Tetrahydrobenzothiazole derivative and preparation method thereof

Abstract

The invention discloses a tetrahydrobenzothiazole derivate for treating nerve diseases. Particularly, the tetrahydrobenzothiazole derivate comprises compounds shown in the following formula I: (S)-(-)-2-amino-6-(propionamide)-4,5,6,7- tetrahydrobenzothiazole, acceptable salt of the compounds in pharmacy or solvates of the compounds. The compounds or compositions of the tetrahydrobenzothiazole derivate can be used for treating nervous system diseases.

Description

technical field [0001] The invention relates to a preparation method of tetrahydrobenzothiazole derivatives such as pramipexole and its dihydrochloride monohydrate, and pramipexole dihydrochloride monohydrate obtained by the method. Background technique [0002] Pramipexole is used in early and advanced Parkinson's disease as a dopamine agonist that stimulates dopamine receptors in the brain. In practice, pramipexole dihydrochloride monohydrate is preferred as the compound for treating Parkinson's disease. The chemical name of pramipexole dihydrochloride monohydrate is (S)-(-)-2-amino-6-(propylamino)-4,5,6,7-tetrahydrobenzothiazole dihydrochloride Monohydrate, wherein (S) means that pramipexole hydrochloride is in S configuration, and (-) means that pramipexole hydrochloride is left-handed. It is known that pramipexole hydrochloride with S configuration and left-handedness can be used as a pharmaceutical raw material for preparing a drug for treating Parkinson's disease. ...

AI Technical Summary

Problems solved by technology

J. Med.Chem.1987,30,494-498 discloses a kind of preparation method of pramipexole hydrochloride, this method uses (-) 2-amino-6-propionylamino-4,5,6,7-tetrahydrobenzene And thiazole as raw material, N in THF (tetrahydrofuran) 2 Under protection, react with borane solution of THF to obtain (S)-(-)-2-amino-6-(propylamino)-4,5,6,7-tetrahydrobenzothiazine, and then convert to di Hydrochloride; The specific content of this preparation method is, at room temperature and logical N 2 Under protection, add THF borane solution dropwise to THF containing (-) 2-amino-6-propionylamino-4,5,6,7-tetrahydrobenzothiazole, then stir the reaction at 50°C After 1 hour and cooling, water and concentrated hydrochloric acid were added; THF was evaporated and 25% sodium hydroxide solution was added to the aqueous phase, and then filtered to obtain a precipitate ((S)-(-)-2-amino-6-(propylamino )-4,5,6,7-tetrahydrobenzothiazole), the obtained precipitate was washed with water and dissolved in hot ethyl acetate; the water in the solution was removed (Mg 2 SO 4 ) and concentrated, filtered to obtain a precipitate, washed with ethyl acetate, converted to dihydrochloride and recrystallized from methanol to give (S)-(-)-2-amino-6-(propylamino) -4,5,6,7-tetrahydrobenzothiazole dihydrochloride; the shortcoming of this method is that the borane solution manufacture method of THF is complicated, is not suitable for industrial production, and because borane is colorless and highly toxic, flammable, Explosive, easy to hydrolyze, poor stability, difficult to store and transport, so the reaction safety is low

Chinese patent CN1834092 has improved the above-mentioned method, with NaBH 4 and BF 3 Borane is generated in situ, but the boron trifluoride ether solution decomposes with water, has a pungent smell, and ether is highly flammable, the reaction conditions are harsh and the equipment requirements are very high, and it is not suitable for industrial production

Chinese patent CN101676272 uses sodium borohydride and lithium aluminum hydride as reducing agent for reduction, and the conditions are relatively mild, but it needs to be reacted in a reflux state, and the reaction time is very long. Components are highly corrosive, and are likely to cause running, popping, dripping, and leaking. There is a danger of explosion in tetrahydrofuran in a reflux state, so the requirements for equipment and workshops are very high; and lithium aluminum hydride is expensive and sensitive to water and air. The danger of combustion and explosion; so it is also not easy to carry out industrial production

Chinese patent CN 101585818A discloses a method for preparing an intermediate of pramipexole hydrochloride, the steps are: in a solvent, 2-amino-6-propionylamino-4,5,6,7-tetrahydro Benzothiazole in Zn(BH 4 ) 2 In presence, carry out reduction reaction, and then collect 2-amino-6-propylamino-4,5,6,7-tetrahydrobenzothiazole from the reaction product; this method needs to be carried out under high temperature environment, the boiling point of tetrahydrofuran as solvent Low, flammable and explosive; damage to reaction equipment, high requirements for plant and equipment; and Zn(BH 4 ) 2 Difficult to prepare and difficult to store

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