The present invention provides a system for evaporating a radioactive fluid, a method for the synthesis of a radiolabelled compound including this system, and a cassette for the synthesis of a radiolabelled compound comprising this system. The present invention provides advantages over known methods for evaporation of a radioactive fluid as it reduces drastically the amount of radioactive gaseous chemicals that are released in the hot cell. It is gentler and more secure compared to the known process and provides access to radiosyntheic processes that may not been acceptable for safety reasons related to release of volatile radioactive gases during evaporation. In addition, the process yields are higher because the radioactive volatiles are labelled intermediate species.

This invention relates to a method for producing an alkenyl 1-aminocyclopropane-1-carboxylic acid of Formula I wherein R.sup.1 is a protecting group, n is an integer between 1 and 10, and A and B are chiral centres such that when A is S, B is R and when A is R, B is S. The method comprises a stereoselective formation of the cyclopropane moiety by cycloaddition onto a double bond, in a molecule comprising a chiral template, Formula lc. Further provided is the use of Formula I in the production of stapled peptides. ##STR00001##

This invention relates to a method for producing an alkenyl 1-aminocyclopropane-1-carboxylic acid of Formula I wherein R.sup.1 is a protecting group, n is an integer between 1 and 10, and A and B are chiral centres such that when A is S, B is R and when A is R, B is S. The method comprises a stereoselective formation of the cyclopropane moiety by cycloaddition onto a double bond, in a molecule comprising a chiral template, Formula lc. Further provided is the use of Formula I in the production of stapled peptides. ##STR00001##

Disclosed are cyclopentene compounds for use as inhibitors of aminotransferases such as gamma-aminobutyric acid (GABA) aminotransferase (AT) and/or ornithine aminotransferase (OAT). The disclosed cyclopentene compounds include 3-amino-4-halocyclopente carboxylic acid compounds which may be formulated in pharmaceutical composition for treating diseases and disorders associated with GABA-AT and/or OAT activity, including epilepsy, addiction, hepatocellular carcinoma (HCC), and non-small cell lung cancer (NSCLC).

In the process of the present invention, cariprazine is prepared by converting (trans-4-amino-cyclohexyl)-acetic acid ethyl ester hydrochloride to trans-4-aminocyclohexyl) acetic acid or its hydrochloride by hydrolysis, from the obtained product with addition of dimethylcarbamoyl derivative as a suitable reagent (trans-4-{[(dimethylamino)carbonyl]amino}cyclohexyl) acetic acid is formed, then the obtained compound is linked to 1-{2,3-dichlorophenyl)˜piperazine in the presence of carboxylic acid activating coupling reagent, and so 1,1-dimethyl-3-[trans-4-(2-oxo-2-(4-(2,3-dichlorophenyl)piperazin-1-yl-ethyl)cyclohexyl] urea is formed, which is converted to cariprazine borane adduct of formula (2) in the presence of reducing agent, and finally the product itself is eliminated directly or is obtained from its salt by a known method. The invention also relates to a group of intermediate compounds that are formed and/or used in the process according to the present invention.

In the process of the present invention, cariprazine is prepared by converting (trans-4-amino-cyclohexyl)-acetic acid ethyl ester hydrochloride to trans-4-aminocyclohexyl) acetic acid or its hydrochloride by hydrolysis, from the obtained product with addition of dimethylcarbamoyl derivative as a suitable reagent (trans-4-{[(dimethylamino)carbonyl]amino}cyclohexyl) acetic acid is formed, then the obtained compound is linked to 1-{2,3-dichlorophenyl)˜piperazine in the presence of carboxylic acid activating coupling reagent, and so 1,1-dimethyl-3-[trans-4-(2-oxo-2-(4-(2,3-dichlorophenyl)piperazin-1-yl-ethyl)cyclohexyl] urea is formed, which is converted to cariprazine borane adduct of formula (2) in the presence of reducing agent, and finally the product itself is eliminated directly or is obtained from its salt by a known method. The invention also relates to a group of intermediate compounds that are formed and/or used in the process according to the present invention.

1-Aminocyclopropanecarboxylic acid non-hydrate can be obtained by treating 1-aminocyclopropanecarboxylic acid hydrochloride with a tertiary amine in the presence of a C.sub.3-C.sub.4 alcohol and water, keeping the reaction mixture at 50° C. or below, collecting the precipitated crystal of 1-aminocyclopropanecarboxylic acid 0.5 hydrate by filtration, and contacting the obtained crystal with a C.sub.1-C.sub.2 alcohol.

1-Aminocyclopropanecarboxylic acid non-hydrate can be obtained by treating 1-aminocyclopropanecarboxylic acid hydrochloride with a tertiary amine in the presence of a C.sub.3-C.sub.4 alcohol and water, keeping the reaction mixture at 50° C. or below, collecting the precipitated crystal of 1-aminocyclopropanecarboxylic acid 0.5 hydrate by filtration, and contacting the obtained crystal with a C.sub.1-C.sub.2 alcohol.

1-Aminocyclopropanecarboxylic acid non-hydrate can be obtained by treating 1-aminocyclopropanecarboxylic acid hydrochloride with a tertiary amine in the presence of a C.sub.3-C.sub.4 alcohol and water, keeping the reaction mixture at 50° C. or below, collecting the precipitated crystal of 1-aminocyclopropanecarboxylic acid 0.5 hydrate by filtration, and contacting the obtained crystal with a C.sub.1-C.sub.2 alcohol.

1-Aminocyclopropanecarboxylic acid non-hydrate can be obtained by treating 1-aminocyclopropanecarboxylic acid hydrochloride with a tertiary amine in the presence of a C.sub.3-C.sub.4 alcohol and water, keeping the reaction mixture at 50° C. or below, collecting the precipitated crystal of 1-aminocyclopropanecarboxylic acid 0.5 hydrate by filtration, and contacting the obtained crystal with a C.sub.1-C.sub.2 alcohol.