Water → 4-benzyloxy-3-[(4-(N-methyl-N-(1-ethoxycarbonyl-1-methylethyl)amino)-6-(3-(1-methylimidazolin-2-yl)phenoxy)-3,5-difluoropyridin-2-yl)oxy]benzonitrile

HRID 1066192Notes

Reaction equation

HRID 1066192 reaction equation
[CH2:1]([O:8][C:9]1[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][C:10]=1[O:17][C:18]1[C:23]([F:24])=[C:22]([N:25]([CH3:34])[C:26]([C:29]([O:31][CH2:32][CH3:33])=[O:30])([CH3:28])[CH3:27])[C:21]([F:35])=[C:20](F)[N:19]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[CH3:37][N:38]1[CH2:42][CH2:41][N:40]=[C:39]1[C:43]1[CH:44]=[C:45]([OH:49])[CH:46]=[CH:47][CH:48]=1.C(=O)([O-])[O-].[Cs+].[Cs+].O>CS(C)=O.C(OCC)(=O)C>[CH2:1]([O:8][C:9]1[CH:16]=[CH:15][C:12]([C:13]#[N:14])=[CH:11][C:10]=1[O:17][C:18]1[C:23]([F:24])=[C:22]([N:25]([CH3:34])[C:26]([C:29]([O:31][CH2:32][CH3:33])=[O:30])([CH3:27])[CH3:28])[C:21]([F:35])=[C:20]([O:49][C:45]2[CH:46]=[CH:47][CH:48]=[C:43]([C:39]3[N:38]([CH3:37])[CH2:42][CH2:41][N:40]=3)[CH:44]=2)[N:19]=1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 10796Cesium carbonateHCID 114238803-(1-Methylimidazolin-2-yl)phenolHCID 211983374-benzyloxy-3-[(4-(N-methyl-N-(1-ethoxycarbonyl-1-methylethyl)amino)-3,5,6-trifluoropyridin-2-yl)oxy]benzonitrile

Product 1

HCID 154348774-benzyloxy-3-[(4-(N-methyl-N-(1-ethoxycarbonyl-1-methylethyl)amino)-6-(3-(1-methylimidazolin-2-yl)phenoxy)-3,5-difluoropyridin-2-yl)oxy]benzonitrile

Reagents, catalysts & solvents 2

HCID 679Dimethyl SulfoxideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-benzyloxy-3-[(4-(N-methyl-N-(1-ethoxycarbonyl-1-methylethyl)amino)-3,5,6-trifluoropyridin-2-yl)oxy]benzonitrile (2.4 g, 4.5 mmol) in DMSO (50 mL) was added 3-((1-methyl)imidazolin-2-yl)phenol (0.8 g, 4.5 mmol) and cesium carbonate (1.9 g, 5.8 mmol). The resultant mixture was stirred at 35° C. After 13 hours, the mixture was then cooled to ambient temperature and poured into 200 mL of water and 200 mL of ethyl acetate. The aqueous layer was separated and extracted with 100 mL of ethyl acetate. The combined organic extracts were washed with 0.5 M aqueous KOH solution (200 mL) then brine (200 mL), dried over MgSO4, filtered, and concentrated in vacuo to afford 4-benzyloxy-3-[(4-(N-methyl-N-(1-ethoxycarbonyl-1-methylethyl)amino)-6-(3-(1-methylimidazolin-2-yl)phenoxy)-3,5-difluoropyridin-2-yl)oxy]benzonitrile as a solid foam: NMR (CDCl3) 7.4-7.0 (m, 12), 5.0 (s, 2), 4.2 (q, 2), 3.9 (t, 2), 3.5 (t, 2), 3.1 (s, 3), 2.8 (s, 3), 1.6 (s, 6), 1.3 (t, 3) ppm.

Workup

  1. customThe aqueous layer was separated
  2. extractionextracted with 100 mL of ethyl acetate
  3. washThe combined organic extracts were washed with 0.5 M aqueous KOH solution (200 mL)
  4. dry with materialbrine (200 mL), dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-e18f2d0c94104743b1f561d658b75037
Source dataset
uspto-grants-2001_06
Patent number
US06242454B1

Reaction notes

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