SYNTHESIS OF CARBAMOYLPYRIDONE HIV INTEGRASE INHIBITORS AND THEIR INTERMEDIATES

• Main Authors: NAGAMATSU HIROKI, JOHNS BRIAN ALVIN, KAWASUJI TAKASHI, YOSHIDA HIROSHI, TAODA YOSHIYUKI
• Format: Patent
• Language: English; Japanese
• Published: 31.03.2016
• Subjects: CHEMISTRY; HETEROCYCLIC COMPOUNDS; HUMAN NECESSITIES; HYGIENE; MEDICAL OR VETERINARY SCIENCE; METALLURGY; ORGANIC CHEMISTRY; PREPARATIONS FOR MEDICAL, DENTAL, OR TOILET PURPOSES

PROBLEM TO BE SOLVED: To provide a method for synthesis of carbamoylpyridone HIV integrase inhibitors.SOLUTION: The present invention provides a method for synthesis of carbamoylpyridone HIV integrase inhibitors, including the steps of obtaining brominated compound II-II by a reaction of the following scheme, and forming 2,4-difluorophenyl CH2-NH-C(O)- side chain for debenzylation [R is -CHO, -CH(OH)2, -CH(OH)(OR4), -CH(OH)-CH2OH or -CH(OR5)(OR6); P1 is H or a hydroxyl protecting group; P3 is H or a carboxy protecting group; R4 is a C1-6 alkyl; R5 and R6 are a C1-6 alkyl or a C1-6 alkyl and together form a 5-, 6- or 7-membered ring].SELECTED DRAWING: None 【課題】カルバモイルピリドンHIVインテグラーゼ阻害剤の合成方法の提供。【解決手段】下記スキームの反応により臭素化化合物II-IIを得る工程、及び、2,4-ジ-フルオロフェニルCH2-NH-C(O)-側鎖を形成し脱ベンジル化する工程、を含むカルバモイルピリドンHIVインテグラーゼ阻害剤の合成方法。[Rは-CHO、-CH(OH)2、-CH(OH)(OR4)、-CH(OH)-CH2OH又は-CH(OR5)(OR6)；P1はH又はヒドロキシル保護基；P3は、H又はカルボキシ保護基；R4は、C1-6アルキル；R5及びR6は、C1-6アルキル、又はC1-6アルキルであり一緒になって5-、6-又は7-員環を形成]【選択図】なし