Cesium carbonate → 5-(4-(6-(4-(2,2-Dimethyl-1,3-dioxan-5-yl)phenoxy)-5-methylpyrimidin-4-yloxy)piperidin-1-yl)-3-isopropyl-1,2,4-oxadiazole

HRID 1619441

Reaction equation

HRID 1619441 reaction equation
C(=O)([O-])[O-].[Cs+].[Cs+].Cl[C:8]1[N:13]=[CH:12][N:11]=[C:10]([O:14][CH:15]2[CH2:20][CH2:19][N:18]([C:21]3[O:25][N:24]=[C:23]([CH:26]([CH3:28])[CH3:27])[N:22]=3)[CH2:17][CH2:16]2)[C:9]=1[CH3:29].[CH3:30][C:31]1([CH3:44])[O:36][CH2:35][CH:34]([C:37]2[CH:42]=[CH:41][C:40]([OH:43])=[CH:39][CH:38]=2)[CH2:33][O:32]1>CN(C=O)C>[CH3:30][C:31]1([CH3:44])[O:32][CH2:33][CH:34]([C:37]2[CH:42]=[CH:41][C:40]([O:43][C:8]3[N:13]=[CH:12][N:11]=[C:10]([O:14][CH:15]4[CH2:20][CH2:19][N:18]([C:21]5[O:25][N:24]=[C:23]([CH:26]([CH3:28])[CH3:27])[N:22]=5)[CH2:17][CH2:16]4)[C:9]=3[CH3:29])=[CH:39][CH:38]=2)[CH2:35][O:36]1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 675102564-(2,2-Dimethyl-1,3-dioxan-5-yl)phenolHCID 865973665-(4-(6-Chloro-5-methylpyrimidin-4-yloxy)piperidin-1-yl)-3-isopropyl-1,2,4-oxadiazole

Product 1

HCID 675159055-(4-(6-(4-(2,2-Dimethyl-1,3-dioxan-5-yl)phenoxy)-5-methylpyrimidin-4-yloxy)piperidin-1-yl)-3-isopropyl-1,2,4-oxadiazoleYield 44.9%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

Cesium carbonate (755 mg, 0.002317 moles) was added to a solution of 5-(4-(6-chloro-5-methylpyrimidin-4-yloxy)piperidin-1-yl)-3-isopropyl-1,2,4-oxadiazole (1.2 gm, 0.003365 moles) and 4-(2,2-dimethyl-1,3-dioxan-5-yl)phenol (700 mg, 0.003365 moles) in dry DMF (10 ml) and the reaction mixture was stirred at 80° C. for 3 hours. Then reaction mixture was poured into ice cold water and extracted with ethyl acetate. The organic extract was successively washed with water & brine, dried over sodium sulfate and concentrated under reduced pressure. The crude product so obtained was purified by column chromatography (silica gel) using 15% ethyl acetate in hexane as eluent to obtain 770 mg product as white solid.

Workup

  1. customThen reaction mixture
  2. additionwas poured into ice cold water
  3. extractionextracted with ethyl acetate
  4. extractionThe organic extract
  5. washwas successively washed with water & brine
  6. dry with materialdried over sodium sulfate
  7. concentrationconcentrated under reduced pressure
  8. customThe crude product so obtained
  9. customwas purified by column chromatography (silica gel)

Sources & evidence

ORD record
ord-8547c1dc5c5647e9843dc3f5e033f4f9
Source dataset
uspto-grants-2014_07
Patent number
US08772302B2

Linked notes

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