Dimethylformamide → 4-(2-tert-butyl-1H-imidazol-5-yl)-1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridine

HRID 1817530Notes

Reaction equation

HRID 1817530 reaction equation
Cl[CH2:2][C:3]([C:5]1[CH:10]=[CH:9][N:8]=[C:7]2[N:11]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[CH:12]=[CH:13][C:6]=12)=O.C[N:23]([CH:25]=O)C.[C:27]([O-])(=O)[C:28]([CH3:31])(C)[CH3:29].[Cs+].C([O-])(=O)C.[NH4+:39]>O>[C:28]([C:25]1[NH:23][C:3]([C:5]2[CH:10]=[CH:9][N:8]=[C:7]3[N:11]([CH2:14][O:15][CH2:16][CH2:17][Si:18]([CH3:21])([CH3:20])[CH3:19])[CH:12]=[CH:13][C:6]=23)=[CH:2][N:39]=1)([CH3:31])([CH3:29])[CH3:27]

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 517165Ammonium AcetateHCID 583616Cesium pivalateHCID 574775702-chloro-1-(1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)ethanone

Product 1

HCID 574775694-(2-tert-butyl-1H-imidazol-5-yl)-1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridineYield 52%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a solution of 2-chloro-1-(1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridin-4-yl)ethanone (prepared, e.g., as in Ex. 50, Step 1) (0.054 g, 0.00017 mol) in DMF (1.8 mL, 0.023 mol) was added cesium pivalate (0.0389 g, 0.000166 mol) and the reaction was stirred at room temperature for 16 hours. Ammonium acetate (0.45 g, 0.0058 mol) was added, and the reaction was heated in the microwave to 170° C. for 5 minutes. Water was added and the product was extracted with MTBE. The combined organic extracts were dried over sodium sulfate, then filtered and concentrated. The crude residue was purified by flash column chromatography (2.5% MeOH/DCM) to yield 4-(2-tert-butyl-1H-imidazol-5-yl)-1-[2-(trimethylsilyl)ethoxy]methyl-1H-pyrrolo[2,3-b]pyridine (32 mg, 52%). 1H NMR (400 MHz, CDCl3): δ 8.31 (d, 1H), 7.50 (s, 1H), 7.40 (d, 1H), 7.37 (d, 1H), 6.94 (d, 1H), 5.69 (s, 2H), 3.52 (dd, 2H), 1.46 (s, 9H), 0.90 (dd, 2H), −0.08 (s, 9H); MS(ES): 371 (M+1).

Workup

  1. temperaturethe reaction was heated in the microwave to 170° C. for 5 minutes
  2. extractionthe product was extracted with MTBE
  3. dry with materialThe combined organic extracts were dried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crude residue was purified by flash column chromatography (2.5% MeOH/DCM)

Sources & evidence

ORD record
ord-f424446a4ee8495db65d386bb5b44f58
Source dataset
uspto-grants-2009_10
Patent number
US07598257B2

Reaction notes

Loading…