METHOD FOR PREPARING HIGH-PURITY (R)-9-[2-(PHOSPHONOMETHOXY)PROPYL]ADENINE

• Main Authors: CHO, YOUNG BUM, LEE, JAEHEON, CHANG, YOUNG-KIL, CHOI, WON KYOUNG, PARK, EUNRANG
• Format: Patent
• Language: English; French; Korean
• Published: 07.04.2016
• Subjects: ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAININGELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN,SULFUR, SELENIUM OR TELLURIUM; CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

The present invention relates to a method for preparing high-purity (R)-9-[2-(phosphonomethoxy)propyl]adenine (PMPA). Since (diethoxyphosphoryl)methyl naphthalene-1-sulfonate or (diethoxyphosphoryl)methyl naphthalene-2-sulfonate, which has high purity due to an easy reaction process and fewer impurities generated in the reaction, is used as an intermediate, high-purity PMPA can be prepared. In addition, since the PMPA prepared by the method of the present invention has very high purity, tenofovir diisopropyl and acid adduct salts thereof can be prepared at high purity by using the PMPA, and thus the PMPA is very advantageous in producing high-quality raw material medicines. La présente invention concerne un procédé de préparation de (R)-9-[2-(phosphonométhoxy)propyl]adénine (PMPA) de grande pureté. Étant donné que le naphtalène-1-sulfonate de (diéthoxyphosphoryl)méthyle ou le naphtalène-2-sulfonate de (diéthoxyphosphoryl)méthyle, qui présente une grande pureté grâce à un procédé de réaction facile et à la production d'une quantité plus faible d'impuretés au cours de la réaction, est utilisé comme intermédiaire, de la PMPA de grande pureté peut être préparée. En outre, étant donné que la PMPA préparée selon le procédé de la présente invention possède une très grande pureté, du ténofovir diisopropylique et des sels d'addition d'acide associés peuvent être préparés avec une grande pureté au moyen de la PMPA et, par conséquent, la PMPA permet de produire avantageusement des médicaments servant de matières premières de grande qualité. 본 발명은 고순도의 (R)-9-[2-(포스포노메톡시)프로필]아데닌(PMPA)의 제조방법에 관한 것으로서, 반응 공정이 용이하고 반응 중 불순물 생성이 적어 순도가 높은 (디에톡시포스포릴)메틸 나프탈렌-1-설포네이트 또는 (디에톡시포스포릴)메틸 나프탈렌-2-설포네이트를 중간체로 사용하므로, 순도가 높은 PMPA를 제조할 수 있다. 또한, 본 발명의 방법으로 제조된 PMPA는 순도가 매우 높으므로 이를 사용하면 테노포비어 디소프록실 및 이의 산 부가염을 고순도로 제조할 수 있어 고품질의 원료의약품을 생산하는데 매우 유리하다.