The Optimization Of Synthesizing Process Of Dutasteride And Synthesis Of Its Derivatives

As the second generation of5α-reductase inhibitors, dutasteride is a kind of drug forthe treatment of benign prostatic hyperplasia (BPH) by Britain’s Glaxosmithkline(GSK) pharmaceutical company. In the early2003the United States and the EuropeanUnion have been listed. Approval for its import in China in2011, commodity calledAvodart, the main form of dutasteride is soft capsule (0.5mg/grain).In the experiment of dutasteride synthesis, we have done lots experiments to getqualified products.But in the amplification experiments, the disadvantages of currentprocess have also been gradually revealed. The third step in the synthesis ofdutasteride catalytic hydrogenation. First of all,the capability of Pd/C catalyst is hardto separate from the product, also the use of hydrogen5Mpa make the step risk isbigger, so that not good for the industrial production.We have done lots of experiment for the improve of the third step.At last themethod done as followed: at room temperature a certain concentration of NaBH3CNsolution drops slowly into D-2dissolve in organic solvents for reduction reactionproducts. The production rate is not lower than Pd/C catalytic hydrogenation method.At the same time the final products dutasteride API is also available degrees purityabove99.8%, other relevant material content below0.1%.It not only ensuring degreeAPI quality on the basis of dutasteride,but also operation more safe and convenient.According to the molecular structure of dutasteride, the double bond of the1,2oxidation to have dutasteride derivatives. After the double bond of1,2reduction,wehave reduction on the carbonyl group of3, make lactam key reduction in circularsecondary amine, connect the acyl chloride into amide bond to have dutasteridederivatives.