43 results about "Sarpogrelate Hydrochloride" patented technology

The invention provides a preparation method of high-purity sarpogrelate hydrochloride. The method comprises the following steps of: carrying out alkali dissociation on 1-dimethylamino-3-[2-[2-(3-methoxyphenyl)ethyl]phenoxy-2-propanol hydrochloride which is taken as a raw material, reacting the dissociated 1-dimethylamino-3-[2-[2-(3-methoxyphenyl)ethyl]phenoxy-2-propanol hydrochloride with succinic anhydride to obtain an ester, acidifying the ester to obtain a sarpogrelate hydrochloride crude product, and purifying the sarpogrelate hydrochloride crude product by using butanone as a recrystallization solvent to obtain the sarpogrelate hydrochloride, wherein the purity of the obtained sarpogrelate hydrochloride is higher than 9.9%, the any individual impurity of the obtained sarpogrelate hydrochloride is less than 0.1%, and the yield of the obtained sarpogrelate hydrochloride is higher than 90%. The preparation method adopts the single solvent for recrystallization, which facilitates solvent recovery, so that the preparation method is suitable for industrial production.

Provided is a preparing method of sarpogrelate hydrochloride, characterized in that 2-((3-methoxyl)styrylcoumarin)phenol mixture containing triphenylphosphine oxide is catalyzed and hydrogenated, and then reacted with epichlorohydrin and dimethylamine to obtain 2-(dimethylamino)-1-(o-(m-methoxyphenylethyl)phenoxymethyl)ethanol, at the same time, triphenylphosphine oxide is separated or not, reacted with succinic anhydride, salt-formed with chlorine hydride, and re-crystallization by a proper solvent, so as to obtain sarpogrelate hydrochloride.

The invention discloses a synthetic method of a sarpogrelate intermediate 2-[2-(3-methoxyphenyl)ethyl]phenol and relates to the technical field of organic synthesis. In the method, with m-methoxyl chlorobenzene, which is easy to obtain and is low in cost, as a raw material, the method includes the steps of: 1) performing condensation to the raw material with triethyl phosphite; and 2) performing condensation with o-phenylmethoxyl benzaldehyde (which is prepared from salicylic acid and chlorobenzene), performing hydrogenation to alkylate a double bond, and crystallizing a product with petroleum ether to prepare a white crystal target product. The method simplifies process steps, reduces loss ratio and is 99.5% in product purity. The 2-[2-(3-methoxyphenyl)ethyl]phenol is used for preparing sarpogrelate hydrochloride, wherein single impurity is less than 0.1% in content and the product purity reaches more than 99.8%.

The invention discloses a one-pot method for preparing sarpogrelate hydrochloride photodegradation impurities I, II, III and IV. The method comprises the steps as follows: S1, photodegradation: 2-4 mg / mL of a solution is prepared by dissolving sarpogrelate hydrochloride in water, is treated at the high temperature of 80-90 DEG C for 1-2 h and then sequentially irradiated by a 1200,000-lux cold white fluorescent lamp for 4-6 h and a 200 Wh / m<2> ultraviolet fluorescent lamp for 3-5 h, finally, the degraded solution is concentrated and frozen to dryness, and a degraded mixture is obtained; S2, high-speed countercurrent chromatography: the degraded mixture is dissolved with a fixed phase and a mobile phase with the same volume to serve as a sample solution, ethyl acetate-ethanol-water-formic acid (4:1:5:0.025, v / v / v / v) serves as a two-phase solvent system, the upper phase is the fixed phase, the lower phase is the mobile phase, and the impurities I, II, III and IV are prepared through one-time separation under the conditions that the main engine rotational speed is 800 r / min, the flow velocity is 2.0 mL / min and the detection wavelength is 272 nm. The method adopts few steps and has high efficiency.

The invention belongs to the technical field of organic synthesis of medicines, and particularly relates to a synthetic method of sarpogrelate hydrochloride intermediate 2-(3-dimethylamino-2-hydroxyl) propoxy benzaldehyde, which comprises the following steps: by taking salicylaldehyde as a raw material, carrying out etherification reaction on the salicylaldehyde and epoxy chloropropane in the presence of an acid-binding agent to generate intermediate 2-(oxirane-2-methoxy) benzaldehyde; carrying out amination reaction on the 2-(3-dimethylamino-2-hydroxy) propoxy benzaldehyde and dimethylamine to generate 2-(3-dimethylamino-2-hydroxy) propoxy benzaldehyde; the epichlorohydrin is used as a reaction solvent at the same time; no additional reaction solvent is added in the etherification reaction and the amination reaction. The 2-(3-dimethylamino-2-hydroxyl) propoxybenzaldehyde is prepared from salicylaldehyde through two-step reaction, no additional reaction solvent is added, the cost of the reaction solvent is reduced, and meanwhile, environmental pollution caused by direct discharge of the reaction solvent or energy consumption input increased by recovery of the reaction solvent is avoided.

The invention relates to a sarpogrelate hydrochloride lipidosome solid preparation and a preparation method thereof. The preparation method comprises the following steps: selecting sarpogrelate hydrochloride, dilauroyl phosphatidylcholine, phosphatidyl ethanolamine, phosphatidyl glycerol and cholesterol with specific weight ratio to prepare sarpogrelate hydrochloride lipidosome with excellent quality; and preparing the solid preparation by the common preparation method. Compared with the conventional preparation, the preparation provided by the invention improves the stability, the bioavailability and the product quality of the preparation and reduces the toxic or side effect.

The invention provides a sarpogrelate intermediate and a preparation method thereof. The sarpogrelate intermediate is a compound shown as formula VI. The preparation method of the intermediate comprises a Grignard reaction of salicylic aldehyde with phenolic groups protected and a Grignard reagent. The method is mild in reaction conditions, low in energy consumption and small in pollutions, and has relatively high conversion rate and low cost of the raw materials. The obtained sarpogrelate hydrochloride has high purity with the detection purity of HPLC higher than 99%. The method is suitable for large-scale production conversion.