Toluene → 1-methylethyl ((cis)-1-acetyl-6-{1-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-1H-pyrazol-4-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate

HRID 2366836

Reaktionsgleichung

Reaktionsgleichung von HRID 2366836
Br[C:2]1[CH:3]=[N:4][N:5]([CH2:7][CH2:8][N:9]2[C:17](=[O:18])[C:16]3[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=3)[C:10]2=[O:19])[CH:6]=1.[CH3:20][CH:21]([O:23][C:24](=[O:49])[NH:25][CH:26]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33](B3OC(C)(C)C(C)(C)O3)[CH:34]=2)[N:29]([C:45](=[O:47])[CH3:46])[CH:28]([CH3:48])[CH2:27]1)[CH3:22].C(=O)([O-])[O-].[K+].[K+].C1(C)C=CC=CC=1>C(O)C.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>[CH3:22][CH:21]([O:23][C:24](=[O:49])[NH:25][C@H:26]1[C:35]2[C:30](=[CH:31][CH:32]=[C:33]([C:2]3[CH:3]=[N:4][N:5]([CH2:7][CH2:8][N:9]4[C:17](=[O:18])[C:16]5[C:11](=[CH:12][CH:13]=[CH:14][CH:15]=5)[C:10]4=[O:19])[CH:6]=3)[CH:34]=2)[N:29]([C:45](=[O:47])[CH3:46])[C@@H:28]([CH3:48])[CH2:27]1)[CH3:20]

Komponenten

7

Edukt 4

HCID 1140TolueneHCID 11430Potassium CarbonateHCID 53216871N-(2-(4-Bromopyrazol-1-yl)ethyl)phthalimideHCID 774200021-Methylethyl [1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate2×

Produkt 1

HCID 671987031-methylethyl ((cis)-1-acetyl-6-{1-[2-(1,3-dioxo-1,3-dihydro-2H-isoindol-2-yl)ethyl]-1H-pyrazol-4-yl}-2-methyl-1,2,3,4-tetrahydro-4-quinolinyl)carbamate

Reagenzien, Katalysatoren, Lösungsmittel 2

HCID 178418397HCID 178418397, VerbindungKatalysatorHCID 702EthanolLösungsmittel

Versuchsvorschrift

2-[2-(4-bromo-1H-pyrazol-1-yl)ethyl]-1H-isoindole-1,3(2H)-dione (for a preparation see Intermediate 28) (80 mg, 0.250 mmol) and 1-methylethyl[1-acetyl-2-methyl-6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1,2,3,4-tetrahydro-4-quinolinyl]carbamate (Intermediate 12, 150 mg, 0.360 mmol) were mixed with potassium carbonate (69.1 mg, 0.500 mmol) and tetrakis(triphenylphosphine)palladium(0) (14.44 mg, 0.012 mmol), dissolved in ethanol (1 mL) and toluene (1 mL) and stirred under nitrogen at 90° C. for 1 hour. The mixture was partitioned between distilled water (20 mL) and EtOAc (60 mL). The aqueous layer was extracted with EtOAc (60 mL) and the organic fractions were combined, washed (brine, 30 mL), dried (MgSO4), filtered and evaporated to dryness to give a yellow solid which was loaded on to a 12+M Biotage silica column and eluted with cyclohexane:ethyl acetate (3:1 to 1:2). Product-containing fractions were evaporated to dryness to give a solid (39 mg). LCMS (Method C): Rt=0.95, MH+=530

Aufarbeitung

  1. customThe mixture was partitioned
  2. distillationbetween distilled water (20 mL) and EtOAc (60 mL)
  3. extractionThe aqueous layer was extracted with EtOAc (60 mL)
  4. washwashed (brine, 30 mL)
  5. dry with materialdried (MgSO4)
  6. filtrationfiltered
  7. customevaporated to dryness
  8. customto give a yellow solid which
  9. washeluted with cyclohexane:ethyl acetate (3:1 to 1:2)
  10. customProduct-containing fractions were evaporated to dryness

Quellen und Nachweise

ORD-Eintrag
ord-da7f7019cf4c407d86333f19583d6083
Quelldatensatz
uspto-grants-2014_04
Patentnummer
US08697725B2

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