Dimethylformamide → 4-(4-bromo-1H-pyrazol-1-yl)-1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridine

HRID 1962725Notes

Reaction equation

HRID 1962725 reaction equation
[Br:1][C:2]1[CH:3]=[N:4][N:5]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[NH:13][CH:14]=[CH:15][C:8]=23)[CH:6]=1.CN(C)C=O.[H-].[Na+].[CH3:23][Si:24]([CH3:31])([CH3:30])[CH2:25][CH2:26][O:27][CH2:28]Cl>>[Br:1][C:2]1[CH:3]=[N:4][N:5]([C:7]2[CH:12]=[CH:11][N:10]=[C:9]3[N:13]([CH2:28][O:27][CH2:26][CH2:25][Si:24]([CH3:31])([CH3:30])[CH3:23])[CH:14]=[CH:15][C:8]=23)[CH:6]=1

Participants

5

Reactant 4

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 27242712-Chloromethyl 2-(trimethylsilyl)ethyl etherHCID 574776724-(4-bromo-1H-pyrazol-1-yl)-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 574776734-(4-bromo-1H-pyrazol-1-yl)-1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridine

Conditions

Temperature
0 °C

Procedure

A solution of 4-(4-bromo-1H-pyrazol-1-yl)-1H-pyrrolo[2,3-b]pyridine (1.1 g, 0.0042 mol) in N,N-dimethylformamide (20.0 mL, 0.258 mol) was cooled to 0° C. Sodium hydride (160.0 mg, 0.006667 mol) (60% in oil) was added and the mixture stirred for 10 min. [β-(Trimethylsilyl)ethoxy]methyl chloride (1.4 mL, 0.0079 mol) was added and stirred for 20 min at 0° C. The reaction was partitioned between ethyl acetate and water. The organic layer was washed with brine, dried over MgSO4 and concentrated to give the crude material. The product was purified by FCC on silica gel (EtOAc/Hexanes, 1/10) to give 4-(4-bromo-1H-pyrazol-1-yl)-1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridine as a solid product, LC/MS (M+H)+: 393, 395, 1H NMR (CDCl3) δ 8.47 (d, 1H, J=7.0), 8.27 (s, 1H), 7.88 (s, 1H), 7.52 (d, 1H, J=4.5), 7.39 (d, 1H, J=7.0), 7.069 (d, 1H, J=4.5), 5.80 (s, 2H), 3.6 (t, 2H), 1.95 (t, 2H), 0.0 (s, 9H).

Workup

  1. additionwas added
  2. customThe reaction was partitioned between ethyl acetate and water
  3. washThe organic layer was washed with brine
  4. dry with materialdried over MgSO4
  5. concentrationconcentrated
  6. customto give the crude material
  7. customThe product was purified by FCC on silica gel (EtOAc/Hexanes, 1/10)

Sources & evidence

ORD record
ord-dbcae6d05571483abd0d2b2ab68295ad
Source dataset
uspto-grants-2013_04
Patent number
US08415362B2

Reaction notes

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