Lonza Inc.

Felix Previdoli

Hans P Mettler

Gareth J Griffiths

Lester Mills

Rene Imwinkelried

Gary Ryan

Andre Escher

Aleksander Warm

Leander Tenud

Gerhard C Stucky

Francois Moulin

Heinz Wyss

A process for the production of 5-chloroxindole starting from chloronitrobenzene. In this way, in a first step, chloronitrobenzene of the formula: ##STR1## is converted with a chloro acetic acid alkyl ester of the general formula: ##STR2## in the presence of a base to a chloronitrobenzene acetic acid alkyl ester of the general formula: ##STR3## The latter is catalytically hydrogenated in a second step with hydrogen to the corresponding amine of the general formula: ##STR4## The latter is then cyclized in a third step in the presence of an acid to the end product according to the formula: ##STR5##

Process for chloronitroacetic acid esters

A process for the production of 2-halo-4,6-dialkoxypyrimidines of the general formula: ##STR1## starting from a propanediimidate or its salts. In the first stage, a propanediimidate or its salts of the general formula: ##STR2## is/are converted with cyanamide of the formula:

Process for the production of 2-halo-4,6-dialkoxy pyrimidines

.beta.,.gamma.-unsaturated .delta.-lactams, especially 2-azabicyclo[2.2.1]hept-5-en-3-one, are produced by Diels-Alder reaction of 1,3-dienes with sulfonyl cyanides and subsequent hydrolysis. The sulfonyl cyanides were formed in situ from cyanogen chloride and the corresponding sulfinates. By the renewed reaction of the sulfinate formed in the hydrolysis of the Diels-Alder adducts with cyanogen chloride, the sulfonyl cyanides are regenerated and a catalytic cyclic process results. The 2-azabicyclo[2.2.1]hept-5-en-3-one is a starting compound in the synthesis of antiviral nucleoside analogs.

Process for the production of lactams

N-5-protected 2,5-diamino-4,6-dichloropyrimidines of general formula: ##STR1## wherein R is an alkoxy group or a trifluorometyl group, are valuable intermediate products for the production of pharmaceutical agents with antiviral properties. The above-mentioned compounds are produced by cyclization of an N protected amino malonic acid ester with guanidine in the presence of an alkali alcoholate and then chlorination of the resulting N-5-protected 4,6-dihydroxy-2,5-diaminopyrimidine.

N-5-protected 2,5-diamino-4,6-dichloropyrimidines and process for their

Process for the production of 5-chloroxindole

A process for the production of 4,6-dialkoxypyrimidines of the general formula: ##STR1## A propanediimidate of the general formula: ##STR2## is converted with an anhydride of the general formula: ##STR3## to provide the product.

Process for the production of 4,6-dialkoxypyrimidines

A process for the production of 2-substituted 4,6-dialkoxypyrimidines starting from a cyanimidate of the general formula: ##STR1## The cyanimidate is cyclized with a hydrogen halide to a halopyrimidine derivative of general formula: ##STR2## The latter is then converted either with a compound of the formula:

Process for the production of 2-substituted 4,6-dialkoxypyrimidines

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

2-Azabicyclo[2.2.1]hept-5-en-3-one is produced by Diels-Alder reaction of cyclopentadiene and methanesulfonyl cyanide and then hydrolytic cleavage of the methanesulfonyl group.

Process for the production of 2-azabicyclo [2.2.1] hept-5-en-3-one

A process for the production of 1-(N-methanesulfonyl-N-methylaminosulfonyl)-3-(2-pyrimidyl) urea derivatives (MMSPH). In the process, methanesulfonylmethylamine (MMSA) is first converted with chlorosulfonylisocyanata (CSI) into a 1-methanesulfonyl-1-methyl-3- (N-methanesulfonyl-N-methylaminosulfonyl) urea derivative (MMMSH) and then the MMMSH is converted with a 2-aminopyridine into the end product.

A process for the production of 1-(N-methanesulfonyl-N-methylaminosulfonyl)-3-(2-pyrimidyl) urea derivatives (MMSPH). In the process, methanesulfonylmethylamine (MMSA) is first converted with chlorosulfonylisocyanate (CSI) into a 1-methanesulfonyl-1-methyl-3-(N-methanesulfonyl-N-methylaminosulfonyl) urea derivative (MMMSH) and then the MMMSH is converted with a 2-aminopyridine into the end product.

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.

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Brig, Switzerland

Felix Previdoli