Synthetic methods of making (2H-1, 2, 3-triazol-2-yl) phenyl compounds as orexin receptor modulators
AssigneeJanssen Pharmaceutica NV
InventorsDominique Paul M Depre, Kiran Matcha, Florian Damien Medina, Pieter Westerduin, Cheng Yi Chen
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Abstract
Processes for preparing (((3aR,6aS)-5-(4,6-dimethylpyrimidin-2-yl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)(2-fluoro-6-(2H-1,2,3-triazol-2-yl)phenyl)methanone are described, which are useful for commercial manufacturing. Said compound is an orexin receptor modulator and may be useful in pharmaceutical compositions and methods for the treatment of diseased states, disorders, and conditions mediated by orexin activity, such as insomnia and depression.
Claims9
A process of preparing (((3aR,6aS)-5-(4,6-dimethylpyrimidin-2-yl)hexahydropyrrolo[3,4-c]pyrrol-2(1H)-yl)(2-fluoro-6-(2H-1,2,3-triazol-2-yl)phenyl)methanone:
- said process comprising step described below:
- cyclization of a hydrazine of Formula I to give a 2-phenyl-2H-1,2,3-triazole of Formula II in a single step:
- wherein:
- R1 is —H, —CO2H, or —CO2C(1-4)alkyl;
- and
- X is —OC(1-2)alkyl, —OCH2Ph, OC(CH3)3, —N(CH3)2, or —N(CH3)3I.
A method of making a compound of Formula I:
- said method comprises:
- reaction of (3-fluorophenyl) hydrazine hydrochloride with glyoxal, in the presence of water and/or methanol, to form (E)-2-(2-(3-fluorophenyl)hydrazono)acetaldehyde in over 90% yield;
- wherein:
- R1 is H, CO2H, or —CO2C(1-4)alkyl;
- and
- X is —OC(1-2)alkyl, —OC(CH3)3, —OCH2Ph, —N(CH3)2, or —N(CH3)3I.
A compound of Formula III:
- wherein R1 is H, CO2H, or —CO2C(1-4)alkyl.
A compound selected from the group consisting of:
Dependencies are inferred from the claim text.