Pyridine → 4-{2-Cyclohexyl-2-[5,6-difluoro-2-((S)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-acetylamino}-benzoic acid ethyl ester

HRID 1099467Notes

Reaction equation

HRID 1099467 reaction equation
[CH:1]1([CH:7]([N:11]2[C:15]3[CH:16]=[C:17]([F:21])[C:18]([F:20])=[CH:19][C:14]=3[N:13]=[C:12]2[C@@H:22]([O:29][CH3:30])[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)[C:8](O)=[O:9])[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.N1C=CC=CC=1.S(Cl)(Cl)=O.[NH2:41][C:42]1[CH:52]=[CH:51][C:45]([C:46]([O:48][CH2:49][CH3:50])=[O:47])=[CH:44][CH:43]=1>ClCCl>[CH2:49]([O:48][C:46](=[O:47])[C:45]1[CH:51]=[CH:52][C:42]([NH:41][C:8](=[O:9])[CH:7]([CH:1]2[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]2)[N:11]2[C:15]3[CH:16]=[C:17]([F:21])[C:18]([F:20])=[CH:19][C:14]=3[N:13]=[C:12]2[C@@H:22]([O:29][CH3:30])[C:23]2[CH:28]=[CH:27][CH:26]=[CH:25][CH:24]=2)=[CH:43][CH:44]=1)[CH3:50]

Participants

6

Reactant 4

HCID 1049Pyridine2×HCID 2337BenzocaineHCID 24386Thionyl ChlorideHCID 66810386Cyclohexyl-[5,6-difluoro-2-((S)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-acetic acid

Product 1

HCID 668104074-{2-Cyclohexyl-2-[5,6-difluoro-2-((S)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-acetylamino}-benzoic acid ethyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a solution of cyclohexyl-[5,6-difluoro-2-((S)-methoxy-phenyl-methyl)-benzoimidazol-1-yl]-acetic acid (160 mg, 0.39 mmol, 1.0 equiv.) in dichloromethane (2 ml) was added pyridine (0.046 ml, 1.5 equiv.). Thionyl chloride (0.034 ml, 1.2 eq) was added dropwise. The mixture was stirred 1 h at room temperature. A solution of ethyl 4-amino-benzoate (64 mg, 0.95 equiv., [CAS RN 94-09-7]) and pyridine (0.031 ml, 1.1 equiv.) in dichloromethane (2 ml) was added and the mixture stirred overnight at room temperature. The mixture was applied to a 5 g silica gel column (Biotage) and the product eluted with EtOAc to afford the title compound as an orange solid that was used without further purification. MS (ISP): 562.3 [M+H]+.

Workup

  1. stirringthe mixture stirred overnight at room temperature
  2. washthe product eluted with EtOAc

Sources & evidence

ORD record
ord-f8ebb8828faa45a0b8fdc82b9ad52616
Source dataset
uspto-grants-2012_03
Patent number
US08143422B2

Reaction notes

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