A process of converting a carbon-carbon multiple bond to a cyclopropane ring, comprising the addition of a N-alkyl-N-nitroso compound to a mixture of alkene precursor, aqueous base and Pd(II)-catalyst, with the N-alkyl-N-nitroso compound obtained directly from an alkyl amine derivative, NaNO.sub.2 and an acid via phase separation of the N-alkyl-N-nitroso compound from the aqueous phase.

Provided herein are methods and intermediates for making (1R,2R,5R)-5-amino-2-methylcyclohexanol hydrochloride, which are useful for the preparation of compounds useful for the treatment of a disease, disorder, or condition associated with the JNK pathway.

Provided herein are methods and intermediates for making (1R,2R,5R)-5-amino-2-methylcyclohexanol hydrochloride, which are useful for the preparation of compounds useful for the treatment of a disease, disorder, or condition associated with the JNK pathway.

An object of the present invention is to develop a therapeutic agent for an inflammatory disease such as an inflammatory bowel disease or NASH, which therapeutic agent shows less side effects and high effectiveness. The present invention provides a compound represented by Formula (I) or a salt thereof; and a Pin1 inhibitor, a pharmaceutical composition, a therapeutic agent or a prophylactic agent for an inflammatory disease, and a therapeutic agent or a prophylactic agent for colon cancer, containing the compound. ##STR00001##

Provided herein are methods and intermediates for making (1R,2R,5R)-5-amino-2-methylcyclohexanol hydrochloride, which are useful for the preparation of compounds useful for the treatment of a disease, disorder, or condition associated with the JNK pathway.

Provided herein are methods and intermediates for making (1R,2R,5R)-5-amino-2-methylcyclohexanol hydrochloride, which are useful for the preparation of compounds useful for the treatment of a disease, disorder, or condition associated with the JNK pathway.

The present invention relates to a novel and improved process for preparing (3S)-3-(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)-3-cyclopropylpropanoic acid of the formula (I), to the compound of the formula (I) in crystalline form and to their use for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of cardiovascular, cardiopulmonary and cardiorenal disorders.

The present invention relates to a novel and improved process for preparing (3S)-3-(4-chloro-3-{[(2S,3R)-2-(4-chlorophenyl)-4,4,4-trifluoro-3-methylbutanoyl]amino}phenyl)-3-cyclopropylpropanoic acid of the formula (I), to the compound of the formula (I) in crystalline form and to their use for the treatment and/or prevention of diseases, in particular for the treatment and/or prevention of cardiovascular, cardiopulmonary and cardiorenal disorders.

The present invention provides a process for preparing a (1,2-dimethyl-3-methylenecyclopentyl)acetate compound of the following general formula (3), wherein R represents a linear or branched alkyl group having 1 to 4 carbon atoms, the process comprising subjecting a haloacetaldehyde alkyl 2,3-dimethyl-2-cyclopentenyl acetal compound of the following general formula (1), wherein R is as defined above, and Y represents a halogen atom, to a dehydrohalogenation reaction in the presence of a base, followed by a rearrangement reaction to obtain a (1,2-dimethyl-2-cyclopentenyl)acetate compound of the following general formula (2), wherein R is as defined above, and subjecting the (1,2-dimethyl-2-cyclopentenyl)acetate compound (2) to an epoxidation reaction, followed by an isomerization reaction and then a methylenation reaction to obtain the (1,2-dimethyl-3-methylenecyclopentyl)acetate compound of the following general formula (3). The present invention also provides a process for preparing (1,2-dimethyl-3-methylenecyclopentyl)acetaldehyde of the following formula (4), the process comprising the aforesaid process for preparing the (1,2-dimethyl-3-methylenecyclopentyl)acetate compound (3), and converting an alkoxycarbonylmethyl group (i.e., —CH.sub.2C(═O)OR) of the (1,2-dimethyl-3-methylenecyclopentyl)acetate compound (3) to a formylmethyl group (i.e., —CH.sub.2CHO) to obtain (1,2-dimethyl-3-methylenecyclopentyl)acetaldehyde (4). ##STR00001##

The present invention provides a process for preparing a (1,2-dimethyl-3-methylenecyclopentyl)acetate compound of the following general formula (3), wherein R represents a linear or branched alkyl group having 1 to 4 carbon atoms, the process comprising subjecting a haloacetaldehyde alkyl 2,3-dimethyl-2-cyclopentenyl acetal compound of the following general formula (1), wherein R is as defined above, and Y represents a halogen atom, to a dehydrohalogenation reaction in the presence of a base, followed by a rearrangement reaction to obtain a (1,2-dimethyl-2-cyclopentenyl)acetate compound of the following general formula (2), wherein R is as defined above, and subjecting the (1,2-dimethyl-2-cyclopentenyl)acetate compound (2) to an epoxidation reaction, followed by an isomerization reaction and then a methylenation reaction to obtain the (1,2-dimethyl-3-methylenecyclopentyl)acetate compound of the following general formula (3). The present invention also provides a process for preparing (1,2-dimethyl-3-methylenecyclopentyl)acetaldehyde of the following formula (4), the process comprising the aforesaid process for preparing the (1,2-dimethyl-3-methylenecyclopentyl)acetate compound (3), and converting an alkoxycarbonylmethyl group (i.e., —CH.sub.2C(═O)OR) of the (1,2-dimethyl-3-methylenecyclopentyl)acetate compound (3) to a formylmethyl group (i.e., —CH.sub.2CHO) to obtain (1,2-dimethyl-3-methylenecyclopentyl)acetaldehyde (4). ##STR00001##