Cesium carbonate → Ethyl (3S)-3-[4-[[2-(2,6-dimethylphenyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]methoxy]phenyl]hex-4-ynoate

HRID 2272839Notes

Reaction equation

HRID 2272839 reaction equation
[OH:1][C:2]1[CH:7]=[CH:6][C:5]([C@@H:8]([C:15]#[C:16][CH3:17])[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:4][CH:3]=1.C([O-])([O-])=O.[Cs+].[Cs+].Cl[CH2:25][C:26]1[CH:27]=[CH:28][C:29]2[N:30]([N:32]=[C:33]([C:35]3[C:40]([CH3:41])=[CH:39][CH:38]=[CH:37][C:36]=3[CH3:42])[N:34]=2)[CH:31]=1>CN(C=O)C>[CH3:41][C:40]1[CH:39]=[CH:38][CH:37]=[C:36]([CH3:42])[C:35]=1[C:33]1[N:34]=[C:29]2[CH:28]=[CH:27][C:26]([CH2:25][O:1][C:2]3[CH:3]=[CH:4][C:5]([C@@H:8]([C:15]#[C:16][CH3:17])[CH2:9][C:10]([O:12][CH2:13][CH3:14])=[O:11])=[CH:6][CH:7]=3)=[CH:31][N:30]2[N:32]=1

Participants

5

Reactant 3

HCID 10796Cesium carbonateHCID 67087065Ethyl (3S)-3-(4-hydroxyphenyl)hex-4-ynoateHCID 1181300036-(Chloromethyl)-2-(2,6-dimethylphenyl)-[1,2,4]triazolo[1,5-a]pyridine

Product 1

HCID 118151368Ethyl (3S)-3-[4-[[2-(2,6-dimethylphenyl)-[1,2,4]triazolo[1,5-a]pyridin-6-yl]methoxy]phenyl]hex-4-ynoateYield 69.7%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

To a solution of (S)-ethyl 3-(4-hydroxyphenyl)hex-4-ynoate (WO05/086661) (0.2 g, 0.87 mmol) in DMF (20 mL) is added Cs2CO3 (0.84 g, 2.59 mmol) and 6-(chloromethyl)-2-(2,6-dimethylphenyl)-[1,2,4]triazolo[1,5-a]pyridine (0.187 g, 0.69 mmol). The reaction mixture is stirred at room temperature for 16 hours. The reaction mixture is poured into ice cold water and extracted with EtOAc (3×50 mL). The combined organic extracts are washed with water (2×50 mL), brine (50 mL), dried over anhydrous Na2SO4, filtered, and evaporated to dryness. The crude material is purified by combiflash silica gel chromatography eluting with 13% EtOAc in hexane to give the title compound as colourless liquid (0.225 g, 55%). LCMS m/z 468 (M+H)+.

Workup

  1. additionThe reaction mixture is poured into ice cold water
  2. extractionextracted with EtOAc (3×50 mL)
  3. washThe combined organic extracts are washed with water (2×50 mL), brine (50 mL)
  4. dry with materialdried over anhydrous Na2SO4
  5. filtrationfiltered
  6. customevaporated to dryness
  7. customThe crude material is purified by combiflash silica gel chromatography
  8. washeluting with 13% EtOAc in hexane

Sources & evidence

ORD record
ord-536054ca43b04330b56fccc454f0faf8
Source dataset
uspto-grants-2015_09
Patent number
US09120793B2

Reaction notes

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