Sodium hydride → 4,5-dichloro-2-(1-methyl-1H-pyrazol-4-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine

HRID 2362718Notes

Reaction equation

HRID 2362718 reaction equation
[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][N:5]=[C:4]2[NH:9][C:10]([C:12]3[CH:13]=[N:14][N:15]([CH3:17])[CH:16]=3)=[CH:11][C:3]=12.[H-].[Na+].Cl[CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26]>CN(C)C=O>[Cl:1][C:2]1[C:7]([Cl:8])=[CH:6][N:5]=[C:4]2[N:9]([CH2:21][O:22][CH2:23][CH2:24][Si:25]([CH3:28])([CH3:27])[CH3:26])[C:10]([C:12]3[CH:13]=[N:14][N:15]([CH3:17])[CH:16]=3)=[CH:11][C:3]=12

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 67002816HCID 67002816, compound

Product 1

HCID 670037264,5-dichloro-2-(1-methyl-1H-pyrazol-4-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
-42 °C

Procedure

A solution of Example 113D (0.17 g, 0.636 mmol) in N,N-dimethylformamide (3.5 mL) was cooled to 0° C. in an ice bath, and sodium hydride (60% dispersion in mineral oil, 0.031 g, 0.776 mmol) was added. The reaction mixture was stirred 30 minutes, cooled to −42° C., and (2-(chloromethoxy)ethyl)trimethylsilane (0.146 mL, 0.827 mol) was added dropwise over 3 minutes. The reaction was stirred at −42° C. for 1 hour and was quenched with saturated aqueous ammonium chloride (3 mL). The mixture was partitioned between water and ethyl acetate. The organic layer was washed with water and 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 25% ethyl acetae in hexane, to provide the title compound. MS ESI(+) m/z 397.2 [M+H]+.

Workup

  1. stirringThe reaction was stirred at −42° C. for 1 hour
  2. customwas quenched with saturated aqueous ammonium chloride (3 mL)
  3. customThe mixture was partitioned between water and ethyl acetate
  4. washThe organic layer was washed with water and 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 25% ethyl acetae in hexane

Sources & evidence

ORD record
ord-d3af9c1b69524ceb82c8e561d00bb17c
Source dataset
uspto-grants-2014_04
Patent number
US08691810B2

Reaction notes

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