Back to results
US 10,870,637 B2Granted
Process for the preparation of a sulfonamide structured kinase inhibitor
AssigneeOrion Corporation
InventorsOskari Karjalainen, Pekka Pietikäinen
Life of this patent
Estimating the term…
Abstract
The present disclosure relates to an improved process for the preparation of a sulfonamide structured kinase inhibitor, namely N-(2′,4′-difluoro-5-(5-(1-methyl-1H-pyrazol-4-yl)-1H-benzo[d]imidazol-1-yl)-[1,1′-biphenyl]-3-yl)cyclopropanesulfonamide (1A) and pharmaceutically acceptable salts thereof. Compound of formula (1A) is a selective inhibitor of FGFR/VEGFR kinase families and is useful in the treatment of cancer.
Claims20
A process for the preparation of a compound of formula (1A), or a pharmaceutically acceptable salt thereof:
- comprising the steps of:
- a) reacting 2′,4′-difluoro-[1,1′-biphenyl]-3,5-diami ne of formula (V)
- with 4-bromo-2-fluoronitrobenzene in the presence of an organic base and an organosilane, to obtain a compound of formula (IV)
- b) treating the product obtained from step (a) with an organic acid and isolating the formed organic salt;
- c) releasing the compound of formula (IV) from its salt form;
- d) either (i) reacting the compound of formula (IV) with cyclopropanesulfonyl chloride to obtain a compound of formula (III)
- and subsequently reacting the compound of formula (III) with 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole;
- or
- (ii) reacting the compound of formula (IV) with 1-methyl-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1H-pyrazole to obtain a compound of formula (IIIb)
- and subsequently reacting the compound of formula (IIIb) with cyclopropane-sulfonyl chloride;
- to obtain a compound of formula (II);
- e) hydrogenating the compound of formula (II) in formic acid in the presence of a catalyst to obtain the compound of formula (1A), which is optionally converted to its pharmaceutically acceptable salt.
9 more elements
Dependencies are inferred from the claim text.