Activated carbon monolith catalyst including a finished self-supporting activated carbon monolith having at least one passage therethrough, and including a supporting matrix and substantially discontinuous activated carbon particles dispersed throughout the supporting matrix and at least one catalyst precursor on the finished self-supporting activated carbon monolith. A method for making, and a method for use, of such an activated carbon monolith catalyst in catalytic chemical reactions.

The invention relates to a method for synthesis of 1-[2-(2,4-Dimethyl-phenylsulfanyl)-phenyl]piperazine in the presence of a strong base.

To an appropriate reactor equipped with mechanical stirrer was charged acetic acid (12 L), tert-butyl 4-(3-(6-(3,5-dimethoxyphenyl)-2-(methylthio)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)propyl)piperazine-1-carboxylate (2000 g) and triethylamine (639 g, 2.3 eq.). Internal temperature was adjusted to approximately 20 C. and N-chlorosuccinimide (1651 g, 4.5 eq.) was added at 20-30 C. Reaction was stirred for 2 hours. Ethyl acetate (30 L) was added. 5% aqueous NaCl solution (20 L) was added. The organic layer was separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with 30% aqueous potassium carbonate solution (14 L). The organic layer was concentrated to 12 L and used for next step directly.

To an appropriate reactor equipped with mechanical stirrer was charged acetic acid (12 L), tert-butyl 4-(3-(6-(3,5-dimethoxyphenyl)-2-(methylthio)-7-oxopyrido[2,3-d]pyrimidin-8(7H)-yl)propyl)piperazine-1-carboxylate (2000 g) and triethylamine (639 g, 2.3 eq.). Internal temperature was adjusted to approximately 20 C. and N-chlorosuccinimide (1651 g, 4.5 eq.) was added at 20-30 C. Reaction was stirred for 2 hours. Ethyl acetate (30 L) was added. 5% aqueous NaCl solution (20 L) was added. The organic layer was separated and the aqueous layer was extracted with EtOAc. The combined organic layers were washed with 30% aqueous potassium carbonate solution (14 L). The organic layer was concentrated to 12 L and used for next step directly.

In one aspect, the disclosure relates to a method for the direct synthesis of complex N,N,O-trisubstituted hydroxylamines by NO bond formation. In another aspect, the method can successfully be employed using a wide variety of commercially available alcohols and secondary amines and enables the construction of large fragment-based libraries of trisubstituted hydroxylamines for drug discovery purposes. Also disclosed are N,N,O-trisubstituted hydroxylamines having low basicity, high stability at ambient temperatures, and an inherent lack of reactivity towards acetylating and sulfonylating enzymes that confer mutagenicity on less-substituted hydroxylamines.

The present invention relates to a novel route of synthesis for the opioid receptor antagonist Buprenorphine or a pharmaceutically acceptable salt thereof, starting from thebaine, wherein the route comprises the reaction of thebaine with a dienophile; forming an alkylated reaction product by reaction with a Grignard-reagent; formation of an cyanamide; deprotection of the cyanamide- and the phenolic-oxygen-moiety, wherein the cleavage of one or both groups is performed in the presence of an alkali or alkaline earth sulfide; followed by derivatization with a cyclopropyl-halogen and hydrogenation to yield Buprenorphine.

The present invention relates to a novel route of synthesis for the opioid receptor antagonist Buprenorphine or a pharmaceutically acceptable salt thereof, starting from thebaine, wherein the route comprises the reaction of thebaine with a dienophile; forming an alkylated reaction product by reaction with a Grignard-reagent; formation of an cyanamide; deprotection of the cyanamide- and the phenolic-oxygen-moiety, wherein the cleavage of one or both groups is performed in the presence of an alkali or alkaline earth sulfide; followed by derivatization with a cyclopropyl-halogen and hydrogenation to yield Buprenorphine.

The present invention relates to a novel route of synthesis for the opioid receptor antagonist Buprenorphine or a pharmaceutically acceptable salt thereof, starting from thebaine, wherein the route comprises the reaction of thebaine with a dienophile; forming an alkylated reaction product by reaction with a Grignard-reagent; formation of an cyanamide; deprotection of the cyanamide- and the phenolic-oxygen-moiety, wherein the cleavage of one or both groups is performed in the presence of an alkali or alkaline earth sulfide; followed by derivatization with a cyclopropyl-halogen and hydrogenation to yield Buprenorphine.

The present invention provides oxalic amide ligands and uses thereof in copper-catalyzed coupling reaction of aryl halides. Specifically, the present invention provides a use of a compound represented by formula I, wherein definitions of each group are described in the specification. The compound represented by formula I can be used as a ligand in copper-catalyzed coupling reaction of aryl halides for the formation of CN, CO and CS bonds. ##STR00001##

The present invention provides oxalic amide ligands and uses thereof in copper-catalyzed coupling reaction of aryl halides. Specifically, the present invention provides a use of a compound represented by formula I, wherein definitions of each group are described in the specification. The compound represented by formula I can be used as a ligand in copper-catalyzed coupling reaction of aryl halides for the formation of CN, CO and CS bonds. ##STR00001##