Sodium hydride → HCID 66995379, compound

HRID 2066430Notes

Reaction equation

HRID 2066430 reaction equation
[H-].[Na+].[Br:3][C:4]1[CH:12]=[C:11]2[C:7]([C:8]([C:21]3[CH:22]=[N:23][NH:24][CH:25]=3)=[N:9][N:10]2[CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:20])([CH3:19])[CH3:18])=[CH:6][CH:5]=1.Cl[CH2:27][CH2:28][N:29]1[CH2:33][CH2:32][CH2:31][CH2:30]1>CN(C=O)C>[Br:3][C:4]1[CH:12]=[C:11]2[C:7]([C:8]([C:21]3[CH:22]=[N:23][N:24]([CH2:27][CH2:28][N:29]4[CH2:33][CH2:32][CH2:31][CH2:30]4)[CH:25]=3)=[N:9][N:10]2[CH2:13][O:14][CH2:15][CH2:16][Si:17]([CH3:19])([CH3:20])[CH3:18])=[CH:6][CH:5]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 816691-(2-Chloroethyl)pyrrolidineHCID 136351078HCID 136351078, compound

Product 1

HCID 66995379HCID 66995379, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (17.46 mg, 0.437 mmol) was added in a single portion to a solution of 6-bromo-3-(1H-pyrazol-4-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-indazole (101 mg, 0.257 mmol) (prepared by substituting 4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole for 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole in Example 1C) in DMF (10 ml) at room temperature under argon. The resulting bubbling solution was stirred for 20 minutes, then treated with 1-(2-chloroethyl)pyrrolidine (51.5 mg, 0.385 mmol) which was dissolved in 0.5 ml DMF and added dropwise via pipette. The resulting mixture was stirred at 70° C. for 3 hours, allowed to cool, and partitioned between ethyl acetate and water. The organic extract was washed with brine, dried with MgSO4, and filtered. The filtrate was concentrated and the residue was purified via silica gel chromatography eluting with 3 to 5% CH2Cl2/CH3OH to give the title compound.

Workup

  1. customThe resulting bubbling solution
  2. additionadded dropwise via pipette
  3. stirringThe resulting mixture was stirred at 70° C. for 3 hours
  4. temperatureto cool
  5. custompartitioned between ethyl acetate and water
  6. extractionThe organic extract
  7. washwas washed with brine
  8. dry with materialdried with MgSO4
  9. filtrationfiltered
  10. concentrationThe filtrate was concentrated
  11. customthe residue was purified via silica gel chromatography
  12. washeluting with 3 to 5% CH2Cl2/CH3OH

Sources & evidence

ORD record
ord-1563e27cbc1e47c394d2506db3017ade
Source dataset
uspto-grants-2012_10
Patent number
US08293738B2

Reaction notes

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