DK2639222T3 - Fremgangsmåder til fremstilling af cycloalkylcarboxamido-pyridinbenzoesyrer - Google Patents

Fremgangsmåder til fremstilling af cycloalkylcarboxamido-pyridinbenzoesyrer Download PDF

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Publication number
DK2639222T3
DK2639222T3 DK12196502.4T DK12196502T DK2639222T3 DK 2639222 T3 DK2639222 T3 DK 2639222T3 DK 12196502 T DK12196502 T DK 12196502T DK 2639222 T3 DK2639222 T3 DK 2639222T3
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compound
aspects
reaction
organic solvent
acid
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DK12196502.4T
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David Siesel
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Vertex Pharma
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/72—Nitrogen atoms
    • C07D213/73—Unsubstituted amino or imino radicals
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/433—Thidiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P11/00—Drugs for disorders of the respiratory system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P15/00—Drugs for genital or sexual disorders; Contraceptives
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
    • C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
    • C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
    • C07D213/60—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom 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
    • C07D213/72—Nitrogen atoms
    • C07D213/74—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
    • 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
    • C07D405/08—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 linked by a carbon chain containing alicyclic 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
    • C07D405/12—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 linked by a chain containing hetero atoms as chain links

Claims (15)

1. Fremgangsmåde til fremstilling afen forbindelse med formel 6a:
6a hvor, R er H, Ci-e alifatisk, aryl, aralkyl, heteroaryl, cycloalkyl, eller heterocycloalkyl; Ri er uafhængigt valgt fra -RJ, -ORJ, -N(RJ)2, -NO2, halogen, -CN, -Ci-4haloalkyl, -Ci-4haloalkoxy, -C(0)N(RJ)2, -NRJC(0)RJ, -SORJ, -S02RJ, -S02N(Rj)2,-NRjS02Rj, -CORj, -C02Rj, -NRjS02N(Rj)2, -COCORj; RJ er hydrogen eller C1-6 alifatisk; o er et helt tal fra 0 til 3 inklusiv; og p er et helt tal fra 0 til 5 inklusiv; omfattende trinnene at: ib) tilvejebringe forbindelse 2a og forbindelse 3a,
2a 3a ; hvor, Ri er uafhængigt valgt fra -RJ, -OR^, -N(RJ)2, -NO2, halogen, -CN, -Ci-4haloalkyl, -Ci-4haloalkoxy, -C(0)N(RJ)2, -NRJC(0)RJ, -SORJ, -S02RJ, -S02N(Rj)2,-NRjS02Rj, -CORj, -C02Rj, -NRjS02N(Rj)2, -COCORj; RJ er hydrogen eller C1-6 alifatisk; o er et helt tal fra 0 til 4 inklusiv; og p er et helt tal fra O til 5 inklusiv; iib) krydskoble forbindelse 2a og forbindelse 3a i en bifasisk blanding omfattende vand, et første organisk opløsningsmiddel, en første base, og en overgangsmetalkatalysator til at fremstille forbindelse 4a,
4a ; hvor, Ri, o, og p er som defineret for forbindelserne 2a og 3a ovenfor; iiib) oxidere forbindelse 4a til at fremstille forbindelse 5a,
5a ; hvor, Ri, o, og p er som defineret for forbindelserne 2a og 3a ovenfor; ivb) tilsætte en amingruppe til 6-stillingen af pyridylgruppen for at fremstille forbindelse 6a,
6a ; hvor amineringsreaktionen udføres i tilstedeværelse af en sulfonylforbindelse, hvor, R er H, Ci-6 alifatisk, aryl, aralkyl, heteroaryl, cycloalkyl, eller heterocycloalkyl; og Ri, o, og p er som defineret for forbindelserne 2a og 3a ovenfor.
2. Fremgangsmåden ifølge krav 1, hvor det første organiske opløsningsmiddel er et aprot opløsningsmiddel.
3. Fremgangsmåden ifølge krav 1, hvor det første organiske opløsningsmiddel er toluen.
4. Fremgangsmåden ifølge krav 1, hvor det første organiske opløsningsmiddel er et prot opløsningsmiddel.
5. Fremgangsmåden ifølge krav 1, hvor den første base er en uorganisk base.
6. Fremgangsmåden ifølge krav 1, hvor den første base er kaliumcarbonat.
7. Fremgangsmåden ifølge krav 1, hvor overgangsmetalkatalysatoren er en palladium-baseret katalysator.
8. Fremgangsmåden ifølge krav 1, hvor den palladium-baserede katalysator er Pd(dppf)CI2.
9. Fremgangsmåden ifølge krav 1, hvor krydskoblingsreaktionen foregår mellem 60°C og 100°C.
10. Fremgangsmåden ifølge krav 1, hvor oxidationsreaktionen udføres under anvendelse af peroxid.
11. Fremgangsmåden ifølge krav 1, hvor oxidationsreaktionen udføres under anvendelse af pereddikesyre.
12. Fremgangsmåden ifølge krav 1, hvor oxidationsreaktionen udføres i tilstedeværelse af et anhydrid.
13. Fremgangsmåden ifølge krav 1, hvor oxidationsreaktionen udføres i tilstedeværelse af phthalsyreanhydrid.
14. Fremgangsmåden ifølge krav 1, hvor oxidationsreaktionen foregår mellem 25°C og 65°C.
15. Fremgangsmåden ifølge krav 1, hvor amineringsreaktionen udføres i tilstedeværelse af methansulfonsyreanhydrid.
DK12196502.4T 2007-12-07 2008-12-04 Fremgangsmåder til fremstilling af cycloalkylcarboxamido-pyridinbenzoesyrer DK2639222T3 (da)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US1218107P 2007-12-07 2007-12-07
US10957308P 2008-10-30 2008-10-30
EP08859582A EP2231606B1 (en) 2007-12-07 2008-12-04 Processes for producing cycloalkylcarboxiamido-pyridine benzoic acids

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DK2639222T3 true DK2639222T3 (da) 2016-10-03

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DK08859582.2T DK2231606T3 (da) 2007-12-07 2008-12-04 Fremgangsmåder til fremstilling af cycloalkylcarboxamidopyridinbenzoesyrer
DK12196502.4T DK2639222T3 (da) 2007-12-07 2008-12-04 Fremgangsmåder til fremstilling af cycloalkylcarboxamido-pyridinbenzoesyrer
DK12196511.5T DK2639223T3 (da) 2007-12-07 2008-12-04 Fremgangsmåde til fremstilling af cycloalkylcarboxiamido-pyridinbenzosyrer
DK12196539.6T DK2639224T3 (da) 2007-12-07 2008-12-04 Fremgangsmåde til fremstilling af cycloalkylcarboxiamido-pyridinbenzoesyrer

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DK12196539.6T DK2639224T3 (da) 2007-12-07 2008-12-04 Fremgangsmåde til fremstilling af cycloalkylcarboxiamido-pyridinbenzoesyrer

Country Status (26)

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US (4) US8124781B2 (da)
EP (4) EP2639224B1 (da)
JP (4) JP5702149B2 (da)
KR (3) KR101612009B1 (da)
CN (2) CN101910134B (da)
AU (1) AU2008335440B2 (da)
BR (1) BRPI0820902A2 (da)
CA (3) CA2707494C (da)
CL (1) CL2010000631A1 (da)
CY (4) CY1113985T1 (da)
DK (4) DK2231606T3 (da)
EA (1) EA201070700A1 (da)
ES (4) ES2406940T3 (da)
HK (2) HK1146820A1 (da)
HR (4) HRP20130418T1 (da)
HU (3) HUE032268T2 (da)
IL (4) IL206205A (da)
LT (3) LT2639223T (da)
MX (4) MX364935B (da)
NZ (3) NZ599684A (da)
PL (4) PL2639222T3 (da)
PT (4) PT2639222T (da)
RS (4) RS55298B1 (da)
SI (4) SI2639224T1 (da)
WO (1) WO2009076142A2 (da)
ZA (1) ZA201003624B (da)

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