Sodium hydride → [3-(3-Chloro-pyrazin-2-YL)-azetidin-1-YL]-[1-(2,2,2-trifluoro-ethyl)-1H-benzoimidazol-2-YL]-methanone

HRID 1850289Notes

Reaction equation

HRID 1850289 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([N:12]1[CH2:15][CH:14]([C:16]2[C:21]([Cl:22])=[N:20][CH:19]=[CH:18][N:17]=2)[CH2:13]1)=[O:11].[H-].[Na+].[F:25][C:26]([F:30])([F:29])[CH2:27]I>CN(C=O)C>[Cl:22][C:21]1[C:16]([CH:14]2[CH2:13][N:12]([C:10]([C:2]3[N:3]([CH2:27][C:26]([F:30])([F:29])[F:25])[C:4]4[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=4[N:1]=3)=[O:11])[CH2:15]2)=[N:17][CH:18]=[CH:19][N:20]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 677091,1,1-Trifluoro-2-iodoethaneHCID 58546731(1H-benzoimidazol-2-yl)-[3-(3-chloro-pyrazin-2-yl)-azetidin-1-yl]-methanone

Product 1

HCID 58547172[3-(3-Chloro-pyrazin-2-YL)-azetidin-1-YL]-[1-(2,2,2-trifluoro-ethyl)-1H-benzoimidazol-2-YL]-methanoneYield 90%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (1H-benzoimidazol-2-yl)-[3-(3-chloro-pyrazin-2-yl)-azetidin-1-yl]-methanone (84), as prepared in Preparation 36 below, (314 mg, 1.0 mmol) in dry DMF (10 mL) was added sodium hydride (applied as 60% dispersion in oil, 62 mg, 1.5 mmol)) at 0° C. under N2 atmosphere. After 0.5 h, 1,1,1-Trifluoro-2-iodo-ethane (418 mg, 2.0 mmol) was added slowly. The reaction mixture was stirred at RT for 4 h. The reaction was quenched with water (10 mL) at 0° C. and extracted with EtOAc (3×20 mL). The combined organics were washed with water (2×15 mL), brine (20 mL), dried over sodium sulfate and filtered. The filtrate was concentrated and the residue was purified by flash column chromatography to provide (85) (355 mg, 0.90 mmol, 90% yield) as white solid.

Workup

  1. customThe reaction was quenched with water (10 mL) at 0° C.
  2. extractionextracted with EtOAc (3×20 mL)
  3. washThe combined organics were washed with water (2×15 mL), brine (20 mL)
  4. dry with materialdried over sodium sulfate
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated
  7. customthe residue was purified by flash column chromatography

Sources & evidence

ORD record
ord-384b07a5e64f4767b0c751266be16015
Source dataset
uspto-grants-2015_02
Patent number
US08957073B2

Reaction notes

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