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3,4-Dimethylaniline → Methyl 4-[(3,4-dimethylphenyl)amino]-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinecarboxylate

HRID 572515
Notes
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Reaction equation

HRID 572515 reaction equation
[CH3:1][N:2]1[C:11]([C:12]([O:14][CH3:15])=[O:13])=[C:10](OS(C(F)(F)F)(=O)=O)[C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=[O:24].[CH3:25][C:26]1[CH:27]=[C:28]([NH2:33])[CH:29]=[CH:30][C:31]=1[CH3:32].C(=O)([O-])[O-].[Cs+].[Cs+].CC1C2OC3C(=CC=CC=3)CC=2C(P(C2C=CC=CC=2)C2C=CC=CC=2)=C(P(C2C=CC=CC=2)C2C=CC=CC=2)C=1C>O1CCOCC1.C(OCC)C.CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:25][C:26]1[CH:27]=[C:28]([NH:33][C:10]2[C:9]3[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=3)[C:3](=[O:24])[N:2]([CH3:1])[C:11]=2[C:12]([O:14][CH3:15])=[O:13])[CH:29]=[CH:30][C:31]=1[CH3:32]
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

8

Reactant 4

HCID 72483,4-DimethylanilineHCID 10796Cesium carbonateHCID 57370308Dimethyl bis diphenylphosphino xantheneHCID 86700721Methyl 2-methyl-1-oxo-4-{[(trifluoromethyl)sulfonyl]oxy}-1,2-dihydro-3-isoquinolinecarboxylate

Product 1

HCID 68295443Methyl 4-[(3,4-dimethylphenyl)amino]-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinecarboxylate
Yield 76.3%

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 3283Diethyl EtherSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

To a solution of methyl 2-methyl-1-oxo-4-{[(trifluoromethyl)sulfonyl]oxy}-1,2-dihydro-3-isoquinolinecarboxylate (0.84 g, 2.3 mmol) and (3,4-dimethylphenyl)amine (0.362 g, 2.99 mmol) in 1,4-dioxane (25 mL) under nitrogen was added cesium carbonate (1.124 g, 3.45 mmol), dimethylbisdiphenylphosphinoxanthene (0.103 g, 0.172 mmol) and Pd(OAc)2 (0.026 g, 0.115 mmol) and the mixture was stirred at 100° C. for 16 hours. The mixture was diluted with diethyl ether, filtered through Celite and the filter cake was washed with diethyl ether. The crude product was purified on silica using EtOAc/hexanes 10-30% to provide the title compound as a yellow solid (0.59 g, 74%). 1H NMR (400 MHz, CDCl3) δ ppm 8.48 (dd, J=1.2, 5.9 Hz, 1 H), 7.69-7.52 (m, 3 H), 6.89 (d, J=8.2 Hz, 1 H), 6.55-6.29 (m, 2 H), 5.66 (s, 1 H), 3.86 (s, 3 H), 3.62-3.51 (m, 3 H), 3.57 (s, 4 H), 2.14 (s, 9 H), 2.24-2.07 (m, 6 H), 1.56 (s, 3 H);); ES-LCMS: 337.3 (M+1).

Workup

  1. filtrationfiltered through Celite
  2. washthe filter cake was washed with diethyl ether
  3. customThe crude product was purified on silica

Sources & evidence

ORD record
ord-605ae13b083044e0b0ec092ea85d7b58
Source dataset
uspto-grants-2015_05
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US09029391B2

Reaction notes

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On this pageParticipantsConditionsProcedureWorkupSources & evidenceReaction notes