CA2903314C - Methods of synthesizing a difluorolactam analog - Google Patents

Methods of synthesizing a difluorolactam analog Download PDF

Info

Publication number
CA2903314C
CA2903314C CA2903314A CA2903314A CA2903314C CA 2903314 C CA2903314 C CA 2903314C CA 2903314 A CA2903314 A CA 2903314A CA 2903314 A CA2903314 A CA 2903314A CA 2903314 C CA2903314 C CA 2903314C
Authority
CA
Canada
Prior art keywords
formula
compound
methyl
mmol
date received
Prior art date
Legal status (The legal status 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 status listed.)
Active
Application number
CA2903314A
Other languages
English (en)
French (fr)
Other versions
CA2903314A1 (en
Inventor
Stephen Douglas Barrett
Joseph Michael Colombo
Bradlee David Germain
Andriy Kornilov
James Bernard Kramer
Adam Uzieblo
Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)
Cayman Chemical Co Inc
Original Assignee
Cayman Chemical Co 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 Cayman Chemical Co Inc filed Critical Cayman Chemical Co Inc
Publication of CA2903314A1 publication Critical patent/CA2903314A1/en
Application granted granted Critical
Publication of CA2903314C publication Critical patent/CA2903314C/en
Active legal-status Critical Current
Anticipated expiration legal-status Critical

Links

Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D409/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms
    • C07D409/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings
    • C07D409/06—Heterocyclic compounds containing two or more hetero rings, at least one ring having sulfur atoms as the only ring hetero atoms containing two hetero rings linked by a carbon chain containing only aliphatic carbon atoms
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P19/00—Drugs for skeletal disorders
    • A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
    • A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/04—Centrally acting analgesics, e.g. opioids
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P27/00—Drugs for disorders of the senses
    • A61P27/02—Ophthalmic agents
    • A61P27/06—Antiglaucoma agents or miotics
    • 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
    • C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
    • C07B39/00—Halogenation
    • 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
    • C07D207/273—2-Pyrrolidones 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 other ring carbon atoms
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
    • C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
    • C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
    • C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur 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
    • C07D333/38—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D498/00—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms
    • C07D498/02—Heterocyclic compounds containing in the condensed system at least one hetero ring having nitrogen and oxygen atoms as the only ring hetero atoms in which the condensed system contains two hetero rings
    • C07D498/04—Ortho-condensed systems
    • 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 Table
    • C07F9/02—Phosphorus compounds
    • C07F9/28—Phosphorus compounds with one or more P—C bonds
    • C07F9/38—Phosphonic acids [RP(=O)(OH)2]; Thiophosphonic acids ; [RP(=X1)(X2H)2(X1, X2 are each independently O, S or Se)]
    • C07F9/40—Esters thereof
    • C07F9/4003—Esters thereof the acid moiety containing a substituent or a structure which is considered as characteristic
    • C07F9/4006—Esters of acyclic acids which can have further substituents on alkyl

Landscapes

  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • General Chemical & Material Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Molecular Biology (AREA)
  • Biochemistry (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Rheumatology (AREA)
  • Ophthalmology & Optometry (AREA)
  • Neurology (AREA)
  • Neurosurgery (AREA)
  • Pain & Pain Management (AREA)
  • Biomedical Technology (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Pyrrole Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
CA2903314A 2013-03-15 2014-03-14 Methods of synthesizing a difluorolactam analog Active CA2903314C (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
US201361799334P 2013-03-15 2013-03-15
US61/799,334 2013-03-15
PCT/US2014/028933 WO2014144500A2 (en) 2013-03-15 2014-03-14 Methods of synthesizing a difluorolactam analog

Publications (2)

Publication Number Publication Date
CA2903314A1 CA2903314A1 (en) 2014-09-18
CA2903314C true CA2903314C (en) 2023-02-14

Family

ID=50693998

Family Applications (1)

Application Number Title Priority Date Filing Date
CA2903314A Active CA2903314C (en) 2013-03-15 2014-03-14 Methods of synthesizing a difluorolactam analog

Country Status (7)

Country Link
US (3) US9914725B2 (https=)
EP (1) EP2970234B1 (https=)
JP (1) JP6368351B2 (https=)
AU (1) AU2014229065B2 (https=)
CA (1) CA2903314C (https=)
IL (1) IL241042B (https=)
WO (1) WO2014144500A2 (https=)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
CN107802623B (zh) * 2012-07-19 2020-10-30 开曼化学股份有限公司 用于ep4介导的骨相关疾病和病症的二氟内酰胺组合物
HU231033B1 (hu) * 2016-03-22 2019-12-30 CHINOIN Gyógyszer és Vegyészeti Termékek Gyára Zrt. Eljárás 3-as kötést tartalmazó optikailag aktív karbonsavak, karbonsav sók és karbonsav származékok előállítására
CN106699604B (zh) * 2017-01-09 2019-01-01 四川同晟生物医药有限公司 一种沙库比曲及其中间体的制备方法

Family Cites Families (26)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US3975399A (en) 1974-08-06 1976-08-17 E. I. Du Pont De Nemours And Company 1,5-Disubstituted-2-pyrrolidinones, -3-pyrrolin-2-ones, and -4-pyrrolin-2-ones
DE2517771A1 (de) 1975-04-18 1976-10-28 Schering Ag Neue prostaglandin-acetylen-analoga und verfahren zu ihrer herstellung
CA1085859A (en) 1975-06-27 1980-09-16 Wilhelm Bartmann Pyrrolidones and process for their manufacture
DE2528664A1 (de) 1975-06-27 1977-01-13 Hoechst Ag Pyrrolidone und verfahren zu ihrer herstellung
DE2619638A1 (de) 1976-05-04 1977-11-17 Hoechst Ag Pyrrolidone und verfahren zu ihrer herstellung
US4177346A (en) 1976-08-06 1979-12-04 Pfizer Inc. 1,5-Disubstituted-2-pyrrolidones
US4320136A (en) 1980-08-11 1982-03-16 E. I. Du Pont De Nemours And Company 8-Aza-16,16-difluoroprostanoids
US4311644A (en) * 1981-01-30 1982-01-19 E. R. Squibb & Sons, Inc. Method for preparing 10,10-difluoro prostacyclin intermediates and new compounds produced thereby
US4456613A (en) 1982-12-27 1984-06-26 E. I. Du Pont De Nemours And Company 6-Keto- and 6-hydroxy-8-azaprostanoids and anti-ulcer use thereof
PT1339678E (pt) 2000-11-27 2007-11-30 Pfizer Prod Inc Agonistas selectivos do receptor ep4 no tratamento de osteoporose
AU2002226035A1 (en) * 2000-12-07 2002-06-18 Michael P Doyle Lewis acid catalysis using chiral metal complexes
RU2296122C2 (ru) 2001-07-16 2007-03-27 Ф.Хоффманн-Ля Рош Аг Производные 2-пирролидона в качестве простаноидных агонистов и фармацевтическая композиция
ES2254726T3 (es) 2001-07-16 2006-06-16 F. Hoffmann-La Roche Ag Analogos de prostaglandina como agonistas receptores de ep4.
NZ530885A (en) * 2001-07-23 2007-09-28 Ono Pharmaceutical Co Remedies for diseases with bone mass loss having EP4 agonist as the active ingredient
CA2466757A1 (en) 2001-12-03 2003-06-12 Merck & Co., Inc. Method for treating ocular hypertension
CA2478653A1 (en) 2002-03-18 2003-09-25 Pfizer Products Inc. Methods of treatment with selective ep4 receptor agonists
DE60334905D1 (de) 2002-06-06 2010-12-23 Merck Frosst Canada Ltd 1,5-disubstituierte pyrrolid-2-on-derivate zur verwendung als ep4 rezeptor agonisten zur behandlung von augenkrankheiten wie z.b. glaukom
US7419999B2 (en) 2002-06-10 2008-09-02 Applied Research Systems Ars Holding N.V. Gamma lactams as prostaglandin agonists and use thereof
AU2003275840A1 (en) 2002-10-25 2004-05-13 Merck Frosst Canada Ltd 2-pyrrolidones as EP4 receptor agonists
ATE394372T1 (de) 2003-03-03 2008-05-15 Serono Lab G-lactamderivate als prostaglandinagonisten
US8088793B2 (en) 2007-08-15 2012-01-03 Cytokinetics, Inc. Certain chemical entities, compositions, and methods
KR20100086485A (ko) 2007-10-23 2010-07-30 알러간, 인코포레이티드 치료적 치환된 락탐
US20120270934A1 (en) 2009-07-03 2012-10-25 Concert Pharmaceuticals, Inc. Prostacyclin derivatives
CA2815179A1 (en) 2010-11-10 2012-05-18 Actelion Pharmaceuticals Ltd Lactam derivatives useful as orexin receptor antagonists
DK2729445T3 (en) * 2011-07-04 2016-01-18 Rottapharm Biotech Srl CYCLIC AMINE DERIVATIVES AS EP4 RECEPTOR ANTAGONISTS
CN107802623B (zh) * 2012-07-19 2020-10-30 开曼化学股份有限公司 用于ep4介导的骨相关疾病和病症的二氟内酰胺组合物

Also Published As

Publication number Publication date
WO2014144500A2 (en) 2014-09-18
US9914725B2 (en) 2018-03-13
EP2970234B1 (en) 2018-07-18
US20190202816A1 (en) 2019-07-04
US20160060253A1 (en) 2016-03-03
AU2014229065A1 (en) 2015-09-17
US20220127252A9 (en) 2022-04-28
AU2014229065B2 (en) 2017-03-09
IL241042B (en) 2021-10-31
CA2903314A1 (en) 2014-09-18
JP6368351B2 (ja) 2018-08-01
HK1215022A1 (en) 2016-08-12
JP2016519669A (ja) 2016-07-07
EP2970234A2 (en) 2016-01-20
WO2014144500A3 (en) 2015-05-28
US11345690B2 (en) 2022-05-31
IL241042A0 (en) 2015-11-30
US20180170918A1 (en) 2018-06-21

Similar Documents

Publication Publication Date Title
KR102473601B1 (ko) Ep4 길항약과 면역 체크 포인트 저해약을 포함하여 이루어진 조합
JP6234471B2 (ja) スピロ環状イソキサゾリン誘導体の合成
ES2610428T3 (es) Compuestos de difluorolactama como agonistas selectivos del receptor EP4 para su uso en el tratamiento de enfermedades y afecciones mediadas por EP4
CA2903314C (en) Methods of synthesizing a difluorolactam analog
ES2875551T3 (es) Método para preparar (R)-4-n-propil-dihidrofuran-2(3H)-ona ópticamente pura
JP2023550612A (ja) 大環状ｍｃｌ１阻害剤を調製するための方法及び中間体
AU2014228973B2 (en) Lactam compounds as EP4 receptor-selective agonists for use in the treatment of EP4-mediated diseases and conditions
JP5646706B2 (ja) Ｃ−グリコシド誘導体の製造方法
Li et al. PhI (OAc) 2-mediated additions of 2, 4-dinitrophenylsulfenamide with methylenecyclopropanes (MCPs) and a methylenecyclobutane (MCB)
JP7113542B2 (ja) 複素環式化合物及びその医学的応用
EP4662326A1 (en) Ligand-enabled transannular c-h functionalization of cycloalkane carboxylic acids
TW202440095A (zh) 三環性化合物
JP5829529B2 (ja) 光学活性４級アンモニウム塩、および光学活性化合物の製造方法
Zhou et al. Flexible syntheses of 5, 8-disubstituted indolizidine poisonous-frog alkaloids via a Michael-type conjugate addition
Sánta et al. Synthesis of pure methyl [(2S, 3R, αR)-1-(3-bromo-4-methoxyphenyl)-3-(α-acetoxy) ethyl-4-oxoazetidin-2-carboxylate] and its enantiomer
WO2025144882A1 (en) Enantioselective remote methylene c-h (hetero)arylation of cycloalkane carboxylic acids
AU2013295723A1 (en) Therapeutic compounds
Csuk et al. From a glycal to a [1, 3] dioxolan-4-yl ester
HK1205937B (en) Difluorolactam compositions for ep4-mediated osteo related diseases and conditions

Legal Events

Date Code Title Description
EEER Examination request

Effective date: 20190307

W00 Other event occurred

Free format text: ST27 STATUS EVENT CODE: A-4-4-W10-W00-W100 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: LETTER SENT

Effective date: 20251203

H13 Ip right lapsed

Free format text: ST27 STATUS EVENT CODE: N-4-6-H10-H13-H100 (AS PROVIDED BY THE NATIONAL OFFICE); EVENT TEXT: MAINTENANCE FEE AND LATE FEE NOT PAID BY DEADLINE OF NOTICE

Effective date: 20260317