Methyl iodide → HCID 66778146, compound

HRID 2090956Notes

Reaction equation

HRID 2090956 reaction equation
[CH:1]1([CH:7]([NH:23][C:24]2[CH:29]=[CH:28][C:27]([C:30]([N:32]([CH3:40])[CH2:33][CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])=[O:31])=[CH:26][CH:25]=2)[C:8]2[C:9]([CH2:21][CH3:22])=[N:10][N:11]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=3)[CH:12]=2)[CH2:6][CH2:5][CH2:4][CH2:3][CH2:2]1.[H-].[Na+].[CH3:43]I>CN(C)C(=O)C>[CH:1]1([CH:7]([N:23]([CH3:43])[C:24]2[CH:29]=[CH:28][C:27]([C:30]([N:32]([CH3:40])[CH2:33][CH2:34][C:35]([O:37][CH2:38][CH3:39])=[O:36])=[O:31])=[CH:26][CH:25]=2)[C:8]2[C:9]([CH2:21][CH3:22])=[N:10][N:11]([C:13]3[CH:18]=[CH:17][CH:16]=[C:15]([O:19][CH3:20])[CH:14]=3)[CH:12]=2)[CH2:2][CH2:3][CH2:4][CH2:5][CH2:6]1

Participants

5

Reactant 3

HCID 6328Methyl iodideHCID 24758Sodium hydrideHCID 66778826HCID 66778826, compound

Product 1

HCID 66778146HCID 66778146, compoundYield 75%

Reagents, catalysts & solvents 1

HCID 31374DimethylacetamideSolvent

Procedure

To a solution of ethyl 3-[{[4-({cyclohexyl[3-ethyl-1-(3-methoxyphenyl)-1H-pyrazol-4-yl]methyl}amino)phenyl]carbonyl}(methyl)amino]propanoate (1.1 g) synthesized in Example 78(4) in N,N-dimethylacetamide (5 mL) was added sodium hydride (0.16 g) under ice-cooling and, after stirring for 30 min, methyl iodide (0.37 mL) was added. The ice bath was removed, the reaction mixture was stirred at room temperature overnight, saturated aqueous ammonium chloride solution was added and the mixture was extracted with diethyl ether. The extract was washed with brine to give ethyl 3-[({4-[{cyclohexyl[3-ethyl-1-(3-methoxyphenyl)-1H-pyrazol-4-yl]methyl}(methyl)amino]phenyl}carbonyl)(methyl)amino]propanoate (0.23 g, 75%) as a pale-yellow oil. This was dissolved in ethanol (3.0 mL), 1N aqueous sodium hydroxide solution (1.5 mL) was added at room temperature, and the mixture was stirred at room temperature for 0.5 hr. Ethanol was evaporated under reduced pressure, 1N hydrochloric acid (1.5 mL) was added to the residue, and the mixture was extracted with ethyl acetate. The extract was washed with water, dried over magnesium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate:hexane=10:1, volume ratio) to give the title object compound (0.10 g, 10%) as a pale-yellow solid.

Workup

  1. temperaturecooling
  2. customThe ice bath was removed
  3. stirringthe reaction mixture was stirred at room temperature overnight
  4. additionsaturated aqueous ammonium chloride solution was added
  5. extractionthe mixture was extracted with diethyl ether
  6. washThe extract was washed with brine

Sources & evidence

ORD record
ord-56e92e51507f41e08b4b4c3db5570c4d
Source dataset
uspto-grants-2013_05
Patent number
US08436043B2

Reaction notes

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