Pyridine → 4-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [4-(2-tert-butylsulfamoyl-ethyl)-2-cyclohex-1-enyl-phenyl]-amide

HRID 1711291Notes

Reaction equation

HRID 1711291 reaction equation
[C:1]([C:3]1[N:4]=[C:5]([C:16]([OH:18])=O)[N:6]([CH2:8][O:9][CH2:10][CH2:11][Si:12]([CH3:15])([CH3:14])[CH3:13])[CH:7]=1)#[N:2].[K+].C(C1N=C(C([O-])=O)N(COCC[Si](C)(C)C)C=1)#N.N1C=CC=CC=1.O=S(Cl)Cl.[C:48]([NH:52][S:53]([CH2:56][CH2:57][C:58]1[CH:63]=[CH:62][C:61]([NH2:64])=[C:60]([C:65]2[CH2:70][CH2:69][CH2:68][CH2:67][CH:66]=2)[CH:59]=1)(=[O:55])=[O:54])([CH3:51])([CH3:50])[CH3:49]>C(Cl)Cl.O>[C:48]([NH:52][S:53]([CH2:56][CH2:57][C:58]1[CH:63]=[CH:62][C:61]([NH:64][C:16]([C:5]2[N:6]([CH2:8][O:9][CH2:10][CH2:11][Si:12]([CH3:13])([CH3:14])[CH3:15])[CH:7]=[C:3]([C:1]#[N:2])[N:4]=2)=[O:18])=[C:60]([C:65]2[CH2:70][CH2:69][CH2:68][CH2:67][CH:66]=2)[CH:59]=1)(=[O:54])=[O:55])([CH3:51])([CH3:49])[CH3:50]

Participants

8

Reactant 5

HCID 1049Pyridine2×HCID 24386Thionyl ChlorideHCID 587548162-(4-Amino-3-cyclohex-1-enyl-phenyl)-ethanesulfonic acid tert-butylamideHCID 591285854-Cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxylic acidHCID 67188357potassium 4-cyano-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-imidazole-2-carboxylate

Product 1

HCID 587548884-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid [4-(2-tert-butylsulfamoyl-ethyl)-2-cyclohex-1-enyl-phenyl]-amideYield 68%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid, potassium salt (as prepared in Example 11, step (d), 228 mg, 0.746 mmol) and pyridine (66 μL, 0.81 mmol) in DCM (5 mL), SOCl2 (60 μL, 0.81 mmol) was added at 0° C. The resulting mixture was stirred at RT for 1 h and transferred to a mixture of 2-(4-amino-3-cyclohex-1-enyl-phenyl)-ethanesulfonic acid tert-butylamide (as prepared in the previous step, 228 mg, 0.670 mg) and pyridine (66 μL, 0.81 mmol) in DCM (5 mL) at 0° C. The resulting mixture was stirred at RT over night. Water (20 mL) was then added and organic layer was separated, dried (Na2SO4) and concentrated. The residue obtained was purified on silica (20-50% EtOAc/hexane) to obtain the title compound (271 mg, 68%). Mass spectrum (ESI, m/z): Calcd. for C29H43N5O4SSi, 586.2 (M+H), found 586.0.

Workup

  1. additionwas added at 0° C
  2. stirringThe resulting mixture was stirred at RT over night
  3. customorganic layer was separated
  4. dry with materialdried (Na2SO4)
  5. concentrationconcentrated
  6. customThe residue obtained
  7. customwas purified on silica (20-50% EtOAc/hexane)

Sources & evidence

ORD record
ord-cd49251bc9c24bb4a17f5c99314a8553
Source dataset
uspto-grants-2010_09
Patent number
US07790724B2

Reaction notes

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