AR085857A1 - Proceso para la preparacion de un inhibidor de hiv integrasa - Google Patents

Proceso para la preparacion de un inhibidor de hiv integrasa

Info

Publication number
AR085857A1
AR085857A1 ARP120101177A ARP120101177A AR085857A1 AR 085857 A1 AR085857 A1 AR 085857A1 AR P120101177 A ARP120101177 A AR P120101177A AR P120101177 A ARP120101177 A AR P120101177A AR 085857 A1 AR085857 A1 AR 085857A1
Authority
AR
Argentina
Prior art keywords
formula
conversion
butyl
tert
aryl
Prior art date
Application number
ARP120101177A
Other languages
English (en)
Original Assignee
Gilead Sciences Inc
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Application filed by Gilead Sciences Inc filed Critical Gilead Sciences Inc
Publication of AR085857A1 publication Critical patent/AR085857A1/es

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D491/00—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00
    • C07D491/02—Heterocyclic compounds containing in the condensed ring system both one or more rings having oxygen atoms as the only ring hetero atoms and one or more rings having nitrogen atoms as the only ring hetero atoms, not provided for by groups C07D451/00 - C07D459/00, C07D463/00, C07D477/00 or C07D489/00 in which the condensed system contains two hetero rings
    • C07D491/06—Peri-condensed systems
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
    • C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
    • C07D215/12—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
    • C07D215/14—Radicals substituted by oxygen atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
    • C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
    • C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D405/00—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom
    • C07D405/02—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings
    • C07D405/04—Heterocyclic compounds containing both one or more hetero rings having oxygen atoms as the only ring hetero atoms, and one or more rings having nitrogen as the only ring hetero atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D417/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00
    • C07D417/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings
    • C07D417/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and sulfur atoms as the only ring hetero atoms, not provided for by group C07D415/00 containing two hetero rings directly linked by a ring-member-to-ring-member bond

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Quinoline Compounds (AREA)
  • Nitrogen Condensed Heterocyclic Rings (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

Abstract

Es de utilidad en el tratamiento de infección de HIV.Reivindicación 1: Un proceso para preparar el compuesto de fórmula (1) o una de sus sales, de acuerdo con el esquema general [1], en donde Y es l, Br o Cl; en donde el proceso comprende: acoplamiento de haluro de arilo de fórmula (E1) en condiciones de acoplamiento de Suzuki diastereoselectivas en presencia de un ligando monofosforoso de biarilo quiral que tiene la fórmula (2), en donde R = R’ = H; R’’ = ter-butilo; o R = OMe; R’ = H; R’’ = ter-butilo; o R = N(Me)2; R’ = H; R’’ = ter-butilo; en combinación con un catalizador o precatalizador de paladio y una base y un ácido borónico o éster de boronato en una mezcla de solventes; conversión del alcohol quiral de fórmula (F1) en éter ter-butílico de fórmula (G1) bajo catálisis con ácido de Brönstedt o de Lewis con una fuente de catión ter-butilo o su equivalente; saponificación del éster de fórmula (G1) al compuesto de fórmula (1) en una mezcla de solventes; y opcionalmente conversión del compuesto de fórmula (1) a una sal de fórmula (1’). Reivindicación 15: Un proceso para preparar un compuesto de la fórmula (3) o una de sus sales, en donde: R4 esta seleccionado del grupo de formulas (4); y R6 y R7 están cada uno seleccionados, de modo independiente, de H, halo y alquilo C1-6; de acuerdo con el esquema general [2], en donde: X es I o Br; Y es Cl cuando X es Br o I, o Y es Br cuando X es I, o Y es I; y R es alquilo C1-6; en donde el proceso comprende: conversión de la 4-hidroxiquinolina de fórmula (A) en fenol de fórmula (B) por medio de una reacción de halogenación regioselectiva en la posición 3 del núcleo de quinolina; conversión del fenol de fórmula (B) en dihaluro de arilo de fórmula (C) a través de la activación del fenol con un reactivo de activación y posterior tratamiento con una fuente de haluro en presencia de una base orgánica; conversión del dihaluro de arilo de fórmula (C) en cetona de fórmula (D) por transformación quimioselectiva del grupo 3-halo en un reactivo metálico de arilo y luego reacción del reactivo metálico de arilo con un ácido carboxílico activado; reducción estereoselectiva de cetona de fórmula (D) en alcohol quiral de fórmula (E) por medio de métodos de reducción de cetonas asimétricas; acoplamiento diastereoselectivo del haluro de arilo de fórmula (E) con R4 en presencia de ligando de fosfina de fórmula (Q) en combinación con un catalizador o precatalizador de paladio, una base y un ácido borónico o éster de boronato en una mezcla de solventes; conversión del alcohol quiral de fórmula (F) en éter ter-butílico de fórmula (G) bajo catálisis con ácido de Brönstedt o de Lewis con una fuente de catión ter-butilo o su equivalente; saponificación del éster de fórmula (G) al inhibidor de fórmula (H) en una mezcla de solventes; y opcionalmente conversión del inhibidor de fórmula (H) en una de sus sales.
ARP120101177A 2011-04-04 2012-04-04 Proceso para la preparacion de un inhibidor de hiv integrasa AR085857A1 (es)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US201161471658P 2011-04-04 2011-04-04
US201161481894P 2011-05-03 2011-05-03

Publications (1)

Publication Number Publication Date
AR085857A1 true AR085857A1 (es) 2013-10-30

Family

ID=45937692

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP120101177A AR085857A1 (es) 2011-04-04 2012-04-04 Proceso para la preparacion de un inhibidor de hiv integrasa

Country Status (8)

Country Link
US (1) US20140094610A1 (es)
EP (1) EP2694479A1 (es)
JP (1) JP2014511859A (es)
AR (1) AR085857A1 (es)
AU (1) AU2012240314A1 (es)
CA (1) CA2830838A1 (es)
TW (1) TW201302760A (es)
WO (1) WO2012138670A1 (es)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
NZ585226A (en) 2007-11-16 2012-08-31 Gilead Sciences Inc Inhibitors of human immunodeficiency virus replication
WO2012003498A1 (en) 2010-07-02 2012-01-05 Gilead Sciences, Inc. 2 -quinolinyl- acetic acid derivatives as hiv antiviral compounds
PT2588450T (pt) 2010-07-02 2017-08-03 Gilead Sciences Inc Derivados do ácido naft-2-ilacético para tratamento da sida
AP2015008931A0 (en) 2011-04-21 2015-12-31 Gilead Sciences Inc Benzothiazole compounds and their pharmaceutical use
WO2013103738A1 (en) 2012-01-04 2013-07-11 Gilead Sciences, Inc. Napthalene acetic acid derivatives against hiv infection
WO2013103724A1 (en) 2012-01-04 2013-07-11 Gilead Sciences, Inc. 2- (tert - butoxy) -2- (7 -methylquinolin- 6 - yl) acetic acid derivatives for treating aids
TWI480271B (zh) 2012-04-20 2015-04-11 Gilead Sciences Inc 醫療性化合物
WO2014055603A1 (en) * 2012-10-03 2014-04-10 Gilead Sciences, Inc. Process for the preparation of an hiv integrase inhibitor
WO2015179448A1 (en) * 2014-05-21 2015-11-26 Gilead Sciences, Inc. Therapeutic compounds
AU2015370004B2 (en) 2014-12-26 2021-03-11 Emory University N4-hydroxycytidine and derivatives and anti-viral uses related thereto
SG11202004403QA (en) 2017-12-07 2020-06-29 Univ Emory N4-hydroxycytidine and derivatives and anti-viral uses related thereto
CN111228247B (zh) * 2019-12-05 2023-01-31 青海大学 一种用于治疗包虫病的含苯亚甲基丙酮药物及其制备方法

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US7939545B2 (en) 2006-05-16 2011-05-10 Boehringer Ingelheim International Gmbh Inhibitors of human immunodeficiency virus replication
JP5006059B2 (ja) * 2007-01-29 2012-08-22 エリック エム． カレイラ キラルなイリジウムアクア錯体およびそれを用いた光学活性ヒドロキシ化合物の製造方法
CA2705318C (en) * 2007-11-15 2013-12-31 Boehringer Ingelheim International Gmbh Inhibitors of human immunodeficiency virus replication
EP2220095B1 (en) * 2007-11-15 2013-01-02 Gilead Sciences, Inc. Inhibitors of human immunodeficiency virus replication
NZ585226A (en) * 2007-11-16 2012-08-31 Gilead Sciences Inc Inhibitors of human immunodeficiency virus replication
US8338441B2 (en) * 2009-05-15 2012-12-25 Gilead Sciences, Inc. Inhibitors of human immunodeficiency virus replication
JP2014510139A (ja) * 2011-04-04 2014-04-24 ギリアード サイエンシーズ， インコーポレイテッド 固体形態のｈｉｖ阻害剤

Also Published As

Publication number Publication date
EP2694479A1 (en) 2014-02-12
JP2014511859A (ja) 2014-05-19
TW201302760A (zh) 2013-01-16
AU2012240314A1 (en) 2013-05-02
US20140094610A1 (en) 2014-04-03
WO2012138670A1 (en) 2012-10-11
CA2830838A1 (en) 2012-11-10

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