Hydrochloric Acid → N-benzyl-2-[2-(4-chloro-2-methyl-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-acetamide

HRID 417135

Reaction equation

HRID 417135 reaction equation
[CH:1]1([CH:7]([N:19]2[C:23]3[CH:24]=[C:25]([F:29])[C:26]([F:28])=[CH:27][C:22]=3[N:21]=C2C2C(OC)=NC(OC)=CC=2)[CH2:8][O:9]C2C=CC(C(O)=O)=CN=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:40][C:41]1[CH:49]=[CH:48][C:44]([C:45](O)=O)=[C:43]([CH3:50])[CH:42]=1.C1(C=O)CCCCC=1.[CH2:59]([N+:66]#[C-])[C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1.Cl>CO.O1CCOCC1>[CH2:59]([NH:66][C:8](=[O:9])[CH:7]([N:19]1[C:23]2[CH:24]=[C:25]([F:29])[C:26]([F:28])=[CH:27][C:22]=2[N:21]=[C:45]1[C:44]1[CH:48]=[CH:49][C:41]([Cl:40])=[CH:42][C:43]=1[CH3:50])[CH:1]1[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1)[C:60]1[CH:65]=[CH:64][CH:63]=[CH:62][CH:61]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 82558Benzyl isocyanideHCID 3482694-Chloro-2-methylbenzoic acidHCID 51845401-Cyclohexene-1-carboxaldehydeHCID 461857196-{2-Cyclohexyl-2-[2-(2,6-dimethoxy-pyridin-3-yl)-5,6-difluoro-benzoimidazol-1-yl]-ethoxy}-nicotinic acid2×

Product 1

HCID 66619232N-benzyl-2-[2-(4-chloro-2-methyl-phenyl)-5,6-difluoro-benzoimidazol-1-yl]-2-cyclohexyl-acetamide

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Procedure

To the solution of 1.5 g (6.145 mmol) 2-amino-4,5-difluoro-phenyl)-carbamic acid tert-butyl ester (Example 73, intermediate g), 1.080 g (6.145 mmol) 4-chloro-2-methyl-benzoic acid (commercially available), 985.5 ul (7.375 mmol) cyclohexenecarbaldehyde (commercially available) and 763.5 ul (6.145 mmol) benzyl isocyanide (commercially available) were dissolved in 15 ml methanol and the light brown solution was stirred at room temperature overnight. Then 15.00 ml (60.0 mmol) 4M hydrochloric acid in dioxane (commercially available) were added and the reaction mixture was stirred at room temperature for 4.5 h and then evaporated. The residue was taken up in ethyl acetate and aqueous saturated sodium bicarbonate solution, the phases were separated, the organic phase extracted a second time with ethyl acetate and the combined organic layers washed with water and brine to give, after evaporation, the compound as yellow foam which was pure enough for the next step without further purification. MS (ESI): m/z=508.02 (M+).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 4.5 h
  2. customevaporated
  3. customaqueous saturated sodium bicarbonate solution, the phases were separated
  4. extractionthe organic phase extracted a second time with ethyl acetate
  5. washthe combined organic layers washed with water and brine
  6. customto give
  7. customafter evaporation
  8. customthe compound as yellow foam which was pure enough for the next step without further purification

Sources & evidence

ORD record
ord-6b1d4455da4c49a898f401621b4a2579
Source dataset
uspto-grants-2012_01
Patent number
US08088930B2

Linked notes

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