Diethyl (cyanomethyl)phosphonate → 4-chloro-N-{[4-chloro-3-({3-chloro-5-[(E)-2-cyanoethenyl]phenyl}oxy)-2-fluorophenyl]methyl}-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide

HRID 1875156Notes

Reaction equation

HRID 1875156 reaction equation
[C:1]([CH2:3]P(=O)(OCC)OCC)#[N:2].CC(C)([O-])C.[K+].[Cl:18][C:19]1[N:20]=[CH:21][N:22]([CH2:46][O:47][CH2:48][CH2:49][Si:50]([CH3:53])([CH3:52])[CH3:51])[C:23]=1[C:24]([NH:26][CH2:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([O:35][C:36]2[CH:41]=[C:40]([CH:42]=O)[CH:39]=[C:38]([Cl:44])[CH:37]=2)[C:29]=1[F:45])=[O:25]>C1COCC1.CCOC(C)=O>[Cl:18][C:19]1[N:20]=[CH:21][N:22]([CH2:46][O:47][CH2:48][CH2:49][Si:50]([CH3:53])([CH3:52])[CH3:51])[C:23]=1[C:24]([NH:26][CH2:27][C:28]1[CH:33]=[CH:32][C:31]([Cl:34])=[C:30]([O:35][C:36]2[CH:41]=[C:40](/[CH:42]=[CH:3]/[C:1]#[N:2])[CH:39]=[C:38]([Cl:44])[CH:37]=2)[C:29]=1[F:45])=[O:25]

Participants

6

Reactant 3

HCID 75676Diethyl (cyanomethyl)phosphonateHCID 23665647Potassium tert-butoxideHCID 866449404-chloro-N-({4-chloro-3-[(3-chloro-5-formylphenyl)oxy]-2-fluorophenyl}methyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide

Product 1

HCID 684855794-chloro-N-{[4-chloro-3-({3-chloro-5-[(E)-2-cyanoethenyl]phenyl}oxy)-2-fluorophenyl]methyl}-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamideYield 66%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
0 °C

Procedure

To a solution of diethyl cyanomethylphosphonate (56.1 mg, 0.317 mmol) in THF (5 mL) at 0° C. was added potassium t-butoxide (1.0 M solution in THF) (0.317 ml, 0.317 mmol) and the mixture was stirred at 0° C. for 30 minutes. Next, 4-chloro-N-({4-chloro-3-[(3-chloro-5-formylphenyl)oxy]-2-fluorophenyl}methyl)-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide (165 mg, 0.288 mmol) was added and the reaction mixture was stirred at room temperature for 2 hours. The mixture was diluted with EtOAc and washed with water. The solvent was removed and the crude material was purified via silica gel chromatography to give 4-chloro-N-{[4-chloro-3-({3-chloro-5-[(E)-2-cyanoethenyl]phenyl}oxy)-2-fluorophenyl]methyl}-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide (113 mg, 0.190 mmol, 66% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 8.74 (t, 1H), 7.95 (s, 1H), 7.54 (d, 2H), 7.41-7.48 (m, 1H), 7.36 (t, 1H), 7.23 (s, 1H), 6.97 (s, 1H), 6.58 (d, 1H), 5.47 (s, 2H), 4.45 (d, 2H), 3.36 (t, 2H), 0.72 (t, 2H), −0.12 (s, 9H).

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 2 hours
  2. washwashed with water
  3. customThe solvent was removed
  4. customthe crude material was purified via silica gel chromatography

Sources & evidence

ORD record
ord-8b56fea79cdd429ea13f304bbd265967
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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