Toluene → 3-(Isoquinolin-3-yl)-4-methylaniline

HRID 1890734Notes

Reaction equation

HRID 1890734 reaction equation
[NH2:1][C:2]1[CH:3]=[CH:4][C:5]([CH3:17])=[C:6](B2OC(C)(C)C(C)(C)O2)[CH:7]=1.Cl[C:19]1[N:20]=[CH:21][C:22]2[C:27]([CH:28]=1)=[CH:26][CH:25]=[CH:24][CH:23]=2.C1(C)C=CC=CC=1.C([O-])([O-])=O.[Na+].[Na+]>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.CCO>[CH:21]1[C:22]2[C:27](=[CH:26][CH:25]=[CH:24][CH:23]=2)[CH:28]=[C:19]([C:6]2[CH:7]=[C:2]([CH:3]=[CH:4][C:5]=2[CH3:17])[NH2:1])[N:20]=1

Participants

7

Reactant 4

HCID 1140TolueneHCID 10340Sodium CarbonateHCID 6409683-ChloroisoquinolineHCID 160860894-Methyl-3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline

Product 1

HCID 583178853-(Isoquinolin-3-yl)-4-methylaniline

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 702EthanolSolvent

Conditions

Temperature
90 °C

Procedure

To a round-bottom flask containing 5-amino-2-methyl-phenylboronic acid pinacol ester (233 mg, 1 mmol), 3-chloro-isoquinoline (245 mg, 1.5 mmol), Pd(PPh3)4 (128 mg, 0.1 mmol) is added toluene (4 ml), EtOH (1 ml) and aqueous 2M Na2CO3 solution (2 ml). The flask is purged with argon and sealed. The mixture is stirred at 90° C. for 18 hours, cooled to room temperature and extracted using water and ethyl acetate. The organic layer is separated, washed with brine, dried over MgSO4 and concentrated. The residue is subjected to silica gel flash chromatography, eluted with ethyl acetate in hexanes from 30% to 50% to afford 3-(isoquinolin-3-yl)-4-methylaniline as a brown oil. LC-MS m/z: 235.1 (M+1).

Workup

  1. customThe flask is purged with argon
  2. customsealed
  3. temperaturecooled to room temperature
  4. extractionextracted
  5. customThe organic layer is separated
  6. washwashed with brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated
  9. washeluted with ethyl acetate in hexanes from 30% to 50%

Sources & evidence

ORD record
ord-77bd56dcd6fe46cf854d539285089f4a
Source dataset
uspto-grants-2013_08
Patent number
US08507491B2

Reaction notes

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