Toluene → 4-Benzyloxy-1-pyridin-2-yl-isoquinoline-3-carboxylic acid butyl ester

HRID 523840Notes

Reaction equation

HRID 523840 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1B(O)O.C1(C)C=CC=CC=1.[CH2:17]([O:21][C:22]([C:24]1[N:25]=[C:26](Br)[C:27]2[C:32]([C:33]=1[O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:23])[CH2:18][CH2:19][CH3:20].C([O-])([O-])=O.[Na+].[Na+]>CCO.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:17]([O:21][C:22]([C:24]1[N:25]=[C:26]([C:2]2[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=2)[C:27]2[C:32]([C:33]=1[O:34][CH2:35][C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][CH:37]=1)=[CH:31][CH:30]=[CH:29][CH:28]=2)=[O:23])[CH2:18][CH2:19][CH3:20]

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 2762745Pyridine-2-boronic acidHCID 860145034-Benzyloxy-1-bromo-isoquinoline-3-carboxylic acid butyl ester

Product 1

HCID 667133694-Benzyloxy-1-pyridin-2-yl-isoquinoline-3-carboxylic acid butyl ester

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Procedure

To a solution of Pyridin-2-ylboronic acid (323 mg, 2.5 mmol) in EtOH (2.5 ml) was added subsequently toluene (15 ml), 4-Benzyloxy-1-bromo-isoquinoline-3-carboxylic acid butyl ester (1.035 mg, 2.5 mmol, see example D-86a), Pd(PPh3)4 (292 mg, 0.25 mmol), and aq. 2 M Na2CO3 solution (2.5 ml, 5 mmol). The mixture was then refluxed with stirring under N2 protection for 24 h. Subsequently, the mixture was concentrated in vacuo. To the residue was added water (15 ml) and the mixture was extracted with EtOAc (30 ml). The organic phase was dried over MgSO4 and evaporated in vacuo. Purification of the residue by flash column chromatography on silica gel using CH2Cl2 MeOH=98 2 as the eluent gave a dark oil that was further purified by flash column chromatography on silica gel using CH2Cl2 MeOH=99 1 as the eluent and subsequently by preparative TLC using CH2Cl2 MeOH=98 2 as the eluent (had to be repeated several times) to give the title compound as a yellow oil (19 mg); MS-(+)-ion M+1=413.2.

Workup

  1. temperatureThe mixture was then refluxed
  2. concentrationSubsequently, the mixture was concentrated in vacuo
  3. additionTo the residue was added water (15 ml)
  4. extractionthe mixture was extracted with EtOAc (30 ml)
  5. dry with materialThe organic phase was dried over MgSO4
  6. customevaporated in vacuo
  7. customPurification of the residue by flash column chromatography on silica gel
  8. customgave a dark oil that
  9. customwas further purified by flash column chromatography on silica gel

Sources & evidence

ORD record
ord-2e6a11e2128647758a5a2c1f3f3aadde
Source dataset
uspto-grants-2016_05
Patent number
US09339527B2

Reaction notes

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