Dimethylformamide → Methyl [(1,1-dimethylethyl)oxy]{4-(3,4-dimethylphenyl)-7-[(ethylamino)carbonyl]-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl}acetate

HRID 572501Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 572501
Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6]([C:24]3[CH:29]=[CH:28][C:27]([CH3:30])=[C:26]([CH3:31])[CH:25]=3)=[C:7]([CH:14]([O:19][C:20]([CH3:23])([CH3:22])[CH3:21])[C:15]([O:17][CH3:18])=[O:16])[N:8]([CH3:13])[C:9]2=[O:12])=[CH:4][CH:3]=1.Cl.[CH2:33]([NH2:35])[CH3:34].CCN(C(C)C)C(C)C.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.CN(C)[CH:76]=[O:77]>CC([O-])=O.CC([O-])=O.[Pd+2]>[CH3:23][C:20]([O:19][CH:14]([C:7]1[N:8]([CH3:13])[C:9](=[O:12])[C:10]2[C:5]([C:6]=1[C:24]1[CH:29]=[CH:28][C:27]([CH3:30])=[C:26]([CH3:31])[CH:25]=1)=[CH:4][CH:3]=[C:2]([C:76]([NH:35][CH2:33][CH3:34])=[O:77])[CH:11]=2)[C:15]([O:17][CH3:18])=[O:16])([CH3:22])[CH3:21]

Komponenten

7

Edukt 5

HCID 6228Dimethylformamide2×HCID 11198Ethylamine hydrochloride2×HCID 812191,3-Bis(diphenylphosphino)propane2×HCID 81531Diisopropylethylamine2×HCID 68295047Methyl [7-bromo-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl][(1,1-dimethylethyl)oxy]acetate

Produkt 1

HCID 68352816Methyl [(1,1-dimethylethyl)oxy]{4-(3,4-dimethylphenyl)-7-[(ethylamino)carbonyl]-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl}acetateAusbeute 28,6 %

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 167845palladium(II) acetateKatalysator2×

Reaktionsbedingungen

Temperatur
80 °C

Versuchsvorschrift

A mixture of methyl [7-bromo-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl][(1,1-dimethylethyl)oxy]acetate (33 mg, 0.068 mmol), ethylamine HCl (11.06 mg, 0.136 mmol), and Hunig's base (47.4 μl, 0.271 mmol) in N,N-Dimethylformamide (DMF) (631 μl) was degassed with N2 for 8 min, and then treated with Pd(OAc)2 (1.5 mg, 6.78 μmol) and 1,3-bis(diphenylphosphino)propane (2.80 mg, 6.78 μmol). The reaction was placed under vacuum, filled and purged with N2 3×, followed by CO 3×. The reaction was stirred at 50 psi (CO) at 80° C. overnight. Additional DMF (1 mL), ethylamine HCl (11.06 mg, 0.136 mmol), and Hunig's base (47.4 μl, 0.271 mmol) were added, the reaction was degassed with N2 for 5 min, treated with Pd(OAc)2 (1.523 mg, 6.78 μmol) and 1,3-bis(diphenylphosphino)propane (2.80 mg, 6.78 μmol), filled and purged with N2 3×, CO 3×, and stirred at 80° C. under 50 psi of CO for 5 hours. The mixture was filtered, extracted with EtOAc, washed with water, brine, dried with Na2SO4, filtered, and concentrated. The residue was purified by column chromatography (0-100% EtOAc/Hexane, followed with 0-20% MeOH/DCM) to afford methyl [(1,1-dimethylethyl)oxy]{4-(3,4-dimethylphenyl)-7-[(ethylamino)carbonyl]-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl}acetate (9.3 mg, 0.019 mmol, 28.6% yield); LC/MS (m/z) ES+=479 (M+1).

Aufarbeitung

  1. customwas degassed with N2 for 8 min
  2. additionfilled
  3. custompurged with N2 3×
  4. customthe reaction was degassed with N2 for 5 min
  5. additionfilled
  6. custompurged with N2 3×, CO 3×
  7. stirringstirred at 80° C. under 50 psi of CO for 5 hours
  8. filtrationThe mixture was filtered
  9. extractionextracted with EtOAc
  10. washwashed with water, brine
  11. dry with materialdried with Na2SO4
  12. filtrationfiltered
  13. concentrationconcentrated
  14. customThe residue was purified by column chromatography (0-100% EtOAc/Hexane, followed with 0-20% MeOH/DCM)

Quellen und Nachweise

ORD-Eintrag
ord-c6ae4fa39ee24c1781dfb212623716c4
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09029391B2

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