C07C205/57

PROCESS TO PREPARE 3-METHYL-2-NITROBENZOIC ACID BY AIR OXIDATION

A method for preparing 3-methyl-2-nitrobenzoic acid is disclosed wherein 1,3-dimethyl-2-nitrobenzene is combined with an oxidation catalyst in the presence of an oxygen source and an initiator, provided that less than 99% of the 1,3-dimethyl-2-nitrobenzene is oxidized.

A method for preparing compounds of Formula 7 and Formula 11 is also disclosed wherein the method is characterized by using 3-methyl-2-nitrobenzoic acid as prepared by the method disclosed above.

##STR00001##

wherein R.sup.1 is C.sub.1-C.sub.7 alkyl, C.sub.3-C.sub.6 cycloalkyl or C.sub.4-C.sub.7 alkylcycloalkyl

PROCESS TO PREPARE 3-METHYL-2-NITROBENZOIC ACID BY AIR OXIDATION

A method for preparing 3-methyl-2-nitrobenzoic acid is disclosed wherein 1,3-dimethyl-2-nitrobenzene is combined with an oxidation catalyst in the presence of an oxygen source and an initiator, provided that less than 99% of the 1,3-dimethyl-2-nitrobenzene is oxidized.

A method for preparing compounds of Formula 7 and Formula 11 is also disclosed wherein the method is characterized by using 3-methyl-2-nitrobenzoic acid as prepared by the method disclosed above.

##STR00001##

wherein R.sup.1 is C.sub.1-C.sub.7 alkyl, C.sub.3-C.sub.6 cycloalkyl or C.sub.4-C.sub.7 alkylcycloalkyl

Pharmaceutical compositions comprising monoterpenes

The present invention provides a process for purifying a monoterpene or sesquiterpene having a purity greater than about 98.5% (w/w). The process comprises the steps of derivatizing the monoterpene (or sesquiterpene) to produce a monoterpene (or sesquiterpene) derivative, separating the monoterpene (or sesquiterpene) derivative, and releasing the monoterpene (or sesquiterpene) from the derivative. Also encompassed by the scope of the present invention is a pharmaceutical composition comprising a monoterpene (or sesquiterpene) having a purity greater than about 98.5% (w/w). The purified monoterpene can be used to treat a disease such as cancer. The present monoterpene (or sesquiterpene) may be administered alone, or may be co-administered with radiation or other therapeutic agents, such as chemotherapeutic agents.

Pharmaceutical compositions comprising monoterpenes

The present invention provides a process for purifying a monoterpene or sesquiterpene having a purity greater than about 98.5% (w/w). The process comprises the steps of derivatizing the monoterpene (or sesquiterpene) to produce a monoterpene (or sesquiterpene) derivative, separating the monoterpene (or sesquiterpene) derivative, and releasing the monoterpene (or sesquiterpene) from the derivative. Also encompassed by the scope of the present invention is a pharmaceutical composition comprising a monoterpene (or sesquiterpene) having a purity greater than about 98.5% (w/w). The purified monoterpene can be used to treat a disease such as cancer. The present monoterpene (or sesquiterpene) may be administered alone, or may be co-administered with radiation or other therapeutic agents, such as chemotherapeutic agents.

Processes and Intermediates for Preparing a Macrocyclic Protease Inhibitor of HCV

A process for preparing [(1R,2R)-4-oxo-1,2-cyclopentanedicarboxylic acid II, by the resolution of racemic 4-oxo-1,2-cyclopentanedicarboxylic acid (V), said process comprising: (a) reacting 4-oxo-1,2-cyclopentanedicarboxylic acid (V) with brucine or (1R,2S)-()-ephedrine, thus preparing the bis-brucine or bis-(1R,2S)-()-ephedrine salt of (V), and (b) precipitating selectively the bis-brucine or bis-(1R,2S)-()-ephedrine salt of (1R,2R)-4-oxo-1,2-cyclopentanedicarboxylic acid II, while the bis-brucine or bis-(1R,2S)-()-ephedrine salt of [(1S,2S)-4-oxo-1,2-cyclopentanedicarboxylic acid stays in solution; (c) liberating the acid II by removal of brucine or (1R,2S)-()-ephedrine from the precipitated salt obtained in step (b).

Processes and Intermediates for Preparing a Macrocyclic Protease Inhibitor of HCV

A process for preparing [(1R,2R)-4-oxo-1,2-cyclopentanedicarboxylic acid II, by the resolution of racemic 4-oxo-1,2-cyclopentanedicarboxylic acid (V), said process comprising: (a) reacting 4-oxo-1,2-cyclopentanedicarboxylic acid (V) with brucine or (1R,2S)-()-ephedrine, thus preparing the bis-brucine or bis-(1R,2S)-()-ephedrine salt of (V), and (b) precipitating selectively the bis-brucine or bis-(1R,2S)-()-ephedrine salt of (1R,2R)-4-oxo-1,2-cyclopentanedicarboxylic acid II, while the bis-brucine or bis-(1R,2S)-()-ephedrine salt of [(1S,2S)-4-oxo-1,2-cyclopentanedicarboxylic acid stays in solution; (c) liberating the acid II by removal of brucine or (1R,2S)-()-ephedrine from the precipitated salt obtained in step (b).

Processes and Intermediates for Preparing a Macrocyclic Protease Inhibitor of HCV

A process for preparing [(1R,2R)-4-oxo-1,2-cyclopentanedicarboxylic acid II, by the resolution of racemic 4-oxo-1,2-cyclopentanedicarboxylic acid (V), said process comprising: (a) reacting 4-oxo-1,2-cyclopentanedicarboxylic acid (V) with brucine or (1R,2S)-()-ephedrine, thus preparing the bis-brucine or bis-(1R,2S)-()-ephedrine salt of (V), and (b) precipitating selectively the bis-brucine or bis-(1R,2S)-()-ephedrine salt of (1R,2R)-4-oxo-1,2-cyclopentanedicarboxylic acid II, while the bis-brucine or bis-(1R,2S)-()-ephedrine salt of [(1S,2S)-4-oxo-1,2-cyclopentanedicarboxylic acid stays in solution; (c) liberating the acid II by removal of brucine or (1R,2S)-()-ephedrine from the precipitated salt obtained in step (b).

INJECTABLE TOUGH AND VISCOELASTIC BTA HYDROGEL

The invention describes benzene-1,3,5-tricarboxamide (BTA) based hydrogels. The hydrogels have purpose in tissue culturing for in vitro applications such as drug screening or in vivo applications such as transplantation. The hydrogels are particularly tough but still allow 3D printing and cell culturing. The invention further describes 3D printing of the hydrogels and uses of the hydrogels.

INJECTABLE TOUGH AND VISCOELASTIC BTA HYDROGEL

The invention describes benzene-1,3,5-tricarboxamide (BTA) based hydrogels. The hydrogels have purpose in tissue culturing for in vitro applications such as drug screening or in vivo applications such as transplantation. The hydrogels are particularly tough but still allow 3D printing and cell culturing. The invention further describes 3D printing of the hydrogels and uses of the hydrogels.

Process for the synthesis of carboxylic acid derivatives

The present invention discloses one-pot synthesis of various carboxylic acid derivatives using copper catalyst and sodium cyanide as the cyanide source for bringing in carbonylative coupling in a single step.