]([N:49]1[CH2:52][CH:51](OS(C)(=O)=O)[CH2:50]1)([C:43]1[CH:48]=[CH:47][CH:46]=[CH:45][CH:44]=1)[C:37]1[CH:42]=[CH:41][CH:40]=[CH:39][CH:38]=1>CN(C=O)C>[CH:36]([N:49]1[CH2:52][CH:51]([N:8]2[C:9]3[C:5](=[CH:4][CH:3]=[C:2]([F:1])[CH:10]=3)[C:6]([C:11]3[N:12]=[C:13]4[C:19]([CH:20]=[O:21])=[CH:18][N:17]([CH2:22][O:23][CH2:24][CH2:25][Si:26]([CH3:29])([CH3:28])[CH3:27])[C:14]4=[N:15][CH:16]=3)=[N:7]2)[CH2:50]1)([C:43]1[CH:44]=[CH:45][CH:46]=[CH:47][CH:48]=1)[C:37]1[CH:38]=[CH:39][CH:40]=[CH:41][CH:42]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 27587161-(Diphenylmethyl)azetidin-3-yl methanesulfonateHCID 866779442-(6-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanylethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde

Product 1

HCID 866779452-[1-(1-benzhydryl-azetidin-3-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehydeYield 38.1%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
100 °C

Procedure

In a microwave vial 2-(6-fluoro-1H-indazol-3-yl)-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde (300 mg, 0.73 mmol) was dissolved in DMF (6 ml) and cesium carbonate (713 mg, 2.19 mmol) and methanesulfonic acid 1-benzhydryl-azetidin-3-yl ester (347 mg, 1.09 mmol) were added. The vial was sealed and heated in a microwave reactor at 100° C. 3 h. The reaction was cooled, quenched with water and extracted with EtOAc (2×). The combined organics were washed with water and brine then dried over MgSO4 and concentrated. The crude residue was purified by silica gel chromatography with 20% to 30% EtOAc/hexanes to provide 176 mg (38%) of 2-[1-(1-benzhydryl-azetidin-3-yl)-6-fluoro-1H-indazol-3-yl]-5-(2-trimethylsilanyl-ethoxymethyl)-5H-pyrrolo[2,3-b]pyrazine-7-carbaldehyde as an orange foam.

Workup

  1. customThe vial was sealed
  2. custom3 h
  3. temperatureThe reaction was cooled
  4. customquenched with water
  5. extractionextracted with EtOAc (2×)
  6. washThe combined organics were washed with water and brine
  7. dry with materialthen dried over MgSO4
  8. concentrationconcentrated
  9. customThe crude residue was purified by silica gel chromatography with 20% to 30% EtOAc/hexanes

Sources & evidence

ORD record
ord-1d2e91251a7740e6a34cfc20e44ce05e
Source dataset
uspto-grants-2014_02
Patent number
US08658646B2

Reaction notes

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