Lonza Inc.

Hans P Mettler

Felix Previdoli

Lester Mills

Gareth J Griffiths

Gary Ryan

Francois Moulin

Heinz Wyss

4-Amino-2-chloro-5-cyano-6-(methylthio)primidine is produced from dicyanoketene dimethyl thioacetal and cyanamide by condensation in the presence of a base and subsequent cyclization in the presence of hydrochloric acid. The dicyanoketenedimeth thioacetal is available by reaction of malononitrile, with carbon disulfide and a base and subsequent methylation with dimethyl sulfate. The reaction sequence yields the pyrimidine derivative in good yield and practically free of by-products.

Process for the production of

A new process is described for the production of 1-(aminomethyl)cyclohexane acetic acid, a pharmaceutical agent used as an anticonvulsant. For this purpose a (1-cyanocyclohexyl)malonic acid dialkyl ester is decarbalkoxylated to the corresponding (1-cyanocyclohexyl)acetic acid alkyl ester, then transesterified with a benzyl alcohol and finally hydrogenated to form the end product.

Process for the production of 1-(aminomethyl)cyclohexane acetic acid

A new process is described for the production of 1-(aminomethyl)cyclohexane acetic acid, a pharmaceutical agent used as an anticonvulsant. For this purpose a (1-cyanocyclohexyl)-malonic acid dialkyl ester is decarbalkoxylated to the corresponding (1-cyanocyclohexyl)acetic acid alkyl ester, then transesterified with a benzyl alcohol and finally hydrogenated to form the end product.

Process for the production of 1-(aminomethyl) cyclohexane acetic acid

A new process is described for the production of 1-(aminomethyl) cyclohexane acetic acid, a pharmaceutical agent used as an anticonvulsant. For this purpose a (1-cyanocyclohexyl)malonic acid dialkyl ester is decarbalkoxylated to the corresponding (1-cyanocyclohexyl) acetic acid alkyl ester, then transesterified with a benzyl alcohol and finally hydrogenated to form the end product.

A large-scale industrial process for the production of aminocyanoacetamide is disclosed. A starting material is cyanoacetic acid ester, which is treated with a nitrous acid in a first step to a corresponding hydroxy-iminocyanoacetic acid ester. The hydroxy-iminocyanoacetic acid ester is then hydrogenated and, in a following step, treated with ammonia for obtaining the final product aminocyanoacetamide.

Method for the production of aminocyanoacetamide

A new method for the production of O-substituted hydroxylamines is disclosed. Hydroxylamine-O-sulfonic acid is reacted with alkali alkoxide in the presence of a polar aprotic solvent.

Method for the production of O-substituted hydroxylamines

Process for the production of 2,4-diamino-6-piperidinylpyridine-3-N-oxide starting from hydroxylamine and cyanamide by way of intermediate product 2,4-diamino-6-hydroxypyrimidine-3-N-oxide.

2-Aza-4-(alkoxycarbonyl)spiro[4,5]-decan-3-one and a process for the production of it, starting either from cyclohexylidene malonic acid esters or cyclohexylidene cyanoalkylates. Process of using the product for the production of 1-(aminomethyl)cyclohexane acetic acid.

2-aza-4-(alkoxycarbonyl)spiro[4,5]-decan-3-one

2-Aza-4-(alkoxycarbonyl)spiro[4,5]-decan-3-one and a process for the production of it, starting either from cyclohexylidene malonic acid esters or cyclohexylidene cyanoalkylates. The cyclohexylidene malonic acid ester is reacted with hydrocyanic acid in the presence of a catalytic amount of alkali cyanide or with a stoichiometric amount of alkali cyanide, in an alcohol, and subsequently treated with an acid. The resultant (1-cyanocyclohexyl) malonic acid dialkyl ester is converted by catalytic hydrogenation into the product. The cyclohexylidene cyanoalkylate is reacted with a stoichiometric amount of alkali cyanide, in an alcohol or with hydrocyanic acid in the presence of a catalytic amount of an alkali cyanide. The resultant (1-cyanocyclohexyl)-cyanoacetic acid alkyl ester is reacted in an alcohol in an acid to provide (1-cyanocyclohexyl) malonic acid dialkyl ester. The later ester is converted by catalytic hydrogenation into the product. Process of using the product for the production of 1-(aminomethyl)cyclohexane acetic acid by converting the product with HCl or sulfuric acid at an elevated temperature.

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Brig-Glis, Switzerland

Hans P Mettler