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

HRID 506976Notes

Reaction equation

HRID 506976 reaction equation
FC(F)(F)S(O[C:7]1[CH:16]=[C:15]2[C:10]([CH:11]=[CH:12][N:13]([C:18]3[CH:23]=[C:22]([C:24]([NH:26][CH:27]4[CH2:29][CH2:28]4)=[O:25])[CH:21]=[CH:20][C:19]=3[CH3:30])[C:14]2=[O:17])=[CH:9][CH:8]=1)(=O)=O.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+].[CH3:85][N:86]1[CH2:91][CH2:90][NH:89][CH2:88][CH2:87]1>C(OCC)(=O)C.C([O-])(=O)C.[Pd+2].C([O-])(=O)C.C1(C)C=CC=CC=1>[CH:27]1([NH:26][C:24](=[O:25])[C:22]2[CH:21]=[CH:20][C:19]([CH3:30])=[C:18]([N:13]3[CH:12]=[CH:11][C:10]4[C:15](=[CH:16][C:7]([N:89]5[CH2:90][CH2:91][N:86]([CH3:85])[CH2:87][CH2:88]5)=[CH:8][CH:9]=4)[C:14]3=[O:17])[CH:23]=2)[CH2:29][CH2:28]1

Participants

8

Reactant 4

HCID 10796Cesium carbonateHCID 531671-MethylpiperazineHCID 634876Binap, (A+-)-HCID 866208532-{5-[(Cyclopropylamino)carbonyl]-2-methylphenyl}-1-oxo-1,2-dihydroisoquinolin-7-yl trifluoromethanesulfonate

Product 1

HCID 11654601N-cyclopropyl-4-methyl-3-[7-(4-methylpiperazin-1-yl)-1-oxoisoquinolin-2(1H)-yl]benzamide

Reagents, catalysts & solvents 3

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

Conditions

Temperature
95 °C

Procedure

2-{5-[(Cyclopropylamino)carbonyl]-2-methylphenyl}-1-oxo-1,2-dihydroisoquinolin-7-yl trifluoromethanesulfonate (58 mg), palladium acetate (3 mg), BINAP (16 mg) and cesium carbonate (101 mg) were placed in a reaction tube under an atmosphere of argon. Toluene (0.5 ml) was added followed by N-methylpiperazine (0.041 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 RP-HPLC (5-95% MeCN: 1% NH4OH in H2O, 21 ml/min using a Waters Xterra Prep RP18 5 micron, 19×100 mm column) gave N-cyclopropyl-4-methyl-3-[7-(4-methylpiperazin-1-yl)-1-oxoisoquinolin-2(1H)-yl]benzamide (17 mg) as a pale yellow solid; NMR Spectrum: (DMSOd6) 0.55 (m, 2H), 0.69 (m, 2H), 2.09 (s, 3H), 2.29 (s, 3H), 2.56 (m, 4H), 2.85 (m, 1H), 3.29 (m, 4H), 6.65 (d, 1H), 7.11 (d, 1H), 7.48 (d, 1H), 7.52 (d, 1H), 7.61 (m, 2H), 7.74 (s, 1H), 7.87 (d, 1H), 8.43 (d, 1H); Mass Spectrum: M+H+ 417.

Workup

  1. washwashed with water (2×), brine
  2. dry with materialdried (magnesium sulfate)
  3. concentrationconcentrated
  4. customPurification by RP-HPLC (5-95% MeCN

Sources & evidence

ORD record
ord-44bb96416c564dd9ada94629ca69add6
Source dataset
uspto-grants-2010_08
Patent number
US07786115B2

Reaction notes

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