The present disclosure provides processes for the synthesis of organic compounds, in particular processes for the synthesis of heteroaryl-substituted sulfur(VI) compounds by nucleophilic aromatic substitution.

The present disclosure provides processes for the synthesis of organic compounds, in particular processes for the synthesis of heteroaryl-substituted sulfur(VI) compounds by nucleophilic aromatic substitution.

The invention provides methods of chemical synthesis of the pharmacological agent 2-[4-[(2,3,4-trimethoxyphenyl)methyl]piperazin-1-yl]ethyl pyridine-3-carboxylate, also called CV-8972. The methods entail formation of a free base form of 2-[4-[(2,3,4-trimethoxyphenyl)methyl]piperazin-1-yl]ethanol, also called CV-8814, as intermediate without producing a salt form of CV-8814.

The invention provides methods of chemical synthesis of the pharmacological agent 2-[4-[(2,3,4-trimethoxyphenyl)methyl]piperazin-1-yl]ethyl pyridine-3-carboxylate, also called CV-8972. The methods entail formation of a free base form of 2-[4-[(2,3,4-trimethoxyphenyl)methyl]piperazin-1-yl]ethanol, also called CV-8814, as intermediate without producing a salt form of CV-8814.

The present invention relates to a method for preparing substituted 4-aminoindane derivatives from 2-(hydroxyalkyl)-anilines by cyclization,

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in which the substituents R.sup.1, R.sup.2, R.sup.3 and R.sup.4 have the definitions as specified in the description.

Disclosed are processes for preparing [(3-hydroxypyridine-2-carbonyl)amino]-alkanoic acids, derivatives, inter alia, 5-aryl substituted and 5-heteroaryl substituted [(3-hydroxypyridine-2-carbonyl]amino}acetic acids. Further disclosed are methods for making prodrugs of [(3-hydroxypyridine-2-carbonyl)-amino]acetic acids, for example, [(3-hydroxypyridine-2-carbonyl]amino}acetic acid esters and {[3-hydroxypyridine-2-carbonyl]amino}acetic acid amides. The disclosed compounds are useful as prolyl hydroxylase inhibitors or for treating conditions wherein prolyl hydroxylase inhibition is desired.

Disclosed are processes for preparing [(3-hydroxypyridine-2-carbonyl)amino]-alkanoic acids, derivatives, inter alia, 5-aryl substituted and 5-heteroaryl substituted [(3-hydroxypyridine-2-carbonyl]amino}acetic acids. Further disclosed are methods for making prodrugs of [(3-hydroxypyridine-2-carbonyl)-amino]acetic acids, for example, [(3-hydroxypyridine-2-carbonyl]amino}acetic acid esters and {[3-hydroxypyridine-2-carbonyl]amino}acetic acid amides. The disclosed compounds are useful as prolyl hydroxylase inhibitors or for treating conditions wherein prolyl hydroxylase inhibition is desired.

A process for preparing a polyfluorinated compound of formula Ar—R.sub.1 (I), wherein Ar—R.sub.1 (I) is an aromatic ring system

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wherein R.sub.1 is selected from the group consisting of SF.sub.4Cl, SF.sub.3, SF.sub.2CF.sub.3, TeF.sub.5, TeF.sub.4CF.sub.3, SeF.sub.3, IF.sub.2, SeF.sub.2CF.sub.3, and IF.sub.4, X.sub.2 is N or CR.sub.2, X.sub.3 is N or CR.sub.3, X.sub.4 is N or CR.sub.4, X.sub.5 is N or CR.sub.5, X.sub.6 is N or CR.sub.6, and the total number of nitrogen atoms in the aromatic ring system is between 0 and 3, wherein R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are independently selected from the group consisting of hydrogen, fluoro, chloro, bromo, nitro, trifluoromethyl, 2,2,2-trifluoroethyl, pentafluorosulfanyl, phthalimido, azido, benzyloxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, methoxycarbonyl, ethoxycarbonyl, methylcarbonyl, ethylcarbonyl, acetoxy, t-butyl, phenylcarbonyl, benzylcarbonyl, 3-trifluoromethylphenyl, phenylsulfonyl, methylsulfonyl, chlorophenyl, methyldoxolonyl, methyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, fluoromethyl, fluoroethyl and phenyl.

A process for preparing a polyfluorinated compound of formula Ar—R.sub.1 (I), wherein Ar—R.sub.1 (I) is an aromatic ring system

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wherein R.sub.1 is selected from the group consisting of SF.sub.4Cl, SF.sub.3, SF.sub.2CF.sub.3, TeF.sub.5, TeF.sub.4CF.sub.3, SeF.sub.3, IF.sub.2, SeF.sub.2CF.sub.3, and IF.sub.4, X.sub.2 is N or CR.sub.2, X.sub.3 is N or CR.sub.3, X.sub.4 is N or CR.sub.4, X.sub.5 is N or CR.sub.5, X.sub.6 is N or CR.sub.6, and the total number of nitrogen atoms in the aromatic ring system is between 0 and 3, wherein R.sub.2, R.sub.3, R.sub.4, R.sub.5 and R.sub.6 are independently selected from the group consisting of hydrogen, fluoro, chloro, bromo, nitro, trifluoromethyl, 2,2,2-trifluoroethyl, pentafluorosulfanyl, phthalimido, azido, benzyloxy, trifluoromethoxy, 2,2,2-trifluoroethoxy, methoxycarbonyl, ethoxycarbonyl, methylcarbonyl, ethylcarbonyl, acetoxy, t-butyl, phenylcarbonyl, benzylcarbonyl, 3-trifluoromethylphenyl, phenylsulfonyl, methylsulfonyl, chlorophenyl, methyldoxolonyl, methyl, isopropyl, cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, fluoromethyl, fluoroethyl and phenyl.

Disclosed are a nicotinic acid or isonicotinic acid compound and a use thereof. The compound is the compound shown in Formula I, or a pharmaceutically acceptable salt, ester or solvate thereof. Efficacy tests demonstrate that the nicotinic acid compound can inhibit botulinum toxin endopeptidase activity in vitro, and has a significant protective effect on mice poisoned with botulinum toxin. On this basis, the compound may be used to prepare a drug preventing and/or treating botulinum toxin exposure and/or poisoning. ##STR00001##