HUP0203365A2 - Synthetic routes for the preparation of rhinovirus protease inhibitors and their intermediates - Google Patents

Synthetic routes for the preparation of rhinovirus protease inhibitors and their intermediates

Info

Publication number
HUP0203365A2
HUP0203365A2 HU0203365A HUP0203365A HUP0203365A2 HU P0203365 A2 HUP0203365 A2 HU P0203365A2 HU 0203365 A HU0203365 A HU 0203365A HU P0203365 A HUP0203365 A HU P0203365A HU P0203365 A2 HUP0203365 A2 HU P0203365A2
Authority
HU
Hungary
Prior art keywords
cycloalkyl
alkyl
heterocycloalkyl
group
independently
Prior art date
Application number
HU0203365A
Other languages
Hungarian (hu)
Inventor
Srinivasan Babu
Steven Lee Bender
Raymond Dagnino
Michael Joseph Melnick
Lennert J. Mitchell
Terence Jarold Moran
Naresh K. Nayyar
Travis Paul Remarchuk
Junhua Tao
Qingping Tian
Original Assignee
Agouron Pharmaceuticals 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 Agouron Pharmaceuticals Inc. filed Critical Agouron Pharmaceuticals Inc.
Publication of HUP0203365A2 publication Critical patent/HUP0203365A2/en
Publication of HUP0203365A3 publication Critical patent/HUP0203365A3/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)
  • Pyridine Compounds (AREA)
  • Hydrogenated Pyridines (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Peptides Or Proteins (AREA)
  • Enzymes And Modification Thereof (AREA)
  • Pyrrole Compounds (AREA)

Abstract

A találmány tárgyát hatékony szintézis eljárások képezik az (I)általános képletű rinovírus proteáz inhibitorok előállítására,valamint az eljárás új köztitermékei. Az (I) általános képletben R1jelentése H, F, alkilcsoport, -OH, -SH vagy -O-alkil-csoport; R2 és R3jelentése egymástól függetlenül H, (a) képletű vagy (b) általánosképletű csoport, R4 jelentése (c) általános képletű csoport, R5 és R6jelentése egymástól függetlenül H, F, alkilcsoport, cikloalkilcsoport,heterocikloalkilcsoport, arilcsoport vagy heteroarilcsoport; R7 és R8jelentése egymástól függetlenül H, alkilcsoport, cikloalkilcsoport,heterocikloalkilcsoport, arilcsoport, heteroarilcsoport, -OR17, -SR17,-NR17R18, -NR19NR17R18 vagy -NR17OR18 általános képletű csoport; R9 5-tagú heterogyűrűs csoport, amely 1 - 3 heteroatomot tartalmaz; ezekjelentése O, N és/vagy S; és Z és Z1 jelentése egymástól függetlenülH, F, alkil-, cikloalkil-, heterocikloalkil-, aril- vagyheteroarilcsoport, vagy -C(O)R21 -CO2R21, -CN, -C(O)NR21R22, -C(O)NR21OR22, -C(S)R21, -C(S)NR21R22, -NO2, -SOR21 -SO2R21, -SO2NR21R22, -SO(NR21)(OR22), -SONR21, -SO3R21, -PO(OR21)2, -PO(R21)(R22), -PO(NR21,R22)(OR23), -PO(NR21R22)(NR23R24), -C(O)NR21NR22R23 vagy -C(S)NR21NR22R23 általános képletű csoport, vagyR21, R22, R23 és R24 közül bármely kettő a közrezárt atommal vagyatomokkal, amelyhez kötődnek, heterocikloalkilcsoportot alkotnak; vagyZ1és R1 az atomokkal, amelyekhez kötődnek, cikloalkil- vagyheterocikloalkilcsoportot alkotnak; vagy Z és Z1 azokkal az atomokkal,amelyekhez kötődnek, cikloalkil- vagy heterocikloalkilcsoportotalkotnak. ÓThe subject of the invention are efficient synthesis methods for the production of rhinovirus protease inhibitors of the general formula (I), as well as new intermediate products of the process. In the general formula (I), R1 is H, F, alkyl, -OH, -SH or -O-alkyl; R2 and R3 are independently H, a group of formula (a) or (b), R4 is a group of formula (c), R5 and R6 are independently H, F, alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl; R7 and R8 are independently H, alkyl, cycloalkyl, heterocycloalkyl, aryl, heteroaryl, -OR17, -SR17, -NR17R18, -NR19NR17R18 or -NR17OR18; R9 is a 5-membered heterocyclic group containing 1 to 3 heteroatoms; their meaning is O, N and/or S; and Z and Z1 are independently H, F, alkyl, cycloalkyl, heterocycloalkyl, aryl or heteroaryl, or -C(O)R21 -CO2R21, -CN, -C(O)NR21R22, -C(O)NR21OR22, -C(S)R21, -C(S)NR21R22, -NO2, -SOR21 -SO2R21, -SO2NR21R22, -SO(NR21)(OR22), -SONR21, -SO3R21, -PO(OR21)2, -PO( R21)(R22), -PO(NR21,R22)(OR23), -PO(NR21R22)(NR23R24), -C(O)NR21NR22R23 or -C(S)NR21NR22R23, or R21, R22, R23 and R24 any two of which, together with the atom or atoms to which they are attached, form a heterocycloalkyl group; or Z 1 and R 1 together with the atoms to which they are attached form a cycloalkyl or heterocycloalkyl group; or Z and Z1 form a cycloalkyl or heterocycloalkyl group with the atoms to which they are attached. HE

HU0203365A 1999-08-24 2000-08-23 Synthetic routes for the preparation of rhinovirus protease inhibitors and their intermediates HUP0203365A3 (en)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US15035899P 1999-08-24 1999-08-24
PCT/US2000/023033 WO2001014329A1 (en) 1999-08-24 2000-08-23 Synthetic routes for the preparation of rhinovirus protease inhibitors and key intermediates

Publications (2)

Publication Number Publication Date
HUP0203365A2 true HUP0203365A2 (en) 2003-02-28
HUP0203365A3 HUP0203365A3 (en) 2003-12-29

Family

ID=22534156

Family Applications (1)

Application Number Title Priority Date Filing Date
HU0203365A HUP0203365A3 (en) 1999-08-24 2000-08-23 Synthetic routes for the preparation of rhinovirus protease inhibitors and their 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
DE69928140D1 (en) 1998-04-30 2005-12-08 Agouron Pharma Antipicornaviral compounds, their preparation and use
BR0012970A (en) 1999-08-04 2002-04-30 Agouron Pharma Antipicornaviral compounds and compositions, their pharmaceutical uses and materials for their synthesis
PE20020157A1 (en) 1999-12-03 2002-02-22 Agouron Pharma PYRIDONE DERIVED COMPOUNDS AS PICORNAVIRAL 3C PROTEASE INHIBITORS, COMPOSITIONS, THEIR PHARMACEUTICAL USES AND MATERIALS FOR THEIR SYNTHESIS
PE20011277A1 (en) 2000-04-14 2002-01-07 Agouron Pharma ANTIPICORNAVIRAL COMPOUNDS AND COMPOSITIONS, THEIR PHARMACEUTICAL USES AND THE MATERIALS FOR THEIR SYNTHESIS
EP1355878A2 (en) 2000-06-14 2003-10-29 Agouron Pharmaceuticals, Inc. Antipicornaviral compounds and compositions, their pharmaceutical uses, and materials for 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
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
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

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CA2254343A1 (en) * 1996-05-14 1997-11-20 Agouron Pharmaceuticals, Inc. Inhibitors of picornavirus 3c proteases and methods for their use and preparation
PT975588E (en) * 1997-03-28 2004-02-27 Agouron Pharma COMPOUNDS THAT CONTAIN THEM AND METHODS FOR THEIR USE
US5962487A (en) * 1997-12-16 1999-10-05 Agouron Pharmaceuticals, Inc. Antipicornaviral compounds and methods for their use and preparation
DE69928140D1 (en) * 1998-04-30 2005-12-08 Agouron Pharma Antipicornaviral compounds, their preparation and use

Also Published As

Publication number Publication date
IL147674A0 (en) 2002-08-14
CZ2002632A3 (en) 2003-04-16
BR0013306A (en) 2002-05-28
CN1374947A (en) 2002-10-16
AR025380A1 (en) 2002-11-20
MXPA02001944A (en) 2002-10-31
KR20020046283A (en) 2002-06-20
UY26307A1 (en) 2001-04-30
TWI245040B (en) 2005-12-11
AU6797100A (en) 2001-03-19
HK1049336B (en) 2005-05-20
PE20010517A1 (en) 2001-05-16
HK1049336A1 (en) 2003-05-09
EP1206450A1 (en) 2002-05-22
AU770221B2 (en) 2004-02-19
CA2376452A1 (en) 2001-03-01
PL353997A1 (en) 2003-12-15
HUP0203365A3 (en) 2003-12-29
WO2001014329A1 (en) 2001-03-01
JP2003507453A (en) 2003-02-25
ZA200200504B (en) 2003-03-26
CN1168713C (en) 2004-09-29
CO5200782A1 (en) 2002-09-27

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FD9A Lapse of provisional protection due to non-payment of fees