WO2006123762A1 - Procede de production de composes de pyrrolidine - Google Patents

Procede de production de composes de pyrrolidine Download PDF

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Publication number
WO2006123762A1
WO2006123762A1 PCT/JP2006/309980 JP2006309980W WO2006123762A1 WO 2006123762 A1 WO2006123762 A1 WO 2006123762A1 JP 2006309980 W JP2006309980 W JP 2006309980W WO 2006123762 A1 WO2006123762 A1 WO 2006123762A1
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WIPO (PCT)
Prior art keywords
group
difluorophenyl
butyl
pyrrolidine
trans
Prior art date
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PCT/JP2006/309980
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English (en)
Japanese (ja)
Inventor
Tetsuya Ikemoto
Syoji Fukuyo
Junichi Yasuoka
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Sumitomo Chemical Company, Limited
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Publication date
Application filed by Sumitomo Chemical Company, Limited filed Critical Sumitomo Chemical Company, Limited
Publication of WO2006123762A1 publication Critical patent/WO2006123762A1/fr

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Classifications

    • 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
    • C07D207/04—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 no double bonds between ring members or between ring members and non-ring members
    • C07D207/10—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 no 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
    • C07D207/16—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
    • 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

Definitions

  • the present invention relates to a method for producing a pyrrolidine compound useful as a pharmaceutical, agricultural chemical, organic electronic material or the like, or an intermediate thereof, more specifically, production of an N-trisubstituted methyl- ⁇ -lance-3,4-disubstituted pyrrolidine compound. Regarding the method.
  • the — group, —S— group and —NH— group are not adjacent to each other X is an electron-withdrawing group R and X do not represent absolute configurations, but each other with respect to the pyrrolidine ring Indicates that it is located in the trans position.
  • tr an s— 1— t—Petitrou 4 (2, 4-difluorophenyl) monopyrrolidine—3—streptyl ethyl ester is useful as a melanocortin —4 (MC— 4) receptor agonist.
  • MC— 4 melanocortin —4
  • compound (3) has a sterically very crowded tri-substituted methyl group, and as a synthesis method thereof, for example, WO04 / 092126 discloses the method described in the following scheme 1. .
  • An object of the present invention is to provide a method capable of efficiently producing a compound (3) having a sterically hindered tri-substituted methyl group without using expensive reagents or ultra-low temperature conditions.
  • the gist of the present invention is as follows.
  • a compound represented by the formula (hereinafter sometimes referred to as compound (1)) is represented by formula (2)
  • a method comprising reacting a compound represented by the formula (hereinafter sometimes referred to as compound (2)) or a salt thereof in the presence of formaldehyde or a derivative thereof.
  • ⁇ 4> The method according to any one of ⁇ 1> to ⁇ 3>, wherein R is an optionally substituted phenyl group or an optionally substituted alkyl group.
  • X is a group represented by the formula (V), a group represented by the formula (VI), a formyl group, a cyano group or a two-necked group.
  • Rx is an optionally substituted aromatic group, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted alkenyl group or an optionally substituted Represents an alkynyl group.
  • Compound (1) is 3- (2,4-difluorophenyl) ethyl acrylate, 3- (2,4-difluorophenyl) methyl acrylate, 3- (2,4-difluorophenyl) acrylic acid t-butyl, 3- (2,4-difluorophenyl) benzyl acrylate, 3- (2,4-difluorophenyl) acrylate L-menthyl or optically active 3- 3- (2, 4-difluorophenyl) acrylic acid 3 _ (4,4-Dimethyl _2 1-year-old oxo)
  • the method according to any one of ⁇ 1> to ⁇ 4>, which is tetrahydrofuranyl.
  • Compound (2) is N—t-butylglycine, N— (1-methyl-1-phenyl) ethylglycine, N_ (1-cyclohexyl-1-ethyl) ethylglycine, From 1—, ⁇ 5> to N— (1-aryl-1-methyl) ethylglycine, N— (1,1-diphenyl) ethylglycine, N_triphenylmethyldaricin or N-tricyclohexylglycine 9> The method according to any one of the above.
  • the compound (3) is trans-1- 1-tert-butyl-4-41 (2,4-difluoro-orcenyl) pyrrolidine-3-streptyl ethyl sulfonate, trans-1- 1-tert-butyl-4 1 (2 , 4-Difluorophenyl) Pyrrolidine mono 3 _methyl carboxylate, trans mono l _ t-Butyl 4-1 (2,4-Difluorophenyl) Pyrrolidine mono 3-Strength isopropyl sulfonate, trans- 1- t-Butyl 4-one (2 , 4-difluorophenyl) pyrrolidine mono-3-t-butyl sulfonate, trans- 1- t-butyl -4- (2,4-difluorophenyl) pyrrolidine- 3-carboxylate, optically active tr an s— 1 _ t-Butyl— 4— (2, 4-Difluoro-or
  • ⁇ 1 3> The method according to any one of ⁇ 1> to ⁇ 1 2>, wherein the formaldehyde or a derivative thereof is paraformaldehyde, trioxane, a formalin aqueous solution, methoxymethane, or dimethoxymethane.
  • alkyl group in “optionally substituted alkyl group” include methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec_butyl group, t-butyl group, pentyl group.
  • a straight chain or branched chain having 1 to 12 carbon atoms such as a group, isopentyl group, neopentyl group, hexyl group, 2-ethylbutyl group, heptyl group, octyl group, nonyl group, decyl group, undecyl group, dodecyl group, etc.
  • An alkyl group is mentioned.
  • cycloalkyl group in the “optionally substituted cycloalkyl group” include a cyclopropyl group, a cyclobutyl group, a cyclopentyl group, a cyclohexyl group, a cycloheptyl group, etc. Cycloalkyl groups.
  • alkenyl group in “optionally substituted alkenyl group” include ethenyl group, 1-propenyl group, allyl group, 1-methyl-2-propenyl group, 1-butenyl group, 2- Butenyl group, 3-butenyl group, 1-pentenyl group, 2-pentenyl group, 1-hexenyl group, 2-hexenyl group, 1-heptenyl group, 2-heptenyl group, 1-octenyl group, 2-octenyl group, Examples thereof include linear or branched alkenyl groups having 2 to 12 carbon atoms such as 1-nonenyl group, 2-nonenyl group, 1-decenyl group, 2-decenyl group, 1-undecenyl group, 1-dodecenyl group.
  • alkynyl group in “optionally substituted alkynyl group” include ethynyl, 1-propynyl, 2_propynyl, 1-methyl-2-propynyl, 1-butynyl, 2-butynyl, 3-butynyl, 1 —Pentynyl, 2-pentynyl, 1-hexynyl, 2-hexynyl, 1-heptynyl, 2-heptynyl, 1-octynyl, 2-octynyl, 1-nonynyl, 2-nonynyl, 1-decynyl, Examples thereof include straight-chain or branched alkynyl groups having 2 to 12 carbon atoms such as 2-decynyl, 1-undecynyl, and 1-dodecyl.
  • the —O— group, _S— group, and —NH— group are not adjacent to each other.
  • Examples thereof include methoxymethyl group, methoxy group, t-butoxymethyl group, methoxyethoxymethyl group, methylthiomethyl group, 2-dimethylaminoethyl group, dimethylamino group, 2-jetylaminoethoxymethyl group, 4-methyl group.
  • Toxicyclohexyl group, 4-dimethylaminocyclohexyl group, tetrahydro-2-/-pyran-2-yloxymethyl group, 3-acetylpropyl group, 2-acetyloxychetyl group, bivalyloxymethyl group, 4-a Riloxybutyl group and the like are included.
  • alkyl group examples include a phenyl group, a naphthyl group, a furanyl group, a chenyl group, a pyridyl group, Benzofuranyl group, indoyl group, benzophenyl group, pyrimidyl group, birazinyl group, quinolinyl group, isoquinolinyl group, phthalazinyl group, quinazolinyl group, quinoxalinyl group, cinnolinyl group, halogen atom, nitro group, cyano group, etc. .
  • the number of substituents is not particularly limited, but 1 to 3 is preferable. When two or more substituents are present, they may be the same or different.
  • aromatic group in the “optionally substituted aromatic group” examples include an aromatic hydrocarbon group having 6 to 14 carbon atoms (for example, phenyl group, naphthyl group, etc.); nitrogen other than carbon atom 5- to 7-membered aromatic heterocyclic groups having 1 to 3 heteroatoms selected from atoms, oxygen atoms and sulfur atoms (for example, furanyl group, chenyl group, pyridyl group, pyrimidyl group, birazinyl group)
  • a condensed ring group composed of the same or different aromatic heterocycles for example, naphthyridinyl group, imidazopyrimidinyl group, pyridopyrazinyl group, pyrimidovirazinyl group, pyro-oral pyrimidinyl group, etc.
  • a condensed ring group consisting of a telo ring and the above aromatic hydrocarbon eg, benzofuranyl group, indolyl group, benzoche
  • Examples of the substituent that the “aromatic group” may have include: a halogen atom; a nitro group; a cyan group; an “optionally substituted alkyl group” as defined above; and a “substituted” as defined above.
  • R is preferably an optionally substituted phenyl group or an optionally substituted alkyl group, more preferably a phenyl group substituted with a fluorine atom or a methyl group, and particularly preferably a 2,4-difluorophenyl group.
  • Examples of the electron withdrawing group include a group represented by the following formula (V), a group represented by the formula (VI), a formyl group, a nitrile group, and a nitro group.
  • R x represents an optionally substituted aromatic group, an optionally substituted alkyl group, an optionally substituted cycloalkyl group, an optionally substituted alkenyl group, or an optionally substituted group; Good alkynyl group.
  • R x is preferably an alkyl group which may be substituted, and more preferably a methyl group or an ethyl group.
  • X is preferably a group represented by the formula (V), more preferably a methoxycarbonyl group or an ethoxycarbonyl group.
  • an optically active substituent having an asymmetric center in Rx an asymmetry is induced at positions 3 and 4 of the pyrrolidine ring of the obtained compound (3) to obtain an optically active compound (3). Can do. Then, by removing the Rx group by hydrolysis or oxidation treatment, it can be led to a photoactive pyrrolidine compound. Therefore, the use of an optically active substituent having an asymmetric center in Rx is advantageous for obtaining an optically active pyrrolidine compound.
  • the “alkenyl group” and the “optionally substituted alkynyl group” have the same meanings as defined for R, and each of the “alkyl group”, “cycloalkyl group”, “alkenyl group” ”And“ Alkynyl group ”, one or more of —CH 2 _ groups may be substituted with one group, one S— group, —NH— group or —CO— group.
  • Examples of compound (1) are: 3_ (2,4-difluorophenyl) ethyl acrylate, 3_ (2,4-difluorophenyl) methyl acrylate, 3- (2,4-difluorophenyl) acrylic Isopropyl acid, 3- (2,4-difluorophenyl) t-butyl acrylate, 3- (2,4-difluorophenyl) benzyl acrylate, optically active 1- (2,4-difluorophenyl) menthyl acrylate, Optically active 3- (2,4-difluorophenyl) acrylic acid 3— (4,4-dimethyl_2-oxo) tetrahydrofuranyl, 3— (2,4-difluorophenyl) acrylonitrile, 3— (2, 5-Difluorophenyl) Ethyl acrylate, 3 _ (2-Fluorophenyl) Methyl acrylate
  • Examples of compounds (2) include N—t _ butylglycine, N— (1 methyl-1-phenyl) ethylglycine, N— (1-cyclohexyl-1-methyl) ethylglycine, N- (1-aryl) 1-methyl) ethylglycine, N- (1,1-diphenyl) ethylglycine, N-triphenylmethylglycine, N-tricyclohexylmethyldaricin, N- (1-methoxy-1-methyl) ethylglycine, N- ( 1— (1— (N, N-dimethylamino) — 1—methyl) ethyl glycine, N_ (1—methylthio— 1—methyl) ethyl glycine, N— (1-acetyl- 1-methyl) ethyl glycine, N— (1-acetylyloxy— 1 -Methyl) ethylglycine, etc.,
  • trans-1 _ t-butyl-4_ (2, 4-difluorophenyl) pyrrolidine 1-3 carboxylate ethyl
  • trans _1-t butyl-4- (2, 4-difluoro Phenyl) Pyrrolidine—3—Strength methyl sulfonate
  • trans _ 1— t-Petilu 4_ (2,4-Difluorophenyl) Pyrrolidine—3—Isopropyl carbonate
  • optically active trans _ 1- t-butyl- 4_ (2, 4-difluorophenyl) pyrrolidine _ 3 _ Menthyl carboxylate
  • R and X do not indicate absolute configuration, but indicate that they are arranged in trans position with respect to the pyrrolidine ring.
  • trans is 1-tert-butyl-4 where R is a 2,4-difluorophenyl group, X is an ethoxycarbonyl group, and R 1 , R 2 and R 3 are all methyl groups.
  • R is a 2,4-difluorophenyl group
  • X is an ethoxycarbonyl group
  • R 1 , R 2 and R 3 are all methyl groups.
  • Formaldehyde or its derivatives are formaldehyde, formaldehyde polymer, formaldehyde cyclic, formaldehyde hydrate, formaldehyde and alcohol hemiacetal, formaldehyde and alcohol diacetal, formaldehyde and alkylene diol cyclic alcohol Refers to 1 liter etc. Specific examples include formaldehyde, paraformaldehyde, trioxane, formalin aqueous solution, methoxymethanol, ethoxymethanol, propoxymethanol, isopropoxymethanol, butoxymethanol, isobutoxymethanol, t-butoxymethanol, dimethylmethane, diethoxymethane, and dimethoxymethane.
  • Compound (2) has an amine and a carboxylic acid, and may form an acid addition salt or a salt with a base.
  • Compound (3) has a pyrrolidine ring and may form an acid addition salt.
  • an acid or base may be added as appropriate during the reaction to neutralize it.
  • acid addition salts include inorganic acid salts (eg, hydrochloride, sulfate, nitrate, phosphate, etc.); organic acid salts (eg, acetate, propionate, methanesulfonate, 4_toluenesulfonate,
  • salts with bases include alkali metal salts (for example, sodium salts and potassium salts); alkaline earth metal salts (for example, calcium salts and magnesium salts); organic And basic salts (for example, trimethylamine salt, triethylamine salt, pyridine salt, picoline salt, dicyclohexylamine salt, etc.).
  • Compound (1) is an aldol reaction between a compound represented by CH 3 X (where X is as defined above) and a compound represented by R—CH 0 (where R is as defined above) 2 XCOO H (where X is as defined above) and RCH 0 (where R is as defined above) Nevena-gel reaction, or B rCH 2 X (where X is A compound represented by the following formula: a Wittig reagent or Horner-Emmons reagent prepared from triphenylphosphine or dialkoxyphosphine and a compound represented by RCH 2 O (R is as defined above) It is prepared by a general reaction such as the Wützig reaction or the Horner-Emmons reaction. On the other hand, the compound (2) It is prepared by a condensation reaction between a haloacetic acid and a compound represented by RiRSRSNH (RR 2 and R 3 are as defined above). Detailed production method of compound (3)
  • Compound (3) can be obtained by reacting compound (1) with compound (2) in the presence of formaldehyde or a derivative thereof.
  • formaldehyde or a derivative thereof for example, the methods described in [1] to [6] below can be given, and a method in which they are partially combined can also be mentioned.
  • the compound (2) and formaldehyde or a derivative solution thereof may be sufficiently reacted in advance before adding the compound (1). Further, as a modification of [2] and [6], the compound (2) and formaldehyde or its derivative are mixed and then sufficiently reacted in advance, and the reaction solution is dispersed or dissolved in the compound (1). Examples of the method include adding them to the inside, and a method of combining them partially.
  • the amount of compound (2) is usually 1 to 10 mol, preferably 1 to 4 mol, more preferably 2 to 4 mol, per 1 mol of compound (1).
  • Formaldehyde or its invitation The amount of the conductor is usually 1 to 20 moles, preferably 1 to 10 moles, and more preferably 2 to 6 moles relative to 1 mole of the compound (1).
  • the solvent is not particularly limited as long as it does not inhibit the reaction.
  • an aliphatic hydrocarbon solvent, an aromatic solvent, an ether solvent, an alcohol solvent, a chlorinated hydrocarbon, and the like can be suitably used.
  • ether solvents are more preferred.
  • aliphatic hydrocarbon solvents examples include n-pentane, n-hexane, isohexane, n-heptane, isoheptane, n-octane, isooctane, n-nonane, isononane, n-decane, isodecane, n- Examples include undecane, n-dodecane, cyclopentane, cyclohexane, methylcyclohexane, t-butylcyclohexane, and petroleum ether.
  • aromatic solvents examples include benzene, toluene, ethylbenzene, isopropyl benzene, t-butylbenzene, xylene, mesitylene, monochlorobenzene, monofluorobenzene, H, H, ⁇ -trifluoromethylbenzene, 1, 2—
  • ether solvents include tetrahydrofuran, methyltetrahydrofuran, jetyl ether, di-eta-propyl ether, diisopropyl pill ether, di-eta-butyl ether, di-eta-pentyl ether, di-eta-hexyl ether, di-eta-heptyl ether. 1 ter, di ⁇ -octyl ether, t-butyl methyl ether, cyclopentyl methyl ether, 1,2_dimethyl shetan, diethylene glycol dimethyl ether, anisole, diphenyl ether and the like.
  • alcohol solvents include methanol, ethanol, isopropyl alcohol, n-butyl alcohol, isobutyl alcohol, t-butyl alcohol, n-pentanol, 2-pentanol, isopentyl alcohol, n-hexanol, 2 _Hexanol, isohexyl alcohol, n-heptanol, 2-heptanol, 3-heptanol, isoheptyl alcohol, ethylene glycol monomethyl ether, ethylene glycol monoethyl ether, ethylene glycol mono n-propyl ether, ethylene glycol monoisopropyl ether, ethylene dallicol mono n_butyl ether, ethylene glycol monoisobutyl ether, ethylene glycol mono t-butyl ether, diethylene glycol monomethyl Ether, diethylene glycol Examples thereof include rumonoethyl ether, diethylene glycol mono n-propyl ether,
  • the amount of the solvent is usually 1 to: L 00 L, preferably 5 to 50 L with respect to 1 kg of compound (1) from the viewpoints of stirrability and reaction time.
  • the reaction time is usually 1 to 48 hours, and the reaction temperature is usually 50 to 200 ° C., preferably 100 to L: 50 ° C.
  • An appropriate catalyst may be added to the reaction solution to promote the reaction.
  • the catalyst those having the effect of lowering the LUMO (lowest orbital orbital) of the compound (1) are preferable, and for example, Lewis acid, amino acid, secondary amine and the like are preferable.
  • this catalyst is an optically active substance, or compound (3) can be obtained as an optically active substance by adding an optically active ligand.
  • Isolation of compound (3) can be carried out by subjecting the reaction solution to post-treatment by a conventional method (for example, neutralization, extraction, washing with water, salt formation, crystallization, etc.).
  • a conventional method for example, neutralization, extraction, washing with water, salt formation, crystallization, etc.

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  • Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Abstract

La présente invention concerne un procédé de production de composés représentés par la formule générale (3) ou des sels de ceux-ci : (3) qui comprend la mise en réaction d’un composé représenté par la formule générale (1) : (1) avec un composé représenté par la formule générale (2) ou un sel de celui-ci : (2) en présence de formaldéhyde ou d’un dérivé de celui-ci.
PCT/JP2006/309980 2005-05-16 2006-05-12 Procede de production de composes de pyrrolidine WO2006123762A1 (fr)

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JP2005143251 2005-05-16

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Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012027573A2 (fr) * 2010-08-25 2012-03-01 University Of Massachusetts Polymère biodégradable à mémoire de forme

Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003528072A (ja) * 2000-03-17 2003-09-24 ブリストル−マイヤーズ スクイブ ファーマ カンパニー マトリックスメタロプロテアーゼおよびＴＮＦ−αの阻害剤としての環状β−アミノ酸誘導体
WO2004092126A2 (fr) * 2003-04-14 2004-10-28 Merck & Co., Inc. Procede et intermediaires pour la preparation d'acides carboxyliques de pyrrolidine

Patent Citations (2)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2003528072A (ja) * 2000-03-17 2003-09-24 ブリストル−マイヤーズ スクイブ ファーマ カンパニー マトリックスメタロプロテアーゼおよびＴＮＦ−αの阻害剤としての環状β−アミノ酸誘導体
WO2004092126A2 (fr) * 2003-04-14 2004-10-28 Merck & Co., Inc. Procede et intermediaires pour la preparation d'acides carboxyliques de pyrrolidine

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
JOUCLA M.: "2,5-Unsubstituted pyrrolidines from formaldehyde and amino acids through in situ azomethine-ylide 1,3-bipolar cycloaddition to alkenes", J. CHEM. SOC. CHEM. COMMUN., no. 22, 1985, pages 1566 - 1567, XP000568856 *
TRAVNICEK M.: "Pyrrolidine and 1,3-oxazolidine formation from azomethine ylides influenced by change from classical conditions to microwave irradiation", ARKIVOC (GAINESVILLE, FL, UNITED STATES), no. 5, 2001, pages 156 - 163, XP003006493, Retrieved from the Internet <URL:http://www.arkat-usa.org/ark/journal/Volume2/Part3/Tisler/MT-316B/316B.pdf> *
VIRANYI A.: "A Convenient Synthesis of Pyrrolo [3,4-c] quinolines", SYNTHESIS, no. 17, 2003, pages 2655 - 2660, XP002996137 *

Cited By (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2012027573A2 (fr) * 2010-08-25 2012-03-01 University Of Massachusetts Polymère biodégradable à mémoire de forme
WO2012027573A3 (fr) * 2010-08-25 2012-07-05 University Of Massachusetts Polymère biodégradable à mémoire de forme
US9163114B2 (en) 2010-08-25 2015-10-20 University Of Massachusetts Biodegradable shape memory polymer

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