CA2903314C - Methods of synthesizing a difluorolactam analog - Google Patents

Methods of synthesizing a difluorolactam analog Download PDF

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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
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Prior art keywords
formula
compound
methyl
mmol
date received
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CA2903314A
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English (en)
French (fr)
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CA2903314A1 (en
Inventor
Stephen Douglas Barrett
Joseph Michael Colombo
Bradlee David Germain
Andriy Kornilov
James Bernard Kramer
Adam Uzieblo
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Cayman Chemical Co Inc
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Cayman Chemical Co Inc
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    • 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

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Medicinal Chemistry (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Pharmacology & Pharmacy (AREA)
  • General Chemical & Material Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Public Health (AREA)
  • Veterinary Medicine (AREA)
  • Engineering & Computer Science (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Biochemistry (AREA)
  • Molecular Biology (AREA)
  • Rheumatology (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Ophthalmology & Optometry (AREA)
  • Neurology (AREA)
  • Biomedical Technology (AREA)
  • Pain & Pain Management (AREA)
  • Neurosurgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
  • Plural Heterocyclic Compounds (AREA)
  • Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
  • Pyrrole Compounds (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
  • Medicines That Contain Protein Lipid Enzymes And Other Medicines (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 (enExample)
EP (1) EP2970234B1 (enExample)
JP (1) JP6368351B2 (enExample)
AU (1) AU2014229065B2 (enExample)
CA (1) CA2903314C (enExample)
IL (1) IL241042B (enExample)
WO (1) WO2014144500A2 (enExample)

Families Citing this family (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
EP2875022B1 (en) * 2012-07-19 2016-10-12 Cayman Chemical Company, Incorporated Difluorolactam compounds as ep4 receptor-selective agonists for use in the treatment of ep4-mediated disease and conditions
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
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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
EA200300379A1 (ru) 2000-11-27 2003-08-28 Пфайзер Продактс Инк. Селективные агонисты рецептора ep4 в лечении остеопороза
AU2002226035A1 (en) * 2000-12-07 2002-06-18 Michael P Doyle Lewis acid catalysis using chiral metal complexes
JP2004521954A (ja) 2001-07-16 2004-07-22 エフ．ホフマン−ラ　ロシュ　アーゲー Ｅｐ４受容体作用薬としてのプロスタグランジン類似体
PL215425B1 (pl) 2001-07-16 2013-12-31 Ono Pharmaceutical Co Pochodna pirolidonu, srodek farmaceutyczny zawierajacy te pochodna i jej zastosowanie
JP4273407B2 (ja) * 2001-07-23 2009-06-03 小野薬品工業株式会社 Ｅｐ４アゴニストを有効成分とする骨量低下疾患の治療剤
AU2002346562A1 (en) 2001-12-03 2003-06-17 Merck & Co., Inc. Method for treating ocular hypertension
ATE336247T1 (de) 2002-03-18 2006-09-15 Pfizer Prod Inc Verwendung von selektiven ep4 rezeptor agonisten zur behandlung von krankheiten
EP1513589B1 (en) 2002-06-06 2010-11-10 Merck Frosst Canada Ltd. 1,5-disubstituted pyrrolid-2-one derivatives for use as ep4 receptor agonists in the treatment of eye diseases such as glaucoma
AU2003237520B2 (en) 2002-06-10 2009-01-08 Laboratoires Serono Sa Gamma lactams as prostaglandin agonists and use thereof
WO2004037786A2 (en) 2002-10-25 2004-05-06 Merck Frosst Canada & Co. 2-pyrrolidones as ep4 receptor agonists
JP4662926B2 (ja) 2003-03-03 2011-03-30 メルク セローノ ソシエテ アノニム プロスタグランジン作動薬としてのγ−ラクタム誘導体
CN101821279A (zh) * 2007-08-15 2010-09-01 赛特凯恩蒂克公司 某些化学个体、组合物和方法
EP2215084B1 (en) 2007-10-23 2016-09-28 Allergan, Inc. Therapeutic substituted lactams
WO2011003058A1 (en) 2009-07-03 2011-01-06 Concert Pharmaceuticals, Inc. Prostacyclin derivatives
EP2638008B1 (en) 2010-11-10 2015-07-01 Actelion Pharmaceuticals Ltd Lactam derivatives useful as orexin receptor antagonists
PL2729445T3 (pl) * 2011-07-04 2016-04-29 Rottapharm Biotech Srl Cykliczne pochodne aminowe jako antagoniści receptora EP4
EP2875022B1 (en) 2012-07-19 2016-10-12 Cayman Chemical Company, Incorporated Difluorolactam compounds as ep4 receptor-selective agonists for use in the treatment of ep4-mediated disease and conditions

Also Published As

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

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