Abstract

Disclosed in the present invention are a fluralaner intermediate and a method for preparing fluralaner thereby. The fluralaner intermediate-5 is aaa. A synthetic route comprises: using m-xylene as a starting raw material, performing halogenation and oxidation reactions to obtain bbb, and then further performing oximation, cyanation, and hydrolysis reactions, or performing cyanation, oximation, and hydrolysis reactions to obtain the intermediate-5. According to some examples of the present invention, although the synthesis route is expanded to comprise five steps from two steps in the prior art, a relatively high total yield is unexpectedly obtained, and the purity of the intermediate-5 is also greatly improved. Meanwhile, an initiator for preparing the intermediate-5 is adjusted from expensive 4-bromo-2-methylbenzoic acid to low-price m-xylene, such that the cost of the intermediate-5 is greatly reduced, and the market competitiveness of fluralaner is improved to the greatest extent and in a real sense; meanwhile, the reaction conditions are mild, the synthesis difficulty is low, and the method is more environment-friendly.

IPC Classes  ?

• C07C 17/12 - Preparation of halogenated hydrocarbons by replacement by halogens of hydrogen atoms in the ring of aromatic compounds
• C07C 25/125 - Halogenated xylenes
• C07C 45/28 - Preparation of compounds having C=O groups bound only to carbon or hydrogen atomsPreparation of chelates of such compounds by oxidation of —CHx-moieties
• C07C 47/55 - Compounds having —CHO groups bound to carbon atoms of six-membered aromatic rings containing halogen
• C07C 249/08 - Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes by reaction of hydroxylamines with carbonyl compounds
• C07C 251/48 - Oximes with oxygen atoms of oxyimino groups bound to hydrogen atoms or to carbon atoms of unsubstituted hydrocarbon radicals with the carbon atom of at least one of the oxyimino groups bound to a carbon atom of a six-membered aromatic ring
• C07C 249/12 - Preparation of compounds containing nitrogen atoms doubly-bound to a carbon skeleton of oximes by reactions not involving the formation of oxyimino groups
• C07C 253/14 - Preparation of carboxylic acid nitriles by reaction of cyanides with halogen-containing compounds with replacement of halogen atoms by cyano groups
• C07C 255/64 - Carboxylic acid nitriles containing cyano groups and nitrogen atoms further bound to other hetero atoms, other than oxygen atoms of nitro or nitroso groups, bound to the same carbon skeleton with the nitrogen atoms further bound to oxygen atoms
• C07D 261/04 - Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member

Abstract

The present disclosure discloses a method for safely preparing pimavanserin and tartrate thereof by using triphosgene. The synthesis route includes: Raw materials used in the method of the present disclosure are safe and inexpensive, thereby effectively reducing the production costs. The method of the present disclosure has mild reaction conditions, and avoids using phosgene, which is highly toxic and difficult to handle is avoided. Thus, the method is readily implemented industrially.

IPC Classes  ?

• C07D 211/98 - Nitrogen atom

Abstract

Disclosed in the present invention is a method for safely preparing pimavanserin and a tartrate salt thereof using triphosgene. The synthesis routes comprise (1), (2), (3), (4) and (5). The raw materials used in the method of the present invention are safe, and have low cost, effectively reducing the production cost. The reaction conditions of the method of the present invention are mild, the use of phosgene, having high toxicity and being difficult to operate, can be avoided, and the method is easy to implement industrially.

IPC Classes  ?

• C07D 211/58 - Nitrogen atoms attached in position 4
• C07C 213/02 - Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
• C07C 217/58 - Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups bound to carbon atoms of at least one six-membered aromatic ring and amino groups bound to acyclic carbon atoms or to carbon atoms of rings other than six-membered aromatic rings of the same carbon skeleton with amino groups linked to the six-membered aromatic ring, or to the condensed ring system containing that ring, by carbon chains not further substituted by singly-bound oxygen atoms with amino groups and the six-membered aromatic ring, or the condensed ring system containing that ring, bound to the same carbon atom of the carbon chain
• C07C 59/255 - Tartaric acid
• C07C 51/41 - Preparation of salts of carboxylic acids by conversion of the acids or their salts into salts with the same carboxylic acid part