Cesium carbonate → methyl 4-methyl-3-[7-(4-methylpiperazin-1-yl)-1-oxoisoquinolin-2(1H)-yl]benzoate

HRID 506982Notes

Reaction equation

HRID 506982 reaction equation
[CH3:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[N:12]1[CH:21]=[CH:20][C:19]2[C:14](=[CH:15][C:16](OS(C(F)(F)F)(=O)=O)=[CH:17][CH:18]=2)[C:13]1=[O:30].C1C=CC(P(C2C(C3C(P(C4C=CC=CC=4)C4C=CC=CC=4)=CC=C4C=3C=CC=C4)=C3C(C=CC=C3)=CC=2)C2C=CC=CC=2)=CC=1.C(=O)([O-])[O-].[Cs+].[Cs+].[CH3:83][N:84]1[CH2:89][CH2:88][NH:87][CH2:86][CH2:85]1>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH3:1][C:2]1[CH:11]=[CH:10][C:5]([C:6]([O:8][CH3:9])=[O:7])=[CH:4][C:3]=1[N:12]1[CH:21]=[CH:20][C:19]2[C:14](=[CH:15][C:16]([N:87]3[CH2:88][CH2:89][N:84]([CH3:83])[CH2:85][CH2:86]3)=[CH:17][CH:18]=2)[C:13]1=[O:30]

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 531671-MethylpiperazineHCID 634876Binap, (A+-)-HCID 86620854methyl 4-methyl-3-[1-oxo-7-{[(trifluoromethyl)sulfonyl]oxy} isoquinolin-2(1H)-yl]benzoate

Product 1

HCID 67018576methyl 4-methyl-3-[7-(4-methylpiperazin-1-yl)-1-oxoisoquinolin-2(1H)-yl]benzoate

Reagents, catalysts & solvents 3

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
95 °C

Procedure

Methyl 4-methyl-3-[1-oxo-7-{[(trifluoromethyl)sulfonyl]oxy} isoquinolin-2(1H)-yl]benzoate (243 mg), palladium acetate (12 mg), BINAP (69 mg), and cesium carbonate (449 mg) were placed in a reaction tube under an atmosphere of argon. Toluene (2.5 ml) was added followed by N-methylpiperazine (0.183 ml) and the reaction mixture was stirred in a sealed tube at 95° C. for 16 hours. The reaction mixture was diluted with ethyl acetate and washed with water (2×), brine, dried (magnesium sulfate) and concentrated. Purification by column chromatography on an ion exchange column (isolute SCX column from International Sorbent Technology Limited, Henoed, Mid-Glamorgan, UK) using initially methanol and then a 99:1 mixture of methanol and aqueous ammonia solution gave methyl 4-methyl-3-[7-(4-methylpiperazin-1-yl)-1-oxoisoquinolin-2(1H)-yl]benzoate as a brown solid (189 mg); NMR Spectrum: (DMSOd6) 2.12 (s, 3H), 2.23 (s, 3H), 2.50 (m, 4H), 3.25 (m, 4H), 3.88 (s, 3H), 6.65 (d, 1H), 7.12 (d, 1H), 7.52-7.60 (m, 3H), 7.63 (d, 1H), 7.80 (s, 1H), 7.99 (d, 1H); Mass Spectrum: M+H+ 392.

Workup

  1. washwashed with water (2×), brine
  2. dry with materialdried (magnesium sulfate)
  3. concentrationconcentrated
  4. customPurification by column chromatography on an ion exchange column (isolute SCX column from International Sorbent Technology Limited, Henoed, Mid-Glamorgan, UK)
  5. additiona 99:1 mixture of methanol and aqueous ammonia solution

Sources & evidence

ORD record
ord-8161d0ffefa6417fb3acd78ad1ea8a16
Source dataset
uspto-grants-2010_08
Patent number
US07786115B2

Reaction notes

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