DK2465541T3 - orbedrede fremgangsmåder til fremstilling af hydrazider - Google Patents

orbedrede fremgangsmåder til fremstilling af hydrazider Download PDF

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Publication number
DK2465541T3
DK2465541T3 DK12159159.8T DK12159159T DK2465541T3 DK 2465541 T3 DK2465541 T3 DK 2465541T3 DK 12159159 T DK12159159 T DK 12159159T DK 2465541 T3 DK2465541 T3 DK 2465541T3
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DK
Denmark
Prior art keywords
hydrazide
hydrazine
reaction
flask
product
Prior art date
Application number
DK12159159.8T
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English (en)
Inventor
George A Chiarello
Ayman Sahli
Original Assignee
Wyeth Llc
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.)
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Application filed by Wyeth Llc filed Critical Wyeth Llc
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Publication of DK2465541T3 publication Critical patent/DK2465541T3/da

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/14—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides
    • C07C319/20—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of sulfides by reactions not involving the formation of sulfide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C323/00—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups
    • C07C323/23—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton
    • C07C323/46—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having at least one of the nitrogen atoms, not being part of nitro or nitroso groups, further bound to other hetero atoms
    • C07C323/48—Thiols, sulfides, hydropolysulfides or polysulfides substituted by halogen, oxygen or nitrogen atoms, or by sulfur atoms not being part of thio groups containing thio groups and nitrogen atoms, not being part of nitro or nitroso groups, bound to the same carbon skeleton having at least one of the nitrogen atoms, not being part of nitro or nitroso groups, further bound to other hetero atoms to nitrogen atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K47/00—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient
    • A61K47/50—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates
    • A61K47/51—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent
    • A61K47/68—Medicinal preparations characterised by the non-active ingredients used, e.g. carriers or inert additives; Targeting or modifying agents chemically bound to the active ingredient the non-active ingredient being chemically bound to the active ingredient, e.g. polymer-drug conjugates the non-active ingredient being a modifying agent the modifying agent being an antibody, an immunoglobulin or a fragment thereof, e.g. an Fc-fragment
    • A61K47/6889—Conjugates wherein the antibody being the modifying agent and wherein the linker, binder or spacer confers particular properties to the conjugates, e.g. peptidic enzyme-labile linkers or acid-labile linkers, providing for an acid-labile immuno conjugate wherein the drug may be released from its antibody conjugated part in an acidic, e.g. tumoural or environment
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C241/00—Preparation of compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
    • C07C241/04—Preparation of hydrazides
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C243/00—Compounds containing chains of nitrogen atoms singly-bound to each other, e.g. hydrazines, triazanes
    • C07C243/24—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids
    • C07C243/26—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms
    • C07C243/28—Hydrazines having nitrogen atoms of hydrazine groups acylated by carboxylic acids with acylating carboxyl groups bound to hydrogen atoms or to acyclic carbon atoms to hydrogen atoms or to carbon atoms of a saturated carbon skeleton
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C319/00—Preparation of thiols, sulfides, hydropolysulfides or polysulfides
    • C07C319/02—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols
    • C07C319/12—Preparation of thiols, sulfides, hydropolysulfides or polysulfides of thiols by reactions not involving the formation of mercapto groups
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P20/00—Technologies relating to chemical industry
    • Y02P20/50—Improvements relating to the production of bulk chemicals
    • Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Epidemiology (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Health & Medical Sciences (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Immunology (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Peptides Or Proteins (AREA)
  • Medicines Containing Antibodies Or Antigens For Use As Internal Diagnostic Agents (AREA)
  • Coating Apparatus (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)

Claims (12)

1. Fremgangsmåde til fremstilling af en hydrazid med strukturen:
hvor P er en thiol-beskyttelsesgruppe, som er en benzylgruppe, eventuelt substitueret på phenyl ringen; Ri og R2 hver især er udvalgt fra gruppen bestående af C-i-Cs-alkyl; og L er en alkylenlinker, ud fra hydrazin og en acylchlorid med strukturen:
omfattende de følgende trin: (a) at fremstille en omrørt i det væsentlige ensartet opslæmning omfattende hydrazin og et inert opløsningsmiddel i et forhold på fra 5:95 til 19:81, i forhold til volumen, ved at afkøle det inerte opløsningsmiddel til en temperatur på fra -68 til -75 grader C, efterfulgt af en drypvis tilsætning af hydrazin til det kolde inerte opløsningsmiddel; og (b) at tilsætte acylchloridet kontinuerligt til opslæmningen, hvor den kontinuerlige tilsætning af acylchlorid indstilles til at opretholde en reaktionstemperatur på fra -68 °C til -75°C.
2. Fremgangsmåde ifølge krav 1, hvor acylchloridet tilsættes i det væsentlige drypvist til opslæmningen.
3. Fremgangsmåde ifølge krav 1 eller 2, hvor L er -CH2-.
4. Fremgangsmåde ifølge krav 1,2 eller 3, hvor Ri og R2 hver især uafhængigt er methyl.
5. Fremgangsmåde ifølge et af kravene 1 til 4, hvor P er p-methoxybenzyl-gruppe.
6. Fremgangsmåde ifølge krav 1 eller 2, hvor acylchloridet har strukturen:
7. Fremgangsmåde ifølge krav 1 eller 2, hvor det ønskede hydrazid er
8. Fremgangsmåde ifølge krav 1, hvor hydrazidet indeholder mindre end 5 % af et bis-hydrazid-biprodukt med strukturen:
hvor R og R' er
og hvor P, Ri, R2 og L er som defineret i krav 1.
9. Fremgangsmåde ifølge krav 8, hvor bis-hydrazid-biproduktet har en struktur:
10. Fremgangsmåde ifølge et af kravene 1 til 9, hvor den i det væsentlige ensartede opslæmning omfatter hydrazin, og et inert opløsningsmiddel fremstilles i et forhold på ca. 14:86, i forhold til volumen.
11. Fremgangsmåde til fremstilling af 3-methyl-3-mercaptobutansyrehydrazid omfattende et trin, hvor der fremstilles et hydrazid i henhold til fremgangsmåden ifølge krav 5.
12. Fremgangsmåde ifølge krav 11, hvor 3-methyl-3-mercaptobutansyrehy-drazid anvendes som en linker til at fremstille gemtuzumab-ozogamicin (MYLOTARG - Trade Mark) eller inotuzumab-ozogamicin.
DK12159159.8T 2007-05-22 2008-05-20 orbedrede fremgangsmåder til fremstilling af hydrazider DK2465541T3 (da)

Applications Claiming Priority (2)

Application Number Priority Date Filing Date Title
US93952907P 2007-05-22 2007-05-22
EP08755945.6A EP2155258B1 (en) 2007-05-22 2008-05-20 Improved processes for making hydrazides

Publications (1)

Publication Number Publication Date
DK2465541T3 true DK2465541T3 (da) 2018-09-17

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DK12159159.8T DK2465541T3 (da) 2007-05-22 2008-05-20 orbedrede fremgangsmåder til fremstilling af hydrazider

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Country Status (24)

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US (5) US8110705B2 (da)
EP (2) EP2155258B1 (da)
JP (4) JP5697446B2 (da)
KR (1) KR101547705B1 (da)
CN (2) CN101835494B (da)
AR (1) AR066674A1 (da)
AU (1) AU2008256905B2 (da)
BR (1) BRPI0811140B1 (da)
CA (1) CA2687852A1 (da)
CL (1) CL2008001490A1 (da)
CY (2) CY1119373T1 (da)
DK (2) DK2155258T3 (da)
ES (2) ES2686019T3 (da)
HU (2) HUE036704T2 (da)
IL (1) IL202242A (da)
MX (1) MX2009012587A (da)
PA (1) PA8781201A1 (da)
PE (1) PE20090305A1 (da)
PL (2) PL2155258T3 (da)
PT (2) PT2465541T (da)
SI (2) SI2465541T1 (da)
TW (1) TW200904784A (da)
WO (1) WO2008147765A1 (da)
ZA (1) ZA200908229B (da)

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Publication number Publication date
BRPI0811140B1 (pt) 2022-08-16
US20130211053A1 (en) 2013-08-15
WO2008147765A1 (en) 2008-12-04
JP5697446B2 (ja) 2015-04-08
CN102558001B (zh) 2015-09-23
US8110705B2 (en) 2012-02-07
AR066674A1 (es) 2009-09-02
EP2465541B1 (en) 2018-07-18
AU2008256905B2 (en) 2014-05-08
ES2642888T3 (es) 2017-11-20
RU2009143524A (ru) 2011-06-27
JP2017193584A (ja) 2017-10-26
IL202242A (en) 2016-03-31
US9227924B2 (en) 2016-01-05
JP2010528031A (ja) 2010-08-19
PL2465541T3 (pl) 2018-12-31
EP2155258B1 (en) 2017-08-16
PL2155258T3 (pl) 2017-12-29
HUE036704T2 (hu) 2018-07-30
EP2465541A1 (en) 2012-06-20
CY1120592T1 (el) 2019-12-11
BRPI0811140A2 (pt) 2015-10-27
EP2155258A1 (en) 2010-02-24
PT2465541T (pt) 2018-10-17
JP2013234203A (ja) 2013-11-21
TW200904784A (en) 2009-02-01
PA8781201A1 (es) 2008-12-18
US9738602B2 (en) 2017-08-22
CL2008001490A1 (es) 2008-07-25
KR20100031514A (ko) 2010-03-22
US20150099865A1 (en) 2015-04-09
JP2016026219A (ja) 2016-02-12
CA2687852A1 (en) 2008-12-04
US8853451B2 (en) 2014-10-07
CN101835494A (zh) 2010-09-15
SI2465541T1 (sl) 2018-10-30
US8383857B2 (en) 2013-02-26
US20120130052A1 (en) 2012-05-24
CY1119373T1 (el) 2018-02-14
CN101835494B (zh) 2012-02-15
PT2155258T (pt) 2017-10-18
ZA200908229B (en) 2010-08-25
KR101547705B1 (ko) 2015-08-26
IL202242A0 (en) 2010-06-16
HK1172008A1 (zh) 2013-04-12
HK1147736A1 (en) 2011-08-19
PE20090305A1 (es) 2009-03-15
MX2009012587A (es) 2010-05-14
SI2155258T1 (sl) 2017-10-30
AU2008256905A1 (en) 2008-12-04
ES2686019T3 (es) 2018-10-16
US20080312422A1 (en) 2008-12-18
DK2155258T3 (da) 2017-09-18
HUE039657T2 (hu) 2019-01-28
CN102558001A (zh) 2012-07-11
US20160176809A1 (en) 2016-06-23

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