Iodoacetamide → N-{3-[(1-(2-amino-2-oxoethyl)-6-{[(4-methylphenyl)sulfonyl]imino}-1,6-dihydropyridin-3-yl)oxy]phenyl}-3-(1-cyano-1-methylethyl)benzamide

HRID 1874569Notes

Reaction equation

HRID 1874569 reaction equation
[C:1]([C:3]([C:6]1[CH:7]=[C:8]([CH:36]=[CH:37][CH:38]=1)[C:9]([NH:11][C:12]1[CH:17]=[CH:16][CH:15]=[C:14]([O:18][C:19]2[CH:20]=[N:21][C:22]([NH:25][S:26]([C:29]3[CH:34]=[CH:33][C:32]([CH3:35])=[CH:31][CH:30]=3)(=[O:28])=[O:27])=[CH:23][CH:24]=2)[CH:13]=1)=[O:10])([CH3:5])[CH3:4])#[N:2].C(N(CC)C(C)C)(C)C.I[CH2:49][C:50]([NH2:52])=[O:51]>CN(C)C=O>[NH2:52][C:50](=[O:51])[CH2:49][N:21]1[C:22](=[N:25][S:26]([C:29]2[CH:30]=[CH:31][C:32]([CH3:35])=[CH:33][CH:34]=2)(=[O:27])=[O:28])[CH:23]=[CH:24][C:19]([O:18][C:14]2[CH:13]=[C:12]([NH:11][C:9](=[O:10])[C:8]3[CH:36]=[CH:37][CH:38]=[C:6]([C:3]([C:1]#[N:2])([CH3:5])[CH3:4])[CH:7]=3)[CH:17]=[CH:16][CH:15]=2)=[CH:20]1

Participants

5

Reactant 3

HCID 3727IodoacetamideHCID 81531DiisopropylethylamineHCID 573878173-(1-cyano-1-methylethyl)-N-{3-[(6-{[(4-methylphenyl)sulfonyl]amino}pyridin-3-yl)oxy]phenyl}benzamide

Product 1

HCID 68417870N-{3-[(1-(2-amino-2-oxoethyl)-6-{[(4-methylphenyl)sulfonyl]imino}-1,6-dihydropyridin-3-yl)oxy]phenyl}-3-(1-cyano-1-methylethyl)benzamideYield 63%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of 3-(1-cyano-1-methylethyl)-N-{3-[(6-{[(4-methylphenyl)sulfonyl]amino}pyridin-3-yl)oxy]phenyl}benzamide (3.2 g, 6.08 mmol) in N,N-dimethylformamide (20 mL) was added N,N-diisopropylethylamine (1.11 mL, 6.38 mmol), and the mixture was stirred at room temperature for 15 min. 2-Iodoacetamide (1.18 g, 6.38 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature for 48 hr. The reaction mixture was concentrated under reduced pressure, 5% aqueous sodium hydrogen carbonate solution (150 mL) was added to the residue, and the mixture was extracted with ethyl acetate (300 mL). The organic layer was washed with saturated brine (150 mL), and dried over anhydrous sodium sulfate. The insoluble material was removed by filtration, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=50/50→0/100), and triturated with ethyl acetate, diisopropyl ether and hexane to give the title compound (2.23 g, 63%) as a colorless solid.

Workup

  1. stirringthe mixture was stirred at room temperature for 48 hr
  2. concentrationThe reaction mixture was concentrated under reduced pressure, 5% aqueous sodium hydrogen carbonate solution (150 mL)
  3. additionwas added to the residue
  4. extractionthe mixture was extracted with ethyl acetate (300 mL)
  5. washThe organic layer was washed with saturated brine (150 mL)
  6. dry with materialdried over anhydrous sodium sulfate
  7. customThe insoluble material was removed by filtration
  8. concentrationthe filtrate was concentrated under reduced pressure
  9. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=50/50→0/100)
  10. customtriturated with ethyl acetate, diisopropyl ether and hexane

Sources & evidence

ORD record
ord-c62c0c52e6b44fd69893c939a7174d93
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Reaction notes

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