Reaktionsgleichung
N1C2C(=CC=CC=2)C=C1C1C2C(=NC=CC=2)NN=1.[Br:19][C:20]1[CH:21]=[CH:22][C:23]([F:26])=[N:24][CH:25]=1.[Li+].CC([N-]C(C)C)C.[CH:35](N1CCCCC1)=[O:36]>>[Br:19][C:20]1[CH:25]=[N:24][C:23]([F:26])=[C:22]([CH:21]=1)[CH:35]=[O:36]Komponenten
Versuchsvorschrift
Scheme 3 describes a method for preparation of 3-(1H-indol-2-yl)-1H-pyrazolo[3,4-b]pyridine derivatives (XXVII) by first selective deprotonation at position-3 of 5-bromo-2-fluoropyridine (XVII) with LDA followed by N-formylpiperidine quench to produce 5-bromo-2-fluoronicotinaldehyde (XVIII). Aldehyde XVIII was condensed with pinacol followed by nucleophilic aromatic substitution by hydrazine to give 5-bromo-2-hydrazinyl-3-(4,4,5,5-tetramethyl-1,3-dioxolan-2-yl)pyridine (XIX). XIX was then cyclized under acidic conditions to yield 5-bromo-1H-pyrazolo[3,4-b]pyridine (XX). The 1H-pyrazolo[3,4-b]pyridine NH was THP protection followed by reaction of the bromide (XXI) with bis(pinacolato)diboron to form the borate ester (XXII). Suzuki coupling with various bromides (XVIII) or chlorides yields 1H-pyrazolo[3,4-b]pyridine derivatives (XXIII). Iodization of position-3 of 1H-pyrazolo[3,4-b]pyridine (XXIII) with N-iodosuccinimide followed by Suzuki Coupling with various Boc-protected 1H-indol-2-ylboronic acids (XXV) to produce (XXVI). Final deprotection of the pyrazole and indole nitrogens yields the desired 3-(1H-indol-2-yl)-1H-pyrazolo[3,4-b]pyridine derivatives (XXVII).
Aufarbeitung
- customquench
Quellen und Nachweise
- ORD-Eintrag
- ord-28452a372e3d4bf1901d3e3f8bd0c203
- Quelldatensatz
- uspto-grants-2014_09
- Patentnummer
- US08846714B2
Verknüpfte Notizen
Wird geladen…