Method for synthesizing lorlatinib

• Main Authors: SHA YU, CHEN JIAQI, JIANG QINGQIAN, ZHAO QINGMENG, GUO AOFENG, SUN WEIQUAN
• Format: Patent
• Language: Chinese; English
• Published: 18.01.2019
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; METALLURGY; ORGANIC CHEMISTRY

The invention belongs to the technical field of medicines, and relates to a method for synthesizing lorlatinib (PF-06463922), which is finally synthesized from 5-fluoro-3-methyl isobenzofuran-1(3H)-ketone and 1-methyl-3-((methylamino)methyl)-1H-pyrazol-5-nitrile through the reacting steps including aminolysis, substitution, coupling, chiral resolution and the like, or from (S)-5-fluoro-3-methyl isobenzofuran-1(3H)-ketone and 1-methyl-3-((methylamino)methyl)-1H-pyrazol-5-nitrile through the reacting steps including aminolysis, substitution, coupling and the like. According to the method, a novel method is provided to synthesis of an anti-tumor medicine lorlatinib (PF-06463922). 本发明属于医药技术领域，涉及劳拉替尼(PF-06463922)的合成方法，即5-氟-3-甲基异苯并呋喃-1(3H)-酮与1-甲基-3-((甲氨基)甲基)-1H-吡唑-5-腈经过氨解、取代、偶联、手性拆分等反应步骤最终合成劳拉替尼(PF-06463922)，或者(S)-5-氟-3-甲基异苯并呋喃-1(3H)-酮与1-甲基-3-((甲氨基)甲基)-1H-吡唑-5-腈经过氨解、取代、偶联等反应步骤最终合称成劳拉替尼(PF-06463922),为抗肿瘤药物劳拉替尼(PF-06463922)的合成提供了新的方法。