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

HRID 572504Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 572504
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.[CH3:32][N:33](C)C=O>O.[C-]#N.[C-]#N.[Zn+2].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>[C:32]([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])([CH3:21])[CH3:22])[C:15]([O:17][CH3:18])=[O:16])[N:8]([CH3:13])[C:9]2=[O:12])=[CH:4][CH:3]=1)#[N:33]

Komponenten

6

Edukt 2

HCID 6228DimethylformamideHCID 68295047Methyl [7-bromo-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl][(1,1-dimethylethyl)oxy]acetate

Produkt 1

HCID 68352905Methyl [7-cyano-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl][(1,1-dimethylethyl)oxy]acetateAusbeute 82 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 11186Zinc cyanide (Zn(CN)2)KatalysatorHCID 178418397HCID 178418397, VerbindungKatalysatorHCID 962WaterLösungsmittel

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 (160 mg, 0.329 mmol) and Zn(CN)2 (38.6 mg, 0.329 mmol) in N,N-Dimethylformamide (DMF) (3289 μl) was degassed with N2 for 5 min, treated with Pd(Ph3P)4 (38.0 mg, 0.033 mmol), and irradiated in microwave at 120° C. for 30 min. The mixture was diluted with water, extracted with EtOAc, washed with water, brine, dried with Na2SO4, filtered, and concentrated. the residue was purified by column chromatography (SiO2, 0-60% EtOAc/Hexane) to afford methyl [7-cyano-4-(3,4-dimethylphenyl)-2-methyl-1-oxo-1,2-dihydro-3-isoquinolinyl][(1,1-dimethylethyl)oxy]acetate (116.8 mg, 0.270 mmol, 82% yield) as colorless oil that slowly became a white solid: 1H NMR (400 MHz, CHLOROFORM-d) δ ppm 8.85-8.76 (m, 1 H), 7.65 (ddd, J=1.9, 6.1, 8.3 Hz, 1 H), 7.30-7.24 (m, 1 H), 7.23-7.09 (m, 2 H), 7.07-6.96 (m, 1 H), 5.22 (s, 1 H), 3.80 (s, 1.5 H), 3.78 (s, 1.5 H), 3.70 (s, 1.5 H), 3.69 (s, 1.5 ; H), 2.37 (s, 3 H), 2.32 (s, 3 H), 1.02 (s, 4.5 H), 1.01 (s, 4.5 H); LCMS (m/z) ES+=433 (M+1).

Aufarbeitung

  1. customwas degassed with N2 for 5 min
  2. customirradiated in microwave at 120° C. for 30 min
  3. extractionextracted with EtOAc
  4. washwashed with water, brine
  5. dry with materialdried with Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated
  8. customthe residue was purified by column chromatography (SiO2, 0-60% EtOAc/Hexane)

Quellen und Nachweise

ORD-Eintrag
ord-a41a4f92fa9c4e4aac6529cdccfab749
Quelldatensatz
uspto-grants-2015_05
Patentnummer
US09029391B2

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