Siegfried Aktiengesellschaft

Contraf-Nicotex-Tobacco Gmbh

Siegfried (Nantong) Pharmaceuticals Co. Ltd.

Ben Pan

Beat Theodor Weber

Jiang Chen

Bernhard Berger

Christian Lothschütz

Christian LOTHSCHÜTZ

The present invention relates to a method of preparing racemic nicotine comprising: (i) reacting ethyl nicotinate and N-vinylpyrrolidone in the presence of an alcoholate base to 3-nicotinoyl-1-vinylpyrrolidin-2-one; (ii) reacting the 3-nicotinoyl-1-vinylpyrrolidin-2-one with an acid to myosmine; (iii) reducing the myosmine to nornicotine using a reducing agent; and (iv) methylating the nornicotine to obtain the racemic nicotine.

Preparation of racemic nicotine by reaction of ethyl nicotinate with N-vinylpyrrolidone in the presence of an alcoholate base and subsequent process steps

The present invention relates to a method of separating racemic nicotine of Formula (1-a) as a mixture of the (R)- and (S)-enantiomers into the enantiomerically pure (S)- and (R)-nicotine represented by Formula (1-b) and (1-c), by adding a mixture of the L- and the D-enantiomer of a O,O'-disubstituted tartaric acid, wherein the molar ratio of the L- to the D-enantiomer is from 80:20 to 95:5, and obtaining the (S)-nicotine of formula (1-b), or by adding O,O&#x2032;-dibenzoyl-D-tartaric acid and obtaining the (R)-nicotine of formula (1-c). 

Enantiomeric separation of racemic nicotine by addition of an O,O&#x2033;-disubstituted tartaric acid enantiomer

The present invention discloses a method of manufacturing 4-chloro-7H-pyrrolo[2,3-d]pyrimidine comprising the steps: a) Preparing ethyl 2-cyano-4,4-dimethoxybutanoate by coupling ethyl 2-cyanoacetate and 2-bromo-1,1-dimethoxyethane; b) Preparing 6-amino-5-(2,2-dimethoxyethyl)pyrimidin-4-ol by adding formamidine to ethyl 2-cyano-4,4-dimethoxybutanoate; c) Converting 6-amino-5-(2,2-dimethoxyethyl)pyrimidin-4-ol to 7H-pyrrolo[2,3-d]pyrimidin-4-ol; and d) Converting the 7H-pyrrolo[2,3-d]pyrimidin-4-ol to 4-chloro-7H-pyrrolo[2,3-d]pyrimidine. The method offers increased yield, less by-products and a decrease in waste compared to methods known as being state of the art.

Method of manufacturing 4-chloro-7H-pyrrolo[2,3-D]pyrimidine

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Nantong, China

Ben Pan