Sodium hydride → N-(1-(1-(4-chlorophenyl)-1-(2-cyanocyclopropyl)propyl)-1H-indazol-4-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)methanesulfonamide

HRID 1427236Notes

Reaction equation

HRID 1427236 reaction equation
[H-].[Na+].[I-].[CH3:4][S+](C)(C)=O.[Cl:9][C:10]1[CH:15]=[CH:14][C:13]([C:16]([N:23]2[C:31]3[C:26](=[C:27]([N:32]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:43])[CH3:42])[S:33]([CH3:36])(=[O:35])=[O:34])[CH:28]=[CH:29][CH:30]=3)[CH:25]=[N:24]2)([CH2:21][CH3:22])/[CH:17]=[CH:18]/[C:19]#[N:20])=[CH:12][CH:11]=1>CS(C)=O>[Cl:9][C:10]1[CH:11]=[CH:12][C:13]([C:16]([N:23]2[C:31]3[C:26](=[C:27]([N:32]([CH2:37][O:38][CH2:39][CH2:40][Si:41]([CH3:44])([CH3:42])[CH3:43])[S:33]([CH3:36])(=[O:34])=[O:35])[CH:28]=[CH:29][CH:30]=3)[CH:25]=[N:24]2)([CH:17]2[CH2:4][CH:18]2[C:19]#[N:20])[CH2:21][CH3:22])=[CH:14][CH:15]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 74498Sulfoxonium, trimethyl-, iodide (1:1)HCID 86705042(E)-N-(1-(3-(4-chlorophenyl)-1-cyanopent-1-en-3-yl)-1H-indazol-4-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)methanesulfonamide

Product 1

HCID 70563960N-(1-(1-(4-chlorophenyl)-1-(2-cyanocyclopropyl)propyl)-1H-indazol-4-yl)-N-((2-(trimethylsilyl)ethoxy)methyl)methanesulfonamide

Reagents, catalysts & solvents 1

HCID 679Dimethyl SulfoxideSolvent2×

Procedure

A suspension of NaH (22 mg) in anhydrous DMSO (0.9 mL) was added trimethylsulfoxonium iodide (128 mg) at 0° C. and the mixture was stirred at rt for 3 h until the solution became clear. Then was added the solution of (E)-N-(1-(3-(4-chlorophenyl)-1-cyanopent-1-en-3-yl)-1H-indazol-4-yl)-N-((2-(trimethylsilyl)ethoxy)methyl) methanesulfonamide (42 mg) in anhydrous DMSO (0.1 mL) and the reaction mixture was stirred at 70° C. for 16 h. The solution was quenched with saturated NH4Cl solution, extracted with ethyl acetate (15 mL). The organic layer was washed with brine, dried over dry sodium sulfate, filtered and evaporated. The residue was purified by silica gel chromatography (PE/EA=4/1) to afford the title compound as a white solid. LC/MS m/z=559.2 [M+H]+.

Workup

  1. stirringthe reaction mixture was stirred at 70° C. for 16 h
  2. customThe solution was quenched with saturated NH4Cl solution
  3. extractionextracted with ethyl acetate (15 mL)
  4. washThe organic layer was washed with brine
  5. dry with materialdried over dry sodium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by silica gel chromatography (PE/EA=4/1)

Sources & evidence

ORD record
ord-02030e17748a4ac9a9a60c010a68c56f
Source dataset
uspto-grants-2015_01
Patent number
US08933113B2

Reaction notes

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