Cesium carbonate → 1-Methyl-5-(pyridin-4-yl)-3,4-dihydroisoquinoline

HRID 926242Notes

Reaction equation

HRID 926242 reaction equation
I[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH2:4][CH2:5][N:6]=[C:7]2[CH3:12].[N:13]1[CH:18]=[CH:17][C:16](B(O)O)=[CH:15][CH:14]=1.C([O-])([O-])=O.[Cs+].[Cs+]>O1CCOCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[CH3:12][C:7]1[C:8]2[C:3](=[C:2]([C:16]3[CH:17]=[CH:18][N:13]=[CH:14][CH:15]=3)[CH:11]=[CH:10][CH:9]=2)[CH2:4][CH2:5][N:6]=1

Participants

6

Reactant 3

HCID 10796Cesium carbonateHCID 2734379(Pyridin-4-yl)boronic acidHCID 867113155-Iodo-1-methyl-3,4-dihydroisoquinoline

Product 1

HCID 867113191-Methyl-5-(pyridin-4-yl)-3,4-dihydroisoquinolineYield 73.8%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Procedure

A mixture of 5-iodo-1-methyl-3,4-dihydroisoquinoline (3.0 g, 11.1 mmol), pyridin-4-ylboronic acid (2.04 g, 16.6 mmol), Pd(PPh3)2Cl2 (3.88 g, 5.53 mmol) and Cs2CO3 (10.8 g, 33.2 mmol) in 1,4-dioxane (45 mL) was heated to reflux for 24 h. The mixture was allowed to cool to RT, and then filtered. The filter cake was washed with AcOEt, and the filtrate was then concentrated in vacuo. The crude product was purified by flash chromatography (SiO2, DCM to DCM/MeOH 9:1) to afford the title compound (1.82 g) as a grey solid. UPLC-MS: MS 223.0 (M+H+); UPLC rt 0.38 min.

Workup

  1. temperaturewas heated
  2. temperatureto reflux for 24 h
  3. filtrationfiltered
  4. washThe filter cake was washed with AcOEt
  5. concentrationthe filtrate was then concentrated in vacuo
  6. customThe crude product was purified by flash chromatography (SiO2, DCM to DCM/MeOH 9:1)

Sources & evidence

ORD record
ord-8f7e61e86c7647dfaabf4cbc67099387
Source dataset
uspto-grants-2016_03
Patent number
US09284331B2

Reaction notes

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