AR046938A1 - Procedimiento para preparar hexahidropirimido[1,2-a]azepin-2-carboxilatos y compuetos similares - Google Patents

Procedimiento para preparar hexahidropirimido[1,2-a]azepin-2-carboxilatos y compuetos similares

Info

Publication number
AR046938A1
AR046938A1 ARP040104493A ARP040104493A AR046938A1 AR 046938 A1 AR046938 A1 AR 046938A1 AR P040104493 A ARP040104493 A AR P040104493A AR P040104493 A ARP040104493 A AR P040104493A AR 046938 A1 AR046938 A1 AR 046938A1
Authority
AR
Argentina
Prior art keywords
alkyl
compound
formula
independently
halo
Prior art date
Application number
ARP040104493A
Other languages
English (en)
Original Assignee
Merck & Co Inc
Banyu Pharma Co Ltd
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 Merck & Co Inc, Banyu Pharma Co Ltd filed Critical Merck & Co Inc
Publication of AR046938A1 publication Critical patent/AR046938A1/es

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
    • C07F9/00—Compounds containing elements of Groups 5 or 15 of the Periodic System
    • C07F9/02—Phosphorus compounds
    • C07F9/547—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom
    • C07F9/6561—Heterocyclic compounds, e.g. containing phosphorus as a ring hetero atom containing systems of two or more relevant hetero rings condensed among themselves or condensed with a common carbocyclic ring or ring system, with or without other non-condensed hetero rings
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/12—Antivirals
    • A61P31/14—Antivirals for RNA viruses
    • A61P31/18—Antivirals for RNA viruses for HIV
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C251/00—Compounds containing nitrogen atoms doubly-bound to a carbon skeleton
    • C07C251/32—Oximes
    • C07C251/50—Oximes having oxygen atoms of oxyimino groups bound to carbon atoms of substituted hydrocarbon radicals
    • C07C251/60—Oximes having oxygen atoms of oxyimino groups bound to carbon atoms of substituted hydrocarbon radicals of hydrocarbon radicals substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C255/00—Carboxylic acid nitriles
    • C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
    • C07C255/24—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton
    • C07C255/26—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound nitrogen atoms, not being further bound to other hetero atoms, bound to the same saturated acyclic carbon skeleton containing cyano groups, amino groups and singly-bound oxygen atoms bound to the carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
    • C07C259/12—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. N-hydroxyamidines
    • C07C259/14—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups with replacement of the other oxygen atom of the carboxyl group by nitrogen atoms, e.g. N-hydroxyamidines having carbon atoms of hydroxamidine groups bound to hydrogen atoms or to acyclic carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
    • C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
    • C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
    • C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
    • C07D239/52—Two oxygen atoms
    • C07D239/54—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals
    • C07D239/545—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
    • C07D239/557—Two oxygen atoms as doubly bound oxygen atoms or as unsubstituted hydroxy radicals with other hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms, e.g. orotic acid
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
    • C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
    • C07D487/04—Ortho-condensed systems

Abstract

Se describen procedimientos para preparar 10-amino-3-hidroxi-4-oxo-4,6,7,8,9,10-hexahidropirimido[1,2-a]azepin-2-carboxilatos y compuestos relacionados. Se describe también la preparacion de derivados de carboxamida a partir de estos carboxilatos. Las carboxamidas son inhibidoras de integrasa del VIH y son utiles para tratar la infeccion con VIH y el SIDA. Reivindicacion 1: Un procedimiento para preparar un compuesto de formulas (1) o (2), el cual comprende: poner en contacto un compuesto de formula (3), o un compuesto de formula (4), con una base fuerte para obtener compuesto de formula (1); o poner en contacto un compuesto de formula (5), un compuesto de formula (6), un compuesto de formula (7), o un compuesto de formula (8), con una base fuerte para obtener el compuesto de formula (2); en el que W es un grupo protector amina; L es un grupo activador hidroxi; Y es halo; R1 es: a) H; b) alquilo (C1-6); c) alquilo (C1-6) sustituido con O-alquilo(C1-6), cicloalquilo (C3-8), o arilo, en el que el cicloalquilo está opcionalmente sustituido con de 1 a 3 grupos alquilo (C1-6) y el arilo está opcionalmente sustituido con de 1 a 5 sustituyentes cada uno de los cuales es independientemente alquilo (C1-6), O-alquilo (C1-6), CF3, OCF3, halo, CN o NO2; o d) arilo el cual está opcionalmente sustituido con de 1 a 5 sustituyentes cada uno de los cuales es independientemente alquilo (C1-6), O-alquilo(C1-6), CF3, OCF3, halo, CN, o NO2; R2, R4, cada R4, cada R5, R6, y R7 son independientemente: a) H; b) alquilo (C1-6); o c) alquilo (C1-6) sustituido con O-alquilo(C1-6), cicloalquilo (C3-8), o arilo, en el que el cicloalquilo está opcionalmente sustituido con de 1 a 3 grupos alquilo (C1-6) y el arilo está opcionalmente sustituido con de 1 a 5 sustituyentes cada uno de los cuales es independientemente alquilo (C1-6), O-alquilo (C1-6), CF3, OCF3, halo, CN o NO2; R8 es i) una mezcla de RA y RB, en la que RA y Rb son diferentes grupos alquilo (C1-6), o es ii) RC, en el que RC es un alquilo (C1-6); cada arilo es independientemente fenilo o naftilo; y n es un numero entero igual a cero, 1, 2 o 3; T es un grupo de formulas (9), U1, U2 y U3 se seleccionan cada uno independientemente del grupo que consiste en H, halo, alquilo (C1-6), O-alquilo(C1-6), fluoroalquilo (C1-6), -SO2-alquilo(C1-6), C(=O)-NH-(alquilo (C1-6)), C(=O)-N-(alquilo (C1-6))2, y HetA; V1 es H, halo, alquilo (C1-6), o fluoroalquilo (C1-6); y cada HetA es independientemente un anillo heteroaromático de 5 o 6 miembros de 1 a 4 heteroátomos seleccionados independientemente de N, O y S, en el que el anillo heteroaromático se sustituye opcionalmente con 1 o 2 grupos alquilo (C1-6).
ARP040104493A 2003-12-12 2004-12-02 Procedimiento para preparar hexahidropirimido[1,2-a]azepin-2-carboxilatos y compuetos similares AR046938A1 (es)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US52870403P 2003-12-12 2003-12-12

Publications (1)

Publication Number Publication Date
AR046938A1 true AR046938A1 (es) 2006-01-04

Family

ID=34710093

Family Applications (1)

Application Number Title Priority Date Filing Date
ARP040104493A AR046938A1 (es) 2003-12-12 2004-12-02 Procedimiento para preparar hexahidropirimido[1,2-a]azepin-2-carboxilatos y compuetos similares

Country Status (8)

Country Link
US (1) US20070142635A1 (es)
EP (1) EP1694678A2 (es)
JP (1) JP2007513958A (es)
AR (1) AR046938A1 (es)
AU (1) AU2004303856A1 (es)
CA (1) CA2547159A1 (es)
TW (1) TW200530198A (es)
WO (1) WO2005061501A2 (es)

Families Citing this family (36)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU2003292437A1 (en) * 2002-12-27 2004-07-22 Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa Tetrahydro-4h-pyrido(1,2-a)pyrimidines and related compounds useful as hiv integrase inhibitors
WO2004062613A2 (en) 2003-01-13 2004-07-29 Bristol-Myers Squibb Company Hiv integrase inhibitors
US7273859B2 (en) 2004-05-12 2007-09-25 Bristol-Myers Squibb Company HIV integrase inhibitors: cyclic pyrimidinone compounds
US7115601B2 (en) 2004-05-18 2006-10-03 Bristol-Myers Squibb Company HIV integrase inhibitors
US7173022B2 (en) 2004-05-28 2007-02-06 Bristol-Myers Squibb Company Bicyclic heterocycles as HIV integrase inhibitors
US7176196B2 (en) 2004-05-28 2007-02-13 Bristol-Myers Squibb Company Bicyclic heterocycles as HIV integrase inhibitors
US7157447B2 (en) 2004-05-28 2007-01-02 Bristol-Myers Squibb Company Bicyclic heterocycles as HIV integrase inhibitors
US7192948B2 (en) 2004-05-28 2007-03-20 Bristol-Myers Squibb Company Bicyclic heterocycles as HIV integrase inhibitors
WO2006060225A2 (en) * 2004-11-23 2006-06-08 Merck & Co., Inc. Process for asymmetric synthesis of hexahydropyrimido[1,2-a] azepine-2-carboxamides and related compounds
US7494984B2 (en) 2005-08-31 2009-02-24 Bristol-Myers Squibb Company Substituted imidazo[1,2-a]pyrimidines as HIV viral DNA integrase inhibitors
WO2007059125A2 (en) 2005-11-15 2007-05-24 Bristol-Myers Squibb Company Hiv integrase inhibitors
US7902182B2 (en) 2005-11-16 2011-03-08 Bristol-Myers Squibb Company HIV integrase inhibitors
US8039458B2 (en) 2005-11-17 2011-10-18 Bristol-Myers Squibb Company HIV integrase inhibitors
WO2007143446A1 (en) 2006-05-30 2007-12-13 Bristol-Myers Squibb Company Spiro-condensed heterotricyclic compounds as hiv integrase inhibitors
US7893055B2 (en) 2006-06-28 2011-02-22 Bristol-Myers Squibb Company HIV integrase inhibitors
US7763630B2 (en) 2007-06-06 2010-07-27 Bristol-Myers Squibb Company HIV integrase inhibitors
US8129398B2 (en) 2008-03-19 2012-03-06 Bristol-Myers Squibb Company HIV integrase inhibitors
CN102239172A (zh) * 2008-10-06 2011-11-09 默沙东公司 Hiv整合酶抑制剂
US8143244B2 (en) 2009-02-26 2012-03-27 Bristol-Myers Squibb Company Cyclopropyl fused indolobenzazepine HCV NS5B inhibitors
US8383639B2 (en) 2009-10-15 2013-02-26 Bristol-Myers Squibb Company HIV integrase inhibitors
US8835411B2 (en) 2010-12-10 2014-09-16 Bristol-Myers Squibb Company HIV integrase inhibitors
US8846659B2 (en) 2010-12-10 2014-09-30 Bristol-Myers Squibb Company HIV integrase inhibitors
WO2014008636A1 (en) * 2012-07-11 2014-01-16 Merck Sharp & Dohme Corp. Macrocyclic compounds as hiv integrase inhibitors
WO2014099586A1 (en) 2012-12-17 2014-06-26 Merck Sharp & Dohme Corp. 4-pyridinonetriazine derivatives as hiv integrase inhibitors
US9493479B2 (en) 2013-04-16 2016-11-15 Merck Sharp & Dohme Corp. Substituted pyrido[1,2-a]pyrazines as HIV integrase inhibitors
SI2997033T1 (en) 2013-05-17 2018-04-30 Merck Sharp & Dohme Corp. FUZYCLE TRICYCLE HETEROCYCLIC COMPOUNDS AS HIV INTEGRATED INHIBITORS
US9951079B2 (en) 2013-06-13 2018-04-24 Merck Sharp & Dohme Corp. Fused tricyclic heterocyclic compounds as HIV integrase inhibitors
JP6081662B2 (ja) 2013-09-27 2017-02-15 メルク・シャープ・アンド・ドーム・コーポレーションＭｅｒｃｋ Ｓｈａｒｐ ＆ Ｄｏｈｍｅ Ｃｏｒｐ． Ｈｉｖインテグラーゼ阻害薬として有用な置換されたキノリジン誘導体
CN107108540B (zh) * 2014-11-04 2019-08-02 日产化学工业株式会社 丁内酯化合物和制造方法
WO2016187788A1 (en) 2015-05-25 2016-12-01 Merck Sharp & Dohme Corp. Fused tricyclic heterocyclic compounds useful for treating hiv infection
EP3377066B1 (en) 2015-11-17 2021-04-07 Merck Sharp & Dohme Corp. Amido-substituted pyridotriazine derivatives useful as hiv integrase inhibitors
US10544155B2 (en) 2015-12-15 2020-01-28 Merck Sharp & Dohme Corp. Spirocyclic quinolizine derivatives useful as HIV integrase inhibitors
WO2017113288A1 (en) 2015-12-31 2017-07-06 Merck Sharp & Dohme Corp. Fused tricyclic heterocyclic compounds as hiv integrase inhibitors
CN110062627A (zh) 2016-12-02 2019-07-26 默沙东公司 可用作hiv整合酶抑制剂的三环杂环化合物
JOP20190130A1 (ar) 2016-12-02 2019-06-02 Merck Sharp & Dohme مركبات حلقية غير متجانسة رباعية الحلقات مفيدة كمثبطات إنزيم مدمج لفيروس نقص المناعة البشرية (hiv)
US10786488B2 (en) 2017-01-26 2020-09-29 Merck Sharp & Dohme Corp. Substituted quinolizine derivatives useful as HIV integrase inhibitors

Family Cites Families (7)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
HU185925B (en) * 1977-12-29 1985-04-28 Chinoin Gyogyszer Es Vegyeszet Process for preparing compounds with nitrogen bridge head
HU184058B (en) * 1977-12-29 1984-06-28 Chinoin Gyogyszer Es Vegyeszet Process for preparing new compounds with nitrogen bridge head
GB0017676D0 (en) * 2000-07-19 2000-09-06 Angeletti P Ist Richerche Bio Inhibitors of viral polymerase
DK1441735T3 (da) * 2001-10-26 2006-06-12 Angeletti P Ist Richerche Bio N-substituerede hydroxypyrimidinon-carboxamid-inhibitorer af HIV-integrase
DE60218511T2 (de) * 2001-10-26 2007-10-25 Istituto Di Richerche Di Biologia Molecolare P. Angeletti S.P.A. Dihydroxypyrimidin-carbonsäueramid-hemmer der hiv-integrase
GB0201179D0 (en) * 2002-01-18 2002-03-06 Angeletti P Ist Richerche Bio Therapeutic agents
AU2003292437A1 (en) * 2002-12-27 2004-07-22 Istituto Di Ricerche Di Biologia Molecolare P. Angeletti Spa Tetrahydro-4h-pyrido(1,2-a)pyrimidines and related compounds useful as hiv integrase inhibitors

Also Published As

Publication number Publication date
JP2007513958A (ja) 2007-05-31
CA2547159A1 (en) 2005-07-07
AU2004303856A1 (en) 2005-07-07
TW200530198A (en) 2005-09-16
WO2005061501A2 (en) 2005-07-07
WO2005061501A3 (en) 2006-04-06
US20070142635A1 (en) 2007-06-21
EP1694678A2 (en) 2006-08-30

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