- Expedient synthesis of mequitazine an antihistaminic drug by palladium catalyzed allylic alkylation of sodium phenothiazinate
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A short and straightforward synthesis of the antihistaminic drug mequitazine is reported, based on an efficient palladium catalyzed allylic alkylation of 1-aza-bicyclo[2.2.2]oct-2-en-3-ylmethyl acetate using sodium phenothiazinate in mild conditions.
- Gonnot, Vanessa,Nicolas, Marc,Mioskowski, Charles,Baati, Rachid
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- Method for industrially producing mequitazine
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The invention relates to a method for industrially producing mequitazine. The method comprises the steps that under the nitrogen condition, trifluoroacetic acid and triethyl silicane are mixed, (E)-10-(1-aza bicyclic[2,2,2]cyn-3-methylene)-phenothiazine is added in batches for a reaction, water and alkali are added in sequence, extraction is performed, and an organic phase is acidified, crystallized and filtered. The method is mild in reaction condition, no high temperature or high energy dissipation is caused, solvents can be recycled, the cost is reduced, and discharge of waste is reduced.
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Paragraph 0027; 0033; 0036-0037
(2019/10/01)
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- NOVEL QUINUCLIDINE DERIVATIVE USEFUL IN THE PREPARATION OF MEQUITAZINE
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The invention relates to a 1-aza-bicyclo[2.2.2]oct-2-en-3-ylmethyl acetate of the formula (I), wherein said compound is useful as a synthesis intermediate for the production of mequitazine.
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Page/Page column 3
(2010/05/13)
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- Highly pure phenothiazine compound, production method thereof, production method of intermediate therefor, and hydrate and novel crystal as starting materials for the intermediate
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According to the method of the present invention, an alkali metal compound, dimethyl sulfoxide, trimethyloxosulfonium halide and 3-quinuclidinone are added in a specific order to give the following compound [II]. This compound is, without treatment or isolation, directly reacted with an alkali metal salt of phenothiazine to give the following compound [III], from which the following compound [I] is obtained. During the production of compound [I], a by-produced acidic gas is removed and water is added to ensure industrial, safe and efficient production of compound [I] at a constantly high yield. Inasmuch as the present invention enables production of the following highly pure compound [A] by eliminating hydrogen halide of compound [I] in glyme in the presence of at least one kind of a base selected from potassium hydroxide and potassium alkoxide, compound [A] having a high purity of not less than 85 mol % can be provided.
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- Phenothiazine derivative
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Phenothiazine derivatives are described of the formula SPC1 In which X1 and X2, which may be the same or different, are H, R, F, Cl, Br, OR, CN, --COR, CH3, --S--R, --SOR, --SO2 R or --SO2 N(CH3)2, where R is an alkyl group having from 1 to 4 carbon atoms, and the quinuclidine ring is substituted by the group --(CH2)x -- in the 2- or 3- position, x being 1 or 2 when said group is substituted in the 2-position and being 0 or 1 when said group is substituted in the 3-position (because of electronic hindrance), and their acid addition and quaternary ammonium salts, have valuable pharmacological properties. In particular, these compounds have anti-histaminic, anti-cholinergic, adrenolytic, neuro-sedative, tranquillizing and/or spasmolytic properties. These compounds are prepared by condensing an appropriate phenothiazine with a quinuclidine derivative of the formula SPC2 In which x has the above-stated meaning and Z is a halogen atom or a reactive ester group.
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