Processes
AssigneeInflazome Limited
InventorsDaniel Schwizer, Sascha Breeger, Stephen Thom, Thomas Alanine
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Abstract
The present invention relates to processes of preparing N-((1,2,3,4,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-1-iso-propyl-1H-pyrazole-3-sulfonamide and salts thereof. The present invention further relates to pharmaceutical compositions comprising such compounds and to the use of such compounds in the treatment and prevention of medical disorders and diseases, most especially by NLRP3 inhibition.
Claims11
A process of preparing N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-1-isopropyl-1H-pyrazole-3-sulfonamide or a salt thereof, comprising the step of contacting 1-isopropyl-3-(alkoxycarbonylaminosulfonyl)-1H-pyrazole with 1,2,3,5,6,7-hexahydro-s-indacen-4-amine in the presence of a solvent to obtain N-((1,2,3,5,6,7-hexahydro-s-indacen-4-yl)carbamoyl)-1-isopropyl-1H-pyrazole-3-sulfonamide:
- wherein R is C1-6 alkyl.
A process of preparing 1-isopropyl-3-(alkoxycarbonylaminosulfonyl)-1H-pyrazole:
- wherein R is C1-6 alkyl, comprising one or more steps selected from:
- (a) contacting 3-nitro-1H-pyrazole with iPr-X to obtain 1-isopropyl-3-nitro-1H-pyrazole, wherein X is a leaving group:
- (b) reducing 1-isopropyl-3-nitro-1H-pyrazole to obtain 1-isopropyl-3-amino-1H-pyrazole:
- (c) converting 1-isopropyl-3-amino-1H-pyrazole into 1-isopropyl-3-iodo-1H-pyrazole:
- (d) converting 1-isopropyl-3-iodo-1H-pyrazole into 1-isopropyl-1H-pyrazole-3-sulfonamide:
- and
- (e) converting 1-isopropyl-1H-pyrazole-3-sulfonamide into 1-isopropyl-3-(alkoxycarbonylaminosulfonyl)-1H-pyrazole:
A process of preparing 1,2,3,5,6,7-hexahydro-s-indacen-4-amine:
- wherein the process is suitable for large scale clinical manufacture and comprises one or more steps selected from:
- (i) contacting 2,3-dihydro-1H-indene with YCH2CH2COZ to obtain a substituted 1-(2,3-dihydro-1H-inden-5-yl)propan-1-one, wherein Y and Z are leaving groups:
- (ii) contacting the substituted 1-(2,3-dihydro-1H-inden-5-yl)propan-1-one with an acid to obtain 1,2,3,5,6,7-hexahydro-s-indacen-1-one:
- (iii) converting 1,2,3,5,6,7-hexahydro-s-indacen-1-one into 4-nitro-1,2,3,5,6,7-hexahydro-s-indacen-1-one and/or 8-nitro-1,2,3,5,6,7-hexahydro-s-indacen-1-one:
- and
- (iv) reducing 4-nitro-1,2,3,5,6,7-hexahydro-s-indacen-1-one and/or 8-nitro-1,2,3,5,6,7-hexahydro-s-indacen-1-one to obtain 1,2,3,5,6,7-hexahydro-s-indacen-4-amine:
1-Isopropyl-3-(alkoxycarbonylaminosulfonyl)-1H-pyrazole:
- wherein R is C1-6 alkyl.
Dependencies are inferred from the claim text.