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Potassium Carbonate → N-Cyclopropyl-3-fluoro-5-(4-formyl-2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinolin-6-yl)-4-methylbenzamide

HRID 906406
Notizen
Druckvorschau

Reaktionsgleichung

Reaktionsgleichung von HRID 906406
Br[C:2]1[CH:3]=[C:4]2[C:9](=[CH:10][CH:11]=1)[C:8](=[O:12])[N:7]([CH2:13][C:14]([CH3:18])([CH3:17])[CH2:15]Cl)[CH:6]=[C:5]2[CH:19]=[O:20].C([O-])(=[O:23])C.[K+].[CH:26]1([NH:29][C:30](=[O:48])[C:31]2[CH:36]=[C:35](B3OC(C)(C)C(C)(C)O3)[C:34]([CH3:46])=[C:33]([F:47])[CH:32]=2)[CH2:28][CH2:27]1.C(=O)([O-])[O-].[K+].[K+]>CN1C(=O)CCC1.O.CO>[CH:26]1([NH:29][C:30](=[O:48])[C:31]2[CH:36]=[C:35]([C:2]3[CH:3]=[C:4]4[C:9](=[CH:10][CH:11]=3)[C:8](=[O:12])[N:7]([CH2:13][C:14]([CH3:18])([CH3:17])[CH2:15][OH:23])[CH:6]=[C:5]4[CH:19]=[O:20])[C:34]([CH3:46])=[C:33]([F:47])[CH:32]=2)[CH2:27][CH2:28]1
KomponentenReaktionsbedingungenVersuchsvorschriftAufarbeitungQuellen und NachweiseNotizen zur Reaktion

Komponenten

8

Edukt 4

HCID 11430Potassium CarbonateHCID 517044Potassium AcetateHCID 21914563N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamideHCID 866409616-Bromo-2-(3-chloro-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinoline-4-carbaldehyde

Produkt 1

HCID 86640963
N-Cyclopropyl-3-fluoro-5-(4-formyl-2-(3-hydroxy-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinolin-6-yl)-4-methylbenzamide
Ausbeute 87,1 %

Reagenzien, Katalysatoren, Lösungsmittel 3

HCID 887MethanolLösungsmittelHCID 962WaterLösungsmittelHCID 13387N-methyl-2-pyrrolidoneLösungsmittel

Reaktionsbedingungen

Temperatur
130 °C

Versuchsvorschrift

A solution of 6-bromo-2-(3-chloro-2,2-dimethylpropyl)-1-oxo-1,2-dihydroisoquinoline-4-carbaldehyde (Example 2b, 0.50 g) dissolved in NMP (5 mL) was treated with potassium acetate (0.17 g) under nitrogen. The resulting mixture was stirred at 130° C. for 20 h. The mixture was then treated with N-cyclopropyl-3-fluoro-4-methyl-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)benzamide (0.63 g), Pd-118 (0.046 g) and potassium carbonate (0.43 g) under nitrogen and stirred at 80° C. for 4 h. After cooling to room temperature methanol (10 mL) was added and the mixture stirred for 1 h. The reaction mixture was diluted with water (250 mL), and extracted with ethyl acetate (250 mL). The organic was dried (MgSO4), filtered and evaporated to afford crude product. The crude product was purified (SiO2 chromatography, elution with 100% ethyl acetate) to afford the subtitle compound (0.55 g) as an oil.

Aufarbeitung

  1. stirringstirred at 80° C. for 4 h
  2. additionwas added
  3. stirringthe mixture stirred for 1 h
  4. extractionextracted with ethyl acetate (250 mL)
  5. dry with materialThe organic was dried (MgSO4)
  6. filtrationfiltered
  7. customevaporated
  8. customto afford crude product
  9. customThe crude product was purified
  10. wash(SiO2 chromatography, elution with 100% ethyl acetate)

Quellen und Nachweise

ORD-Eintrag
ord-871a6180d7ff4f97925a12c12c54b153
Quelldatensatz
uspto-grants-2011_09
DOI
10.6084/m9.figshare.5104873.v1
Patentnummer
US08012980B2

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