Potassium tert-butoxide → 3-((4-amino-3-(3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one

HRID 1627201Notizen

Reaktionsgleichung

Reaktionsgleichung von HRID 1627201
[CH3:1][O:2][C:3]1[CH:4]=[C:5]([C:9]2[C:17]3[C:12](=[N:13][CH:14]=[N:15][C:16]=3[NH2:18])[NH:11][N:10]=2)[CH:6]=[CH:7][CH:8]=1.CC(C)([O-])C.[K+].Br[CH2:26][C:27]1[N:28]([C:39]2[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=2[CH3:45])[C:29](=[O:38])[C:30]2[C:35]([CH:36]=1)=[CH:34][CH:33]=[CH:32][C:31]=2[CH3:37]>CN(C=O)C>[NH2:18][C:16]1[N:15]=[CH:14][N:13]=[C:12]2[N:11]([CH2:26][C:27]3[N:28]([C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=4[CH3:45])[C:29](=[O:38])[C:30]4[C:35]([CH:36]=3)=[CH:34][CH:33]=[CH:32][C:31]=4[CH3:37])[N:10]=[C:9]([C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([OH:2])[CH:4]=3)[C:17]=12.[NH2:18][C:16]1[N:15]=[CH:14][N:13]=[C:12]2[N:11]([CH2:26][C:27]3[N:28]([C:39]4[CH:44]=[CH:43][CH:42]=[CH:41][C:40]=4[CH3:45])[C:29](=[O:38])[C:30]4[C:35]([CH:36]=3)=[CH:34][CH:33]=[CH:32][C:31]=4[CH3:37])[N:10]=[C:9]([C:5]3[CH:6]=[CH:7][CH:8]=[C:3]([O:2][CH3:1])[CH:4]=3)[C:17]=12

Komponenten

6

Edukt 3

HCID 23665647Potassium tert-butoxideHCID 580086503-(Bromomethyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-oneHCID 1784899393-(3-Methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Produkt 2

HCID 580086943-((4-amino-3-(3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-oneAusbeute 139,3 %HCID 580087113-((4-amino-3-(3-hydroxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 6228DimethylformamideLösungsmittel

Versuchsvorschrift

3-(3-Methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-amine (1701) (964 mg, 4 mmol) and potassium tert-butoxide (0.44 g, 4 mmol) were dissolved in anhydrous DMF (150 mL) and stirred at RT for 30 min. 3-(Bromomethyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one (1610) (1.37 g, 4.0 mmol) was added. The resulting mixture was stirred at RT for 30 min, poured into ice water (30 mL) and then extracted with ethyl acetate (3×50 mL). The combined organic layer was washed with brine (25 mL), dried over Na2SO4 and filtered. The filtrate was concentrated in vacuo and the residue was purified by flash column chromatography on silica gel (2-20% MeOH/DCM) to afford the desired product, 3-((4-amino-3-(3-methoxyphenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)methyl)-8-methyl-2-o-tolylisoquinolin-1(2H)-one (1702) (1.4 g, 70% yield) as a white solid.

Aufarbeitung

  1. stirringThe resulting mixture was stirred at RT for 30 min
  2. extractionextracted with ethyl acetate (3×50 mL)
  3. washThe combined organic layer was washed with brine (25 mL)
  4. dry with materialdried over Na2SO4
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated in vacuo
  7. customthe residue was purified by flash column chromatography on silica gel (2-20% MeOH/DCM)

Quellen und Nachweise

ORD-Eintrag
ord-4bf27aa2efdd4a92b1108c54a54bd30c
Quelldatensatz
uspto-grants-2014_07
Patentnummer
US08785456B2

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