Cesium carbonate → 4-{4-[3-(6-Methylpyridin-2-yl)prop-2-yn-1-ylidene]piperidin-1-yl}isoquinoline

HRID 1895989Notes

Reaction equation

HRID 1895989 reaction equation
[CH3:1][C:2]1[CH:7]=[CH:6][CH:5]=[C:4]([C:8]#[C:9][CH:10]=[C:11]2[CH2:16][CH2:15][NH:14][CH2:13][CH2:12]2)[N:3]=1.Br[C:18]1[C:27]2[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=2)[CH:21]=[N:20][CH:19]=1.C(=O)([O-])[O-].[Cs+].[Cs+].C1(P(C2C=CC=CC=2)C2C=CC3C(=CC=CC=3)C=2C2C3C(=CC=CC=3)C=CC=2P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[CH3:1][C:2]1[N:3]=[C:4]([C:8]#[C:9][CH:10]=[C:11]2[CH2:12][CH2:13][N:14]([C:18]3[C:27]4[C:22](=[CH:23][CH:24]=[CH:25][CH:26]=4)[CH:21]=[N:20][CH:19]=3)[CH2:15][CH2:16]2)[CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 10796Cesium carbonateHCID 737434-BromoisoquinolineHCID 634876Binap, (A+-)-HCID 875504022-Methyl-6-(3-piperidin-4-ylideneprop-1-ynyl)pyridine

Product 1

HCID 875511624-{4-[3-(6-Methylpyridin-2-yl)prop-2-yn-1-ylidene]piperidin-1-yl}isoquinolineYield 59.9%

Reagents, catalysts & solvents 1

HCID 167845palladium(II) acetateCatalyst

Procedure

A mixture of the compound of Example 3 (0.076 g, 0.36 mmol), 4-bromoisoquinoline (0.064 g, 0.30 mmol), cesium carbonate (0.494 g, 1.5 mmol), 2,2′-bis(diphenylphosphino)-1,1′binaphthalene (0.011 g, 0.024 mmol), palladium(II)acetate (0.0027 mg, 0.012 mmol) in anhydrous and degassed toluene (3 mL) was heated at reflux under a nitrogen atmosphere for 18 h. The reaction mixture was cooled, poured into water and extracted with EtOAc. The combined organic layers were washed with brine, dried on Na2SO4 and evaporated to dryness in vacuo to afford a residue, which was purified by flash chromatography (CHCl3-1.4 N MeOH NH3 100:0.25) affording the title product (0.061 g).

Workup

  1. customdegassed toluene (3 mL)
  2. temperaturewas heated
  3. temperatureat reflux under a nitrogen atmosphere for 18 h
  4. temperatureThe reaction mixture was cooled
  5. additionpoured into water
  6. extractionextracted with EtOAc
  7. washThe combined organic layers were washed with brine
  8. customdried on Na2SO4
  9. customevaporated to dryness in vacuo
  10. customto afford a residue, which
  11. customwas purified by flash chromatography (CHCl3-1.4 N MeOH NH3 100:0.25)

Sources & evidence

ORD record
ord-e49706fabbd44f97a9d343b326ea7c0b
Source dataset
uspto-grants-2013_08
Patent number
US08518916B2

Reaction notes

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