Water → 2-(4-{[4-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carbonyl]-amino}-3-cyclohex-1-enyl-phenyl)-2-methyl-propionic acid methyl ester

HRID 1190108Notes

Reaction equation

HRID 1190108 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[N:12]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:13]=[C:14]([C:16]#[N:17])[N:15]=2)=[O:10])=[C:4]([C:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]=2)[CH:3]=1.[CH3:32][O:33][C:34]([O:38][Si](C)(C)C)=[C:35]([CH3:37])[CH3:36].O>CN(C=O)C.CC(P(C(C)(C)C)C(C)(C)C)(C)C.CC(P(C(C)(C)C)C(C)(C)C)(C)C.[Pd].[F-].[F-].[Zn+2]>[CH3:32][O:33][C:34](=[O:38])[C:35]([C:2]1[CH:7]=[CH:6][C:5]([NH:8][C:9]([C:11]2[N:12]([CH2:18][O:19][CH2:20][CH2:21][Si:22]([CH3:25])([CH3:24])[CH3:23])[CH:13]=[C:14]([C:16]#[N:17])[N:15]=2)=[O:10])=[C:4]([C:26]2[CH2:31][CH2:30][CH2:29][CH2:28][CH:27]=2)[CH:3]=1)([CH3:37])[CH3:36]

Participants

7

Reactant 3

HCID 962WaterHCID 552336Silane, ((1-methoxy-2-methyl-1-propenyl)oxy)trimethyl-HCID 594575324-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid (4-bromo-2-cyclohex-1-enyl-phenyl)-amide

Product 1

HCID 589945082-(4-{[4-Cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carbonyl]-amino}-3-cyclohex-1-enyl-phenyl)-2-methyl-propionic acid methyl esterYield 46%

Reagents, catalysts & solvents 3

HCID 2734558Bis(tri-tert-butylphosphine)palladium(0)CatalystHCID 10129912Zinc(II) fluorideCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-cyano-1-(2-trimethylsilanyl-ethoxymethyl)-1H-imidazole-2-carboxylic acid (4-bromo-2-cyclohex-1-enyl-phenyl)-amide (as prepared in Example 1, step (f), 100 mg, 0.200 mmol), (1-methoxy-2-methyl-propenyloxy)-trimethyl-silane (61 μL, 0.30 mmol), Pd(t-Bu3P)2 (10.2 mg, 0.0200 mmol) and ZnF2 (10.3 mg, 0.100 mmol) in 2 mL of DMF was stirred at 80° C. for 2 d under Ar. After cooling to RT, the mixture was treated with H2O (20 mL) and extracted with EtOAc (2×20 mL). The combined organic layers were washed with H2O (10 mL) and brine (10 mL). After drying over Na2SO4 and concentrating in vacuo, the residue was purified by silica gel chromatography (DCM) to afford the title compound (48 mg, 46%) as a colorless oil. LC-MS (ESI, m/z): Calcd. for C28H38N4O4Si, 523.3 (M+H). found 523.0.

Workup

  1. temperatureAfter cooling to RT
  2. extractionextracted with EtOAc (2×20 mL)
  3. washThe combined organic layers were washed with H2O (10 mL) and brine (10 mL)
  4. dry with materialAfter drying over Na2SO4
  5. concentrationconcentrating in vacuo
  6. customthe residue was purified by silica gel chromatography (DCM)

Sources & evidence

ORD record
ord-4c07eaf2086644118176966379b2992c
Source dataset
uspto-grants-2014_03
Patent number
US08674100B2

Reaction notes

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