Hydrochloric Acid → N-Benzyl-2-cyclohexyl-2-[5,6-difluoro-2-((S)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-acetamide

HRID 1099465Notes

Reaction equation

HRID 1099465 reaction equation
[NH2:1][C:2]1[CH:7]=[C:6]([F:8])[C:5]([F:9])=[CH:4][C:3]=1[NH:10][C:11](=O)O.CO[C@@H:16]([C:20]1[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=1)[C:17]([OH:19])=O.[CH:26]1([CH:32]=[O:33])[CH2:31][CH2:30][CH2:29][CH2:28][CH2:27]1.[CH2:34]([N+:41]#[C-])[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1.Cl.[CH3:44]O>O1CCOCC1>[CH2:34]([NH:41][C:17](=[O:19])[CH:16]([CH:20]1[CH2:21][CH2:22][CH2:23][CH2:24][CH2:25]1)[N:1]1[C:2]2[CH:7]=[C:6]([F:8])[C:5]([F:9])=[CH:4][C:3]=2[N:10]=[C:11]1[C@@H:32]([O:33][CH3:44])[C:26]1[CH:31]=[CH:30][CH:29]=[CH:28][CH:27]=1)[C:35]1[CH:40]=[CH:39][CH:38]=[CH:37][CH:36]=1

Participants

8

Reactant 6

HCID 313Hydrochloric AcidHCID 887MethanolHCID 16275CyclohexanecarboxaldehydeHCID 82558Benzyl isocyanideHCID 643325(+)-Methoxyphenylacetic acidHCID 86640864(2-Amino-4,5-difluoro-phenyl)-carbamic acid

Product 1

HCID 66810470N-Benzyl-2-cyclohexyl-2-[5,6-difluoro-2-((S)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-acetamide

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

To a mixture of (2-amino-4,5-difluoro-phenyl)-carbamic acid tent-butyl ester (1.00 g, 4 mmol, 1.0 equiv) and (S)-alpha-methoxyphenylacetic acid (0.68 g, 1.0 equiv., [CAS RN 26164-26-1]) in methanol (25 mL) were added cyclohexanecarbaldehyde (0.459 g, 4 mmol, 1.0 equiv; [2043-61-0]) and benzyl isonitrile (0.48 g, 1.0 equiv., 4 mmol, CAS RN 10340-91-7). The mixture was stirred overnight at room temperature. A solution of 4 M HCl in dioxane (3 mL) was added, and the reaction mixture stirred at room temperature overnight. The mixture was partitioned between water (100 ml) and ethyl acetate (100 ml). The phases were separated and the aqueous phase extracted with ethyl acetate (2×50 ml), the combined organic phases washed with brine, dried over sodium sulfate and evaporated under reduced pressure to afford the title compound as an orange gum (2.16 g, quant., mixture of diastereomers) that was used without further purification. MS (ISP): 504.1 [M+H]+.

Workup

  1. stirringthe reaction mixture stirred at room temperature overnight
  2. customThe mixture was partitioned between water (100 ml) and ethyl acetate (100 ml)
  3. customThe phases were separated
  4. extractionthe aqueous phase extracted with ethyl acetate (2×50 ml)
  5. washthe combined organic phases washed with brine
  6. dry with materialdried over sodium sulfate
  7. customevaporated under reduced pressure

Sources & evidence

ORD record
ord-1ad4cdf1cb3a4225a0a011929abc171e
Source dataset
uspto-grants-2012_03
Patent number
US08143422B2

Reaction notes

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