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

HRID 1874536Notes

Reaction equation

HRID 1874536 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][C:12]2[N:17]=[CH:16][C:15]([O:18][C:19]3[CH:20]=[C:21]([NH:25][C:26](=[O:37])[C:27]4[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:36])([F:35])[F:34])[CH:28]=4)[CH:22]=[CH:23][CH:24]=3)=[CH:14][CH:13]=2)(=[O:10])=[O:9])=[CH:4][CH:3]=1.C(N(CC)C(C)C)(C)C.I[CH2:48][C:49]([NH2:51])=[O:50].O>CN(C)C=O>[NH2:51][C:49](=[O:50])[CH2:48][N:17]1[C:12](=[N:11][S:8]([C:5]2[CH:6]=[CH:7][C:2]([CH3:1])=[CH:3][CH:4]=2)(=[O:10])=[O:9])[CH:13]=[CH:14][C:15]([O:18][C:19]2[CH:20]=[C:21]([NH:25][C:26](=[O:37])[C:27]3[CH:32]=[CH:31][CH:30]=[C:29]([C:33]([F:35])([F:36])[F:34])[CH:28]=3)[CH:22]=[CH:23][CH:24]=2)=[CH:16]1

Participants

6

Reactant 4

HCID 962WaterHCID 3727IodoacetamideHCID 81531DiisopropylethylamineHCID 68418522N-{3-[(6-{[(4-methylphenyl)sulfonyl]amino}pyridin-3-yl)oxy]phenyl}-3-(trifluoromethyl)benzamide

Product 1

HCID 68416682N-{3-[(1-(2-amino-2-oxoethyl)-6-{[(4-methylphenyl)sulfonyl]imino}-1,6-dihydropyridin-3-yl)oxy]phenyl}-3-(trifluoromethyl)benzamideYield 61.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of N-{3-[(6-{[(4-methylphenyl)sulfonyl]amino}pyridin-3-yl)oxy]phenyl}-3-(trifluoromethyl)benzamide (2.7 g, 5.12 mmol) in N,N-dimethylformamide (18 mL) was added N,N-diisopropylethylamine (0.94 mL, 5.38 mmol), and the mixture was stirred at room temperature for 15 min. 2-Iodoacetamide (995 mg, 5.38 mmol) was added to the reaction mixture, and the mixture was stirred at room temperature for 18 hr. Water (200 mL) was added to the reaction mixture, and the mixture was extracted with ethyl acetate (300 mL). The organic layer was washed with water (100 mL) and saturated brine (100 mL), and dried over anhydrous sodium sulfate. The insoluble material was filtered off, and the filtrate was concentrated under reduced pressure. The obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=60/40→0/100) and recrystallized from ethyl acetate and hexane to give the title compound (1.84 g, 61%) as a colorless solid.

Workup

  1. stirringthe mixture was stirred at room temperature for 18 hr
  2. extractionthe mixture was extracted with ethyl acetate (300 mL)
  3. washThe organic layer was washed with water (100 mL) and saturated brine (100 mL)
  4. dry with materialdried over anhydrous sodium sulfate
  5. filtrationThe insoluble material was filtered off
  6. concentrationthe filtrate was concentrated under reduced pressure
  7. customThe obtained residue was purified by silica gel column chromatography (hexane/ethyl acetate=60/40→0/100)
  8. customrecrystallized from ethyl acetate and hexane

Sources & evidence

ORD record
ord-b5083a1c1764425c8fe9cdd6a60902ff
Source dataset
uspto-grants-2012_11
Patent number
US08304557B2

Reaction notes

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