N-Methyl-N-nitrosourea → 4-chloro-N-[(4-chloro-3-{[3-cyano-5-(cyclopropylmethyl)phenyl]oxy}-2-fluorophenyl)methyl]-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide

HRID 1874926Notes

Reaction equation

HRID 1874926 reaction equation
[OH-].[K+].[CH3:3]N(N=O)C(N)=O.[Cl:10][C:11]1[N:12]=[CH:13][N:14]([CH2:40][O:41][CH2:42][CH2:43][Si:44]([CH3:47])([CH3:46])[CH3:45])[C:15]=1[C:16]([NH:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([O:27][C:28]2[CH:33]=[C:32]([CH2:34][CH:35]=[CH2:36])[CH:31]=[C:30]([C:37]#[N:38])[CH:29]=2)[C:21]=1[F:39])=[O:17]>C(OCC)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:10][C:11]1[N:12]=[CH:13][N:14]([CH2:40][O:41][CH2:42][CH2:43][Si:44]([CH3:47])([CH3:46])[CH3:45])[C:15]=1[C:16]([NH:18][CH2:19][C:20]1[CH:25]=[CH:24][C:23]([Cl:26])=[C:22]([O:27][C:28]2[CH:33]=[C:32]([CH2:34][CH:35]3[CH2:3][CH2:36]3)[CH:31]=[C:30]([C:37]#[N:38])[CH:29]=2)[C:21]=1[F:39])=[O:17]

Participants

6

Reactant 3

HCID 12699N-Methyl-N-nitrosoureaHCID 14797Potassium HydroxideHCID 684834184-chloro-N-[(4-chloro-3-{[3-cyano-5-(2-propen-1-yl)phenyl]oxy}-2-fluorophenyl)methyl]-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide

Product 1

HCID 684866314-chloro-N-[(4-chloro-3-{[3-cyano-5-(cyclopropylmethyl)phenyl]oxy}-2-fluorophenyl)methyl]-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 3283Diethyl EtherSolvent2×

Conditions

Temperature
0 °C

Procedure

To a mixture of 30% aqueous KOH (11 mL) and diethyl ether (11 mL) was added N-methyl-N-nitrosourea (0.097 g, 0.938 mmol) in one portion with stirring and cooling at 0° C. and the reaction mixture was maintained at this temperature for 20 min. The organic phase was isolated, dried over KOH pellets and added dropwise to a solution of 4-chloro-N-[(4-chloro-3-{[3-cyano-5-(2-propen-1-yl)phenyl]oxy}-2-fluorophenyl)methyl]-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-imidazole-5-carboxamide (0.054 g, 0.094 mmol) and palladium(II) acetate (2.106 mg, 9.38 μmol) in diethyl ether (11.00 mL) with stirring and cooling at 0° C. The reaction mixture was stirred at 0° C. for 1 h and then allowed to warm to room temperature and stirred overnight at which time LC-MS indicated complete conversion to desired product.

Workup

  1. temperaturethe reaction mixture was maintained at this temperature for 20 min
  2. customThe organic phase was isolated
  3. dry with materialdried over KOH pellets
  4. stirringwith stirring
  5. temperaturecooling at 0° C
  6. stirringThe reaction mixture was stirred at 0° C. for 1 h
  7. temperatureto warm to room temperature
  8. stirringstirred overnight at which time LC-MS

Sources & evidence

ORD record
ord-0f6aa9817c744024ad68568792403f00
Source dataset
uspto-grants-2012_11
Patent number
US08304419B2

Reaction notes

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