Hydrochloric Acid → HCID 66619265, compound

HRID 417076Notes

Reaction equation

HRID 417076 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[N:12]([CH:13]([CH:16]3[CH2:21][CH2:20][CH2:19][CH2:18][CH2:17]3)[CH2:14][OH:15])[C:11]3[CH:22]=[C:23]([F:27])[C:24]([F:26])=[CH:25][C:10]=3[N:9]=2)=[CH:4][CH:3]=1.[H-].[Na+].[CH2:30]([O:32][C:33]([C:35]1[C:36]2[S:43][C:42](Cl)=[CH:41][C:37]=2[CH:38]=[N:39][CH:40]=1)=[O:34])[CH3:31].Cl>CN(C)C=O.C(OCC)(=O)C>[CH2:30]([O:32][C:33]([C:35]1[C:36]2[S:43][CH:42]=[CH:41][C:37]=2[C:38]([O:15][CH2:14][CH:13]([N:12]2[C:11]3[CH:22]=[C:23]([F:27])[C:24]([F:26])=[CH:25][C:10]=3[N:9]=[C:8]2[C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)[CH:16]2[CH2:17][CH2:18][CH2:19][CH2:20][CH2:21]2)=[N:39][CH:40]=1)=[O:34])[CH3:31]

Participants

7

Reactant 4

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 666193102-[2-(4-Chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-ethanolHCID 66619476HCID 66619476, compound

Product 1

HCID 66619265HCID 66619265, compoundYield 71%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To the solution of 0.2 g (0.51 mmol) 2-[2-(4-chloro-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-ethanol (Ex. 1, int. c) in 3 mL N,N-dimethylformamide, 27 mg (0.61 mmol) sodium hydride was added. After 15 min. 148 mg (0.61 mmol) chloro-thieno[3,2-c]pyridine-7-carboxylic acid ethyl ester was added and stirring was continued for another 2 h at room temperature. The reaction was poured on 20 mL 1N aqueous hydrochloric acid and 20 mL ethyl acetate. The phases were separated, the aqueous layers extracted with 20 mL ethyl acetate and the combined organic layers washed with 20 mL water and 20 mL brine, dried over magnesium sulfate, filtered and evaporated. The residue was purified by silica chromatography using a MPLC system (CombiFlash Companion, Isco Inc.) eluting with a gradient of n-heptane:ethyl acetate (100:0 to 75:25) to give the desired compound as a white solid (71%). MS (Turbo Spray): m/z=596.3 [M+H].

Workup

  1. waitwas continued for another 2 h at room temperature
  2. customThe phases were separated
  3. extractionthe aqueous layers extracted with 20 mL ethyl acetate
  4. washthe combined organic layers washed with 20 mL water and 20 mL brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. customevaporated
  8. customThe residue was purified by silica chromatography
  9. washeluting with a gradient of n-heptane:ethyl acetate (100:0 to 75:25)

Sources & evidence

ORD record
ord-fbe6b6ce69bf4037be586ab25777799d
Source dataset
uspto-grants-2012_01
Patent number
US08088930B2

Reaction notes

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