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PE20010517A1 - THE EFFICIENT SYNTHETIC ROUTES FOR THE PREPARATION OF RINOVIRUS PROTEASE INHIBITORS AND KEY INTERMEDIATES - Google Patents

THE EFFICIENT SYNTHETIC ROUTES FOR THE PREPARATION OF RINOVIRUS PROTEASE INHIBITORS AND KEY INTERMEDIATES

Info

Publication number
PE20010517A1
PE20010517A1 PE2000000854A PE0008542000A PE20010517A1 PE 20010517 A1 PE20010517 A1 PE 20010517A1 PE 2000000854 A PE2000000854 A PE 2000000854A PE 0008542000 A PE0008542000 A PE 0008542000A PE 20010517 A1 PE20010517 A1 PE 20010517A1
Authority
PE
Peru
Prior art keywords
compound
alkyl
rinovirus
preparation
produce
Prior art date
Application number
PE2000000854A
Other languages
Spanish (es)
Inventor
Quingping Tian
Naresh K Nayyar
Srinivasan Babu
Junhua Tao
Michael J Melnick
Steven L Bernder
Lennert J Mitchell
Terence J Moran
Raymond Dagnino Jr
Travis P Remarchuk
Original Assignee
Agouron Pharma
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 Agouron Pharma filed Critical Agouron Pharma
Publication of PE20010517A1 publication Critical patent/PE20010517A1/en

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Classifications

    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/24—Stationary reactors without moving elements inside
    • B01J19/2415—Tubular reactors
    • B01J19/2435—Loop-type reactors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
    • C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D207/18—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member
    • C07D207/22—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D207/24—Oxygen or sulfur atoms
    • C07D207/26—2-Pyrrolidones
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J19/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J19/24—Stationary reactors without moving elements inside
    • B01J19/2475—Membrane reactors
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
    • C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
    • C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
    • C07C271/06—Esters of carbamic acids
    • C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
    • C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/26—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids
    • C07C303/28—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids by reaction of hydroxy compounds with sulfonic acids or derivatives thereof
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
    • C07C69/66—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety
    • C07C69/73—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids
    • C07C69/732—Esters of carboxylic acids having esterified carboxylic groups bound to acyclic carbon atoms and having any of the groups OH, O—metal, —CHO, keto, ether, acyloxy, groups, groups, or in the acid moiety of unsaturated acids of unsaturated hydroxy carboxylic acids
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D261/00—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings
    • C07D261/02—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings
    • C07D261/06—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two or more double bonds between ring members or between ring members and non-ring members
    • C07D261/10—Heterocyclic compounds containing 1,2-oxazole or hydrogenated 1,2-oxazole rings not condensed with other rings having two 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, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
    • C07D261/18—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
    • C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00049—Controlling or regulating processes
    • B01J2219/00051—Controlling the temperature
    • B01J2219/00074—Controlling the temperature by indirect heating or cooling employing heat exchange fluids
    • B01J2219/00087—Controlling the temperature by indirect heating or cooling employing heat exchange fluids with heat exchange elements outside the reactor
    • B01J2219/00099—Controlling the temperature by indirect heating or cooling employing heat exchange fluids with heat exchange elements outside the reactor the reactor being immersed in the heat exchange medium
    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J2219/00—Chemical, physical or physico-chemical processes in general; Their relevant apparatus
    • B01J2219/00049—Controlling or regulating processes
    • B01J2219/00051—Controlling the temperature
    • B01J2219/00159—Controlling the temperature controlling multiple zones along the direction of flow, e.g. pre-heating and after-cooling

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Hydrogenated Pyridines (AREA)
  • Pyridine Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Pyrrole Compounds (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Abstract

SE REFIERE A UN PROCESO PARA LA SINTESIS DEL COMPUESTO I COMO ETILO-3-{(5`-METILISOXAZOL-3'-CARBONIL)-L-VALÝ(COCH2)-L-(4-F-Phe)-L-((S)-PIRROL-ALA)}-E-PROPANOATO, QUE COMPRENDE a)LA CIANOMETILACION DE UN COMPUESTO V UTILIZANDO BIS(TRIMETISILO)AMIDA Y BROMOACETONITRILO PARA PRODUCIR UN COMPUESTO VI; b)REALIZAR LA DISMINUCION , CICLIZACION, PROTECCION DEL COMPUESTO VI PARA PRODUCIR EL COMPUESTO VII; c)REALIZAR LA OXIDACION Y OLEFINACION DEL COMPEUSTO VII MEDIANTE LA REACCION DEL COMPUESTO VII CON UN COMPLEJO DE SO3-PIRIDINA PARA PRODUCIR UNA MEZCLA DE REACCION Y REACCIONAR CON UN COMPUESTO VIII Y FORMAR UN COMPUESTO IV; R1 ES H, F, ALQUILO, OH, SH, O-ALQUILO; R41 ES H, ALQUILO; X ES GRUPO PROTECTOR DE N; d)DESPROTEGER EL COMPUESTO IV PARA FORMAR UN COMPUESTO IVA; e)SOMETER (R4)(R5)(R6)C-C(=O)-OH Y EL COMPUESTO IVA PARA FORMAR EL COMPUESTO IA, R2 Y R3 SON H, -CH2-CO-NH2, GRUPO a; n ES 0-5; A1 ES CH, N; A2 Y A3 SON C(R41)2, S, ENTRE OTROS; R4 ES R9-CO-NH-C(R7)(R8)-CO-; R5 Y R6 SON H, F, ALQUILO, ENTRE OTROS: R7 Y R8 SON H, ALQUILO, ENTRE OTROS; R9 ES HETEROCICLO DE 5 MIEMBROS; Z Y Z1 SON H, F, ALQUILO, ENTRE OTROS. EL COMPUESTO V ES PREPARADO A PARTIR DE N-BOS L-ACIDO GLUTAMICO þ-BENZILO ESTER. TAMBIEN SE REFIERE A LA PREPARACION DE COMPUESTOS INTERMEDIOS. EL COMPUESTO ES UTIL PARA PREPARAR INHIBIDORES DE PROTEASA DEL RINOVIRUSREFERS TO A PROCESS FOR THE SYNTHESIS OF COMPOUND I AS ETHYL-3 - {(5`-METHYLISOXAZOLE-3'-CARBONYL) -L-VALÝ (COCH2) -L- (4-F-Phe) -L - (( S) -PYRROL-ALA)} - E-PROPANOATE, WHICH INCLUDES a) THE CYANOMETILATION OF A COMPOUND V USING BIS (TRIMETISILO) AMIDE AND BROMOACETONITRILE TO PRODUCE A COMPOUND VI; b) PERFORM THE DECREASE, CYCLING, PROTECTION OF COMPOUND VI TO PRODUCE COMPOUND VII; c) CARRY OUT THE OXIDATION AND OLEFINATION OF THE COMPEUST VII BY REACTIONING THE COMPOUND VII WITH A SO3-PYRIDINE COMPLEX TO PRODUCE A REACTION MIXTURE AND REACT WITH A COMPOUND VIII AND FORM A COMPOUND IV; R1 IS H, F, ALKYL, OH, SH, O-ALKYL; R41 IS H, ALKYL; X IS THE PROTECTIVE GROUP OF N; d) UNPROTECT COMPOUND IV TO FORM A COMPOUND VAT; e) SUBMIT (R4) (R5) (R6) C-C (= O) -OH AND THE COMPOUND IVA TO FORM THE COMPOUND IA, R2 AND R3 ARE H, -CH2-CO-NH2, GROUP a; n IS 0-5; A1 IS CH, N; A2 AND A3 ARE C (R41) 2, S, AMONG OTHERS; R4 IS R9-CO-NH-C (R7) (R8) -CO-; R5 AND R6 ARE H, F, ALKYL, AMONG OTHERS: R7 AND R8 ARE H, ALKYL, AMONG OTHERS; R9 IS A 5-MEMBER HETEROCYCLE; Z AND Z1 ARE H, F, RENT, AMONG OTHERS. COMPOUND V IS PREPARED FROM N-BOS L-GLUTAMIC ACID þ-BENZYL ESTER. IT ALSO REFERS TO THE PREPARATION OF INTERMEDIATE COMPOUNDS. THE COMPOUND IS USEFUL TO PREPARE RINOVIRUS PROTEASE INHIBITORS

PE2000000854A 1999-08-24 2000-08-22 THE EFFICIENT SYNTHETIC ROUTES FOR THE PREPARATION OF RINOVIRUS PROTEASE INHIBITORS AND KEY INTERMEDIATES PE20010517A1 (en)

Applications Claiming Priority (1)

Application Number Priority Date Filing Date Title
US15035899P 1999-08-24 1999-08-24

Publications (1)

Publication Number Publication Date
PE20010517A1 true PE20010517A1 (en) 2001-05-16

Family

ID=22534156

Family Applications (1)

Application Number Title Priority Date Filing Date
PE2000000854A PE20010517A1 (en) 1999-08-24 2000-08-22 THE EFFICIENT SYNTHETIC ROUTES FOR THE PREPARATION OF RINOVIRUS PROTEASE INHIBITORS AND KEY INTERMEDIATES

Country Status (20)

Country Link
EP (1) EP1206450A1 (en)
JP (1) JP2003507453A (en)
KR (1) KR20020046283A (en)
CN (1) CN1168713C (en)
AR (1) AR025380A1 (en)
AU (1) AU770221B2 (en)
BR (1) BR0013306A (en)
CA (1) CA2376452A1 (en)
CO (1) CO5200782A1 (en)
CZ (1) CZ2002632A3 (en)
HK (1) HK1049336B (en)
HU (1) HUP0203365A3 (en)
IL (1) IL147674A0 (en)
MX (1) MXPA02001944A (en)
PE (1) PE20010517A1 (en)
PL (1) PL353997A1 (en)
TW (1) TWI245040B (en)
UY (1) UY26307A1 (en)
WO (1) WO2001014329A1 (en)
ZA (1) ZA200200504B (en)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
SK284714B6 (en) 1998-04-30 2005-09-08 Agouron Pharmaceuticals, Inc. Antipicornaviral compounds, their use and pharmaceutical composition
AU779321B2 (en) 1999-08-04 2005-01-20 Agouron Pharmaceuticals, Inc. Antipicornaviral compounds and compositions, their pharmaceutical uses, and materials for their synthesis
PA8507801A1 (en) 1999-12-03 2002-08-26 Agouron Pharma ANTIPICORNAVIRAL COMPOUNDS AND COMPOSITIONS, THEIR PHARMACEUTICAL USES AND THE MATERIALS FOR SYNTHESIS
PA8515201A1 (en) 2000-04-14 2002-10-24 Agouron Pharma ANTIPICORNAVIRAL COMPOUNDS AND COMPOSITIONS; YOUR PHARMACEUTICAL USES AND MATERIALS FOR SYNTHESIS
CN1525957A (en) 2000-06-14 2004-09-01 ������ҩ�����޹�˾ Compounds and compositions against picornaviruses, their medicinal uses, and substances used in their synthesis
CN1309712C (en) * 2004-04-02 2007-04-11 中国科学院上海有机化学研究所 Precursor of key intermediate of AG 7088 class compound and its sythetic process
US20230157998A1 (en) 2020-03-06 2023-05-25 Pfizer Inc. Methods of Inhibiting SARS-CoV-2 Replication and Treating Corona Virus Disease 2019
CN115322130B (en) * 2022-08-02 2024-05-14 南京正济医药研究有限公司 Preparation of (S) -2- (BOC-amino) -3- [ (S) -2-oxo-3-pyrrolidinyl ] propanoic acid methyl ester
CN115260074B (en) * 2022-08-02 2024-06-21 爱斯特（成都）生物制药股份有限公司 Preparation method of oral antiviral drug Paxlovid intermediate

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
AU722704B2 (en) * 1996-05-14 2000-08-10 Agouron Pharmaceuticals, Inc. Inhibitors of picornavirus 3c proteases and methods for their use and preparation
ATE248809T1 (en) * 1997-03-28 2003-09-15 Agouron Pharma COMPOUNDS AGAINST PICORNA VIRUSES, COMPOSITIONS CONTAINING SUCH COMPOUNDS AND METHODS OF USE THEREOF
US5962487A (en) * 1997-12-16 1999-10-05 Agouron Pharmaceuticals, Inc. Antipicornaviral compounds and methods for their use and preparation
SK284714B6 (en) * 1998-04-30 2005-09-08 Agouron Pharmaceuticals, Inc. Antipicornaviral compounds, their use and pharmaceutical composition

Also Published As

Publication number Publication date
AU770221B2 (en) 2004-02-19
CA2376452A1 (en) 2001-03-01
CN1374947A (en) 2002-10-16
PL353997A1 (en) 2003-12-15
WO2001014329A1 (en) 2001-03-01
HK1049336A1 (en) 2003-05-09
IL147674A0 (en) 2002-08-14
HK1049336B (en) 2005-05-20
HUP0203365A2 (en) 2003-02-28
CO5200782A1 (en) 2002-09-27
KR20020046283A (en) 2002-06-20
BR0013306A (en) 2002-05-28
EP1206450A1 (en) 2002-05-22
CN1168713C (en) 2004-09-29
MXPA02001944A (en) 2002-10-31
ZA200200504B (en) 2003-03-26
UY26307A1 (en) 2001-04-30
CZ2002632A3 (en) 2003-04-16
AR025380A1 (en) 2002-11-20
AU6797100A (en) 2001-03-19
TWI245040B (en) 2005-12-11
JP2003507453A (en) 2003-02-25
HUP0203365A3 (en) 2003-12-29

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