WO2023048237A1 - Agent d'amino-fluoration et procédé de production d'un agent d'amino-fluoration - Google Patents

Agent d'amino-fluoration et procédé de production d'un agent d'amino-fluoration Download PDF

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WO2023048237A1
WO2023048237A1 PCT/JP2022/035395 JP2022035395W WO2023048237A1 WO 2023048237 A1 WO2023048237 A1 WO 2023048237A1 JP 2022035395 W JP2022035395 W JP 2022035395W WO 2023048237 A1 WO2023048237 A1 WO 2023048237A1
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compound
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amino
nmr
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隆 岡添
光介 相川
京子 野崎
悠貴 伊藤
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Ａｇｃ株式会社
国立大学法人東京大学
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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C209/00—Preparation of compounds containing amino groups bound to a carbon skeleton
    • C07C209/62—Preparation of compounds containing amino groups bound to a carbon skeleton by cleaving carbon-to-nitrogen, sulfur-to-nitrogen, or phosphorus-to-nitrogen bonds, e.g. hydrolysis of amides, N-dealkylation of amines or quaternary ammonium compounds
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C211/00—Compounds containing amino groups bound to a carbon skeleton
    • C07C211/01—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms
    • C07C211/26—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring
    • C07C211/29—Compounds containing amino groups bound to a carbon skeleton having amino groups bound to acyclic carbon atoms of an unsaturated carbon skeleton containing at least one six-membered aromatic ring the carbon skeleton being further substituted by halogen atoms or by nitro or nitroso groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
    • C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
    • C07C303/40—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids by reactions not involving the formation of sulfonamide groups
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/15—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings
    • C07C311/16—Sulfonamides having sulfur atoms of sulfonamide groups bound to carbon atoms of six-membered aromatic rings having the nitrogen atom of at least one of the sulfonamide groups bound to hydrogen atoms or to an acyclic carbon atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/48—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups having nitrogen atoms of sulfonamide groups further bound to another hetero atom
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
    • C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
    • C07C311/50—Compounds containing any of the groups, X being a hetero atom, Y being any atom
    • C07C311/51—Y being a hydrogen or a carbon atom
    • 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
    • C07D213/78—Carbon atoms having three bonds to hetero atoms, with at the most one bond to halogen, e.g. ester or nitrile radicals
    • C07D213/81—Amides; Imides
    • 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

Definitions

  • the present invention relates to an amino fluorinating agent that introduces a protected amino group, and a method for producing an amino fluorinated product using the amino fluorinating agent.
  • Amino groups are highly reactive functional groups that play an important role in the activity of various organic compounds.
  • the primary amino group (-NH 2 ) is polar and forms hydrogen bonds between molecules and with other molecules, thereby playing an important role in maintaining the steric structure and intermolecular interactions.
  • Various aminating agents have been developed because useful organic compounds can be synthesized by aminating organic compounds. Limited to fluorobenzenesulfonimide (NFSI).
  • NFSI N-fluorobenzenesulfonimide
  • Non-Patent Document 3 Amino fluorination reaction (Non-Patent Document 3), which accompanies the cleavage of the carbon-carbon bond, aminating one carbon atom and introducing a fluorine atom into the other carbon atom, an amino group on the same carbon atom of a diazocarbonyl compound is used as an aminofluorinating agent in various reactions such as an aminofluorination reaction (Non-Patent Document 4) in which a fluorine atom is introduced simultaneously with
  • the present invention provides an amino fluorinating agent capable of introducing an amino group protected with a protective group that can be deprotected under relatively mild conditions to a wide range of substrates, and an amino group- and fluorine-containing
  • An object of the present invention is to provide a method for producing a compound.
  • the present inventors protect with a 2-nitrobenzenesulfonyl group (o-nosyl group) and a C 1-30 alkylsulfonyl group optionally having a halogen atom or a phenylsulfonyl group optionally having a substituent
  • o-nosyl group 2-nitrobenzenesulfonyl group
  • C 1-30 alkylsulfonyl group optionally having a halogen atom or a phenylsulfonyl group optionally having a substituent
  • G is -SO 2 R 1 , -CO-G 1 , -C(CH 3 )-Ph;
  • R 1 is a C 1-30 alkyl group optionally having a halogen atom; or a phenyl group optionally having substituents;
  • G 1 is a heteroaryl group optionally having substituents, or -CG 11 G 12 -G 13 ;
  • G 11 and G 12 are , each independently a hydrogen atom, a C 1-3 alkyl group, an alkoxy group, or a fluoroalkyl group;
  • G 13 is an optionally substituted phenyl group;
  • Ph is a phenyl group be]
  • R 1 is a C 1-30 alkyl group optionally having a halogen atom, or a phenyl group optionally having a substituent
  • a compound having at least one unsaturated bond is used as a substrate, and at least one unsaturated bond formed between carbon atoms in the substrate is removed using the amino fluorinating agent of [4].
  • a fluorine atom is introduced into one of the constituent carbon atoms, and the other carbon atom is represented by the following general formula (A1')
  • R 1 is a C 1-30 alkyl group optionally having a halogen atom, or a phenyl group optionally having a substituent.
  • a method for producing an amino group-containing compound, wherein a group represented by is introduced.
  • the substrate has the following general formula (B)
  • R 11 and R 21 are each independently a hydrogen atom, an optionally substituted C 1-30 aliphatic hydrocarbon group, an optionally substituted aryl group, or a heteroaryl group optionally having a substituent.
  • R 11 and R 21 are C 1-30 aliphatic hydrocarbon groups, these C 1-30 aliphatic hydrocarbon groups may be linked together to form a ring.
  • R 11 and R 21 are each independently a hydrogen atom, an optionally substituted C 1-30 aliphatic hydrocarbon group, an optionally substituted aryl group, or a heteroaryl group optionally having a substituent.
  • R 11 and R 21 are C 1-30 aliphatic hydrocarbon groups, these C 1-30 aliphatic hydrocarbon groups may be linked together to form a ring.
  • R 11 and R 21 are each independently a hydrogen atom, an optionally substituted C 1-30 aliphatic hydrocarbon group, an optionally substituted aryl group, or a heteroaryl group optionally having a substituent.
  • R 11 and R 21 are C 1-30 aliphatic hydrocarbon groups, these C 1-30 aliphatic hydrocarbon groups may be linked together to form a ring.
  • a method for producing a secondary amine comprising alkylating the nitrogen atom to which the Ns group is bound, followed by deprotecting the Ns group. [10] the following general formula (A0)
  • R 1 is a C 1-30 alkyl group optionally having a halogen atom, or a phenyl group optionally having a substituent
  • X is a hydrogen atom or a lithium atom.
  • the compounds according to the present invention are capable of reacting with various reactions similar to NFSI, with an amino group protected by an o-nosyl group and a C 1-30 alkylsulfonyl group or phenylsulfonyl group for a wide range of substrates having unsaturated bonds. can be introduced. Amino groups protected by these groups can be deprotected under milder conditions than NFSI, so the compounds are very useful as amino fluorinating agents.
  • C p1-p2 (p1 and p2 are positive integers satisfying p1 ⁇ p2) means a group having p1 to p2 carbon atoms.
  • a "C 1-30 alkyl group” is an alkyl group having 1 to 30 carbon atoms, and may be linear or branched.
  • a “C 2-30 alkyl group” is an alkyl group having 2 to 30 carbon atoms, and may be linear or branched.
  • C 1-30 alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert- pentyl group, hexyl group, isohexyl group, neohexyl group, heptyl group, octyl group, nonyl group, decyl group, undecyl group, dodecyl group, tridecyl group, tetradecyl group, pentadecyl group, hexadecyl group, heptadecyl group, octadecyl group, nonadecyl group , eicosyl group, heneicosyl group, docosyl group, tricosyl group, tetracosyl group, pentacosyl group, hexa
  • C 1-10 alkyl group is an alkyl group having 1 to 10 carbon atoms and may be linear or branched.
  • a “C 2-10 alkyl group” is an alkyl group having 2 to 10 carbon atoms, and may be linear or branched.
  • C 1-10 alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert- pentyl group, hexyl group, isohexyl group, neohexyl group, heptyl group, octyl group, nonyl group, decyl group and the like.
  • C 1-6 alkyl group is an alkyl group having 1 to 6 carbon atoms, and may be linear or branched.
  • Examples of C 1-6 alkyl groups include methyl, ethyl, propyl, isopropyl, butyl, isobutyl, sec-butyl, tert-butyl, pentyl, isopentyl, neopentyl, tert- pentyl group, hexyl group, isohexyl group, neohexyl group and the like.
  • C 1-3 alkyl group is an alkyl group having 1 to 3 carbon atoms and may be linear or branched.
  • Examples of C 1-3 alkyl groups include methyl, ethyl, propyl, isopropyl and the like.
  • a “C p1-p2 alkyl group having a substituent” means one or more, preferably one, hydrogen atoms bonded to the carbon atoms of the C p1-p2 alkyl group.
  • ⁇ 3 are groups substituted with other functional groups.
  • the substituents may be the same or different. Examples of the substituent include a halogen atom (fluorine atom, chlorine atom, bromine atom, or iodine atom), a C 6-14 aryl group optionally having a substituent, a cyano group, a nitro group, and the like.
  • C p1-p2 alkyl group having a substituent examples include, for example, a C 6-14 aryl-C 1-6 alkyl group.
  • a “C 6-14 aryl-C 1-6 alkyl group” is a group in which one hydrogen atom bonded to a carbon atom of a C 1-6 alkyl group is substituted with a C 6-14 aryl group.
  • the C 6-14 aryl group in the C 6-14 aryl-C 1-6 alkyl group can be exemplified by a phenyl group, a naphthyl group, an anthryl group, a 9-fluorenyl group and the like, and a phenyl group or a 9-fluorenyl group is particularly preferred.
  • the C 1-6 alkyl group in the C 6-14 aryl-C 1-6 alkyl group is preferably a C 1-4 alkyl group.
  • C 6-14 aryl-C 1-6 alkyl groups include benzyl group, diphenylmethyl group, triphenylmethyl group, 2-phenylethyl group, 9-anthrylmethyl group, 9-fluorenylmethyl group and the like. is mentioned.
  • C 1-30 aliphatic hydrocarbon group means optionally substituted C 1-30 alkyl group, optionally substituted C 2-30 All alkenyl groups and C 2-30 alkynyl groups optionally having substituents are included.
  • a “C 1-30 aliphatic hydrocarbon group” may be a straight chain, a branched chain, or a cyclic group.
  • Examples of the C 2-30 alkenyl group include groups in which at least one single bond between carbon atoms is a double bond among the groups listed for the C 2-30 alkyl group.
  • Examples of the C 2-30 alkynyl group include groups in which at least one single bond between carbon atoms is a triple bond among the groups listed for the C 2-30 alkyl group. More specifically, the C 2-30 alkenyl group includes vinyl group, propenyl group, 2-propenyl group, butenyl group, 1-methylpropenyl group, 2-methylpropenyl group, pentenyl group, hexenyl group, heptenyl group, octenyl group, nonenyl group, decenyl group, cyclobutenyl group, cyclopentenyl group, cyclohexenyl group and the like.
  • the C 2-30 alkynyl group includes ethynyl, propynyl, butynyl, 1-methylpropynyl, pentynyl, 2-methylbutynyl, hexynyl, heptynyl and octynyl groups.
  • a “C p1-p2 aliphatic hydrocarbon group having a substituent” means one of the hydrogen atoms bonded to the carbon atoms of the C p1-p2 aliphatic hydrocarbon group or A plurality, preferably 1 to 3, are groups substituted with other functional groups.
  • the substituents may be the same or different. Examples of the substituent include a halogen atom (fluorine atom, chlorine atom, bromine atom, or iodine atom), a C 6-14 aryl group optionally having a substituent, a cyano group, a nitro group, and the like.
  • C 1-30 alkoxy group refers to a group in which an oxygen atom is attached to the terminal end of a linear or branched alkyl group having 1 to 30 carbon atoms.
  • a "C 1-30 alkylthio group” refers to a group in which a sulfur atom is bonded to the terminal end of a linear or branched alkyl group having 1 to 30 carbon atoms. Examples of the linear or branched C 1-30 alkyl group in the C 1-30 alkoxy group or C 1-30 alkylthio group include those similar to the aforementioned C 1-30 alkyl group.
  • C 1-10 alkoxy group refers to a group in which an oxygen atom is bonded to the terminal end of a linear or branched alkyl group having 1 to 10 carbon atoms.
  • C 1-10 alkylthio group refers to a group in which a sulfur atom is bonded to the terminal end of a linear or branched alkyl group having 1 to 10 carbon atoms. Examples of the linear or branched C 1-10 alkyl group in the C 1-10 alkoxy group or C 1-10 alkylthio group include those similar to the aforementioned C 1-10 alkyl group.
  • C 1-6 alkoxy group refers to a group in which an oxygen atom is attached to the terminal end of a linear or branched alkyl group having 1 to 6 carbon atoms.
  • a “C 1-6 alkylthio group” refers to a group in which a sulfur atom is bonded to the terminal end of a linear or branched alkyl group having 1 to 6 carbon atoms. Examples of the linear or branched C 1-6 alkyl group in the C 1-6 alkoxy group or C 1-6 alkylthio group include those similar to the aforementioned C 1-6 alkyl group.
  • C 1-6 alkoxy groups include methoxy, ethoxy, propoxy, butoxy, tert-butoxy, pentyloxy, hexyloxy and the like.
  • C 1-6 alkylthio groups include methylthio, ethylthio, propylthio, butylthio, tert-butylthio, pentylthio, hexylthio and the like.
  • a “C p1-p2 alkoxy group having a substituent” means one or more, preferably one, hydrogen atoms bonded to the carbon atoms of the C p1-p2 alkoxy group. ⁇ 3 are groups substituted with other functional groups.
  • a “C p1-p2 alkylthio group having a substituent” means one or more, preferably one, hydrogen atoms bonded to the carbon atoms of the C p1-p2 alkylthio group. ⁇ 3 are groups substituted with other functional groups. When having two or more substituents, the substituents may be the same or different.
  • substituents examples include a halogen atom (fluorine atom, chlorine atom, bromine atom, or iodine atom), a C 6-14 aryl group optionally having a substituent, a cyano group, a nitro group, and the like.
  • a "C 6-14 aryl group” is an aromatic hydrocarbon group having 6 to 14 carbon atoms, and a C 6-12 aryl group is particularly preferred.
  • Examples of the C 6-14 aryl group include phenyl group (C 6 aryl group), naphthyl group, anthryl group, 9-fluorenyl group and the like, with phenyl group being particularly preferred.
  • the “optionally substituted C 6-14 aryl group” means one or more, preferably 1 to 1, hydrogen atoms bonded to the carbon atoms of the C 6-14 aryl group. Three are groups substituted with other functional groups. When having two or more substituents, the substituents may be the same or different. Such substituents include C 1-6 alkyl group, C 1-6 alkoxy group, methylenedioxy group (-O-CH 2 -O-), halogen atom (fluorine atom, chlorine atom, bromine atom or iodine atom ), and a nitro group.
  • Examples of “optionally substituted C 6-14 aryl group” include phenyl group, naphthyl group, anthryl group, 4-methylphenyl group, 2,6-dimethylphenyl group, 4-methoxyphenyl group, 2, 4-dimethoxyphenyl group, 3,4-dimethoxyphenyl group, 3-chlorophenyl group, 2-nitrophenyl group, 3-nitrophenyl group, 4-nitrophenyl group, 1,3-benzodioxol-5-yl group etc.
  • a "heteroaryl group” is a cyclic group having aromaticity, and the ring is composed of carbon atoms and atoms other than carbon atoms.
  • the heteroaryl group may be a group containing a nitrogen atom (nitrogen-containing heteroaryl group), a group containing an oxygen atom (oxygen-containing heteroaryl group), or a group containing a sulfur atom (sulfur-containing heteroaryl group).
  • nitrogen-containing heteroaryl group nitrogen-containing heteroaryl group
  • oxygen-containing heteroaryl group oxygen-containing heteroaryl group
  • sulfur-containing heteroaryl group sulfur-containing heteroaryl group
  • C 5-14 nitrogen-containing heteroaryl groups include pyrrolyl, imidazolyl, pyrazolyl, pyridyl, pyrazinyl, pyrimidinyl, pyridazinyl, indolyl, isoindolyl, benzimidazolyl, benzotriazolyl, quinolyl group, isoquinolyl group, quinazolyl group, carbazolyl group and the like.
  • the C 5-14 oxygen-containing heteroaryl group includes, for example, furanyl group, pyranyl group, benzopyranyl group, xanthenyl group and the like.
  • the C 5-14 sulfur-containing heteroaryl group includes, for example, a thienyl group and the like.
  • C 5-14 heteroaryl groups containing two or more heteroatoms include, for example, oxazolyl groups, isoxazolyl groups, thiazolyl groups, isothiazolyl groups, and the like.
  • a "heteroaryl group having a substituent” means one or more, preferably 1 to 3, hydrogen atoms bonded to the atoms constituting the aromatic ring of the heteroaryl group. is a group substituted with another functional group. When having two or more substituents, the substituents may be the same or different.
  • Such substituents include C 1-6 alkyl group, C 1-6 alkoxy group, C 1-6 alkylthio group, methylenedioxy group (-O-CH 2 -O-), halogen atom (fluorine atom, chlorine atom , bromine atom, or iodine atom), a trihalomethyl group, a cyano group, a nitro group, and the like.
  • aromatic group means an aryl group (aromatic hydrocarbon group) optionally having substituent(s) and a heteroaryl group (heterocyclic ring) optionally having substituent(s). formula group).
  • compound (n) means a compound represented by formula (n).
  • Solvents include methanol, 1,4-dioxane, diethyl ether, tetrahydrofuran (THF), dimethylsulfoxide (DMSO), dichloromethane (DCM), dichloroethane (DCE), acetonitrile (MeCN), triethylamine (TEA), benzene, toluene, Inert solvents such as N,N-dimethylformamide (DMF) and N,N-dimethylacetamide are included.
  • solvents such as N,N-dimethylformamide (DMF) and N,N-dimethylacetamide are included.
  • the compound according to the present invention is a compound represented by the following general formula (A).
  • G is -SO 2 R 1 , -CO-G 1 , -C(CH 3 )-Ph.
  • Ph is a phenyl group.
  • R 1 is a C 1-30 alkyl group optionally having a halogen atom, or a phenyl group optionally having a substituent.
  • R 1 specifically, the same group as R 1 in general formula (A1) described later can be used.
  • G 1 is an optionally substituted heteroaryl group or -CG 11 G 12 -G 13 .
  • G 11 and G 12 are each independently a hydrogen atom, a C 1-3 alkyl group, an alkoxy group or a fluoroalkyl group, and G 13 is a phenyl group optionally having a substituent.
  • the heteroaryl group is preferably a nitrogen-containing heteroaryl group, more preferably a C 5-14 nitrogen-containing heteroaryl group, and a pyridyl group. More preferred.
  • the alkoxy group is preferably a C 1-6 alkoxy group, more preferably a methoxy group, an ethoxy group or a propoxy group, and still more preferably a methoxy group.
  • the fluoroalkyl group is preferably a group in which one or more hydrogen atoms of a C 1-6 alkyl group is substituted with a fluorine atom, and a C 1-3 alkyl group.
  • a fluorine atom is more preferably a group in which at least one hydrogen atom of is substituted with a fluorine atom, more preferably a group in which one or more hydrogen atoms of a methyl group is substituted with a fluorine atom, and particularly preferably a trifluoromethyl group.
  • a phenyl group having a substituent is a group in which one or more, preferably 1 to 3, of the hydrogen atoms bonded to the carbon atoms of the phenyl group are substituted with other functional groups. . When having two or more substituents, the substituents may be the same or different.
  • G 13 is selected from the group consisting of a phenyl group, a C 1-6 alkyl group, a C 1-6 alkoxy group, a halogen atom (fluorine atom, chlorine atom, bromine atom or iodine atom), and a nitro group shell.
  • a phenyl group having one or more substituents is preferred, and a phenyl group or a phenyl group substituted with a C 1-6 alkyl group is more preferred.
  • -CG 11 G 12 -G 13 includes G 11 and G 12 each independently being a hydrogen atom or a methyl group. , a trifluoromethyl group, or a methoxy group, and G 13 is preferably a phenyl group substituted with an alkyl group, and G 11 and G 12 are each independently a hydrogen atom, a methyl group, or a trifluoromethyl group.
  • G 13 is a phenyl group substituted with a C 1-6 alkyl group
  • G 11 and G 12 are each independently a hydrogen atom, a methyl group, or a trifluoro More preferred is a methyl group or a methoxy group and G13 is a methylphenyl group.
  • R 1 is a C 1-30 alkyl group optionally having a halogen atom or a phenyl group optionally having a substituent.
  • R 1 is a C 1-30 alkyl group optionally having a halogen atom
  • R 1 is a C 1-6 alkyl group optionally having a halogen atom
  • An alkyl group is more preferable, and a methyl group, ethyl group, propyl group, isopropyl group, butyl group, isobutyl group, sec-butyl group, tert-butyl group, pentyl group, isopentyl group, neopentyl group, tert-pentyl group and hexyl group.
  • an isohexyl group and a neohexyl group are more preferred, and a methyl group is particularly preferred.
  • R 1 is a phenyl group optionally having substituents
  • R 1 is preferably a phenyl group optionally having substituents, and a C 1-6 alkyl group. , a C 1-6 alkoxy group, a halogen atom, and a phenyl group optionally having one or more substituents selected from the group consisting of a nitro group, more preferably a fluorine atom, a chlorine atom, and a nitro group.
  • a phenyl group optionally having one or more substituents selected from the group consisting of is more preferred, a nitrophenyl group is even more preferred, and an o-nitrophenyl group is particularly preferred.
  • Compound (A1) for example, by condensation reaction of a sulfonyl halide and sulfonamide to synthesize a sulfonimide, replace the hydrogen atom bonded to the nitrogen atom of the imide group with a lithium atom, and further replace the lithium atom with a fluorine atom. It can be synthesized by substituting atoms.
  • R 1 is the same as R 1 in general formula (A1).
  • compound (A1) can be produced by fluorinating a compound represented by general formula (A0) below.
  • R 1 is the same as R 1 in general formula (A1), and X is a hydrogen atom or a lithium atom.
  • the compound (8) is synthesized as described below, and the compound (8) is added with a sulfonyl compound, an acid chloride compound, a carboxylic acid group-containing compound, and a hydroxy group-containing compound. It can be produced by reacting etc.
  • Compound (A1) can be used as an active ingredient of an amino fluorinating agent in various reactions.
  • Compound (A1) can aminate carbon atoms in various organic compounds in the same manner as NFSI.
  • Organic compounds that can be used as substrates include, for example, compounds having unsaturated bonds such as alkenes, allyl compounds, alkynes, and aromatic compounds.
  • the unsaturated bond may be a bond formed between carbon atoms, or a bond between a carbon atom and an atom other than a carbon atom.
  • Compound (A1) can also use an organic compound containing a tricyclo ring as a substrate.
  • a compound having at least one unsaturated bond is used as a substrate, and compound (A1) is used as an aminofluorinating agent to form the unsaturated bond with respect to at least one unsaturated bond in the substrate.
  • a group represented by the following general formula (A1′) can be introduced to one carbon atom. At that time, a fluorine atom is introduced into the other carbon atom that constitutes the unsaturated bond.
  • R 1 is the same group as R 1 in general formula (A1), and a black circle represents a bond.
  • the group represented by general formula (A1') may be represented as "-[N]".
  • An amino group-containing compound can be produced by introducing a group represented by general formula (A1').
  • the group represented by the general formula (A1′) can be introduced to at least one of the two carbon atoms forming the unsaturated bond in the alkene.
  • R 11 and R 21 are each independently a hydrogen atom, an optionally substituted C 1-30 aliphatic hydrocarbon group, optionally substituted It is an aryl group or a heteroaryl group which may have a substituent. Further, when R 11 and R 21 are C 1-30 aliphatic hydrocarbon groups, these C 1-30 aliphatic hydrocarbon groups may be linked together to form a ring.
  • a group represented by the general formula (A1') is introduced into one carbon atom for amination, and a fluorine atom is introduced into the other carbon atom.
  • the compound obtained by fluorination is obtained by performing a 1,2-amino fluorination reaction using an alkene as a substrate and the compound (A1) in the presence of a catalyst such as a Pd catalyst.
  • the reaction conditions for the 1,2-amino fluorination reaction are the same reaction conditions as those for the 1,2-amino fluorination reaction by NFSI described in Example 3 below, Non-Patent Document 2, Non-Patent Document 6, etc. can be performed under appropriately modified conditions.
  • the compound into which the group represented by the general formula (A1′) has been introduced converts the group represented by the general formula (A1′) to a primary It can be an amino group.
  • an amino group-containing compound having a primary amino group introduced into one of the two carbon atoms constituting the unsaturated bond aminated by the compound (A1) can be produced.
  • NFSI NFSI
  • simple metals such as magnesium
  • strong acids such as trifluoromethanesulfonic acid (TfOH) and sulfuric acid.
  • TfOH trifluoromethanesulfonic acid
  • the deprotection reaction of the compound aminated by the compound (A1) involves a nucleophilic addition reaction to the o-nosyl group represented by the general formula (A1').
  • the deprotection reaction can be carried out under relatively mild conditions that do not require an elemental metal or a strong acid.
  • the compound (B) when used as the substrate, the compound (B) is reacted with the compound (A1-1) as an amino fluorinating agent, and then the Ns group represented by the following formula (D-1) is removed. Protection allows the production of primary amines.
  • the compound (B) when used as the substrate, the compound (B) is reacted with the compound (A1-2) as an amino fluorinating agent, and then the Ms group represented by the following formula (D-2) is removed.
  • Protect. A secondary amine can then be prepared by deprotecting the Ns group after alkylating the nitrogen atom to which the remaining Ns group is attached.
  • High resolution mass (HRMS) spectra were measured on a JEOL JMS-T100LP spectrometer in electrospray ionization time-of-flight (ESI-TOF) mode.
  • the unit of yield (%) described in the examples is mol%.
  • Example 1 A sulfonimide was synthesized by the following synthesis procedure.
  • N-fluoro-N-(2-nitrobenzenesulfonyl)methanesulfonamide was obtained from the sulfonimide (6.7 mmol) following the procedure described above. rice field. Purification by washing with hexanes gave N-fluoro-N-(2-nitrobenzenesulfonyl)methanesulfonamide (1.96 g, 99% yield) as a white solid.
  • a lithium salt was synthesized in the same manner as in Example 2.
  • a mixed solvent of 95 wt% acetonitrile/water (180-200 mL) the synthesized lithium salt solution of sulfonimide was added, stirred, and then cooled to 0°C.
  • a gas mixture of nitrogen gas mixed with 2% fluorine gas (volume percent) was introduced into the solution at a rate of 100 mL/min.
  • the insoluble solid was filtered and the filtrate was evaporated in vacuo to give a yellow solid as the crude product of N-fluoro-N-2-nitrobenzenesulfonamide (compound (8)).
  • the resulting crude product was added to dichloromethane (0.05 M), added with 200% by mass of silica gel, and stirred at room temperature for 1 day.
  • Example 4 Using the amino fluorinating agent synthesized in Example 2, an amino fluorinating reaction was carried out.
  • Example 5 Using the N-fluoro-N-(2-nitrobenzenesulfonyl)benzenesulfonamide synthesized in Example 3 as an aminofluorinating agent, an aminofluorinated styrene fluoride was synthesized.
  • Example 6 The amino fluorinating agent was synthesized by the synthetic procedure described in Example 2.
  • Example 7 Using the compound (1a) (N-fluoro-N-(2-nitrobenzenesulfonyl)methanesulfonamide) synthesized in Example 2 as an aminofluorinating agent, an aminofluorination reaction was carried out in the same manner as in Example 4. rice field.
  • Example 8 An aminofluorination reaction was carried out in the same manner as in Example 4 using the N-fluoro-N-(2,4'-dinitro)benzenesulfonimide synthesized in Example 6 as an aminofluorinating agent.
  • the present invention provides an amino fluorinating agent capable of deprotecting a substrate having an unsaturated bond under milder conditions than NFSI, and an amination reaction using the amino fluorinating agent.
  • amino groups can be easily introduced into a wide range of substrates such as alkenes, allyl compounds and aromatic compounds.

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

Abstract

La présente invention concerne un composé de formule générale (A) où G est -SO2R1, -CO-G1, ou -C(CH3)-Ph ; R1 est un groupe alkyle C1-30 pouvant posséder un atome d'halogène ou un groupe phényle pouvant posséder un substituant ; G1 est un groupe hétéroaryle pouvant posséder un substituant ou -CG11G12-G13 ; G11 et G12 sont chacun indépendamment un atome d'hydrogène, un groupe alkyle en C1-3, un groupe alcoxy ou un groupe fluoroalkyle ; G13 est un groupe phényle pouvant posséder un substituant ; et Ph est un groupe phényle].
PCT/JP2022/035395 2021-09-22 2022-09-22 Agent d'amino-fluoration et procédé de production d'un agent d'amino-fluoration WO2023048237A1 (fr)

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Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021060276A1 (fr) * 2019-09-24 2021-04-01 Ａｇｃ株式会社 Agent de fluoration et procédé de production de composés contenant du fluor
CN113072470A (zh) * 2021-03-30 2021-07-06 山东师范大学 一种n-乙腈基双苯磺酰亚胺衍生物及其制备方法与应用
WO2022025117A1 (fr) * 2020-07-29 2022-02-03 Ａｇｃ株式会社 Agent de fluoration et procédé de production de composés contenant du fluor

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2021060276A1 (fr) * 2019-09-24 2021-04-01 Ａｇｃ株式会社 Agent de fluoration et procédé de production de composés contenant du fluor
WO2022025117A1 (fr) * 2020-07-29 2022-02-03 Ａｇｃ株式会社 Agent de fluoration et procédé de production de composés contenant du fluor
CN113072470A (zh) * 2021-03-30 2021-07-06 山东师范大学 一种n-乙腈基双苯磺酰亚胺衍生物及其制备方法与应用

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
ADACHI AKIYA, AIKAWA KOHSUKE, ISHIBASHI YUICHIRO, NOZAKI KYOKO, OKAZOE TAKASHI: "Bench‐Stable Electrophilic Fluorinating Reagents for Highly Selective Mono‐ and Difluorination of Silyl Enol Ethers", CHEMISTRY - A EUROPEAN JOURNAL, JOHN WILEY & SONS, INC, DE, vol. 27, no. 46, 16 August 2021 (2021-08-16), DE, pages 11919 - 11925, XP093055071, ISSN: 0947-6539, DOI: 10.1002/chem.202101499 *
MODAK ATANU, PINTER EMILY N., COOK SILAS P.: "Copper-Catalyzed, N-Directed Csp 3 –H Trifluoromethylthiolation (−SCF 3 ) and Trifluoromethylselenation (−SeCF 3 )", JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, AMERICAN CHEMICAL SOCIETY, vol. 141, no. 46, 20 November 2019 (2019-11-20), pages 18405 - 18410, XP093055072, ISSN: 0002-7863, DOI: 10.1021/jacs.9b10316 *
YANG JIN-DONG, WANG YA, XUE XIAO-SONG, CHENG JIN-PEI: "A Systematic Evaluation of the N–F Bond Strength of Electrophilic N–F Reagents: Hints for Atomic Fluorine Donating Ability", THE JOURNAL OF ORGANIC CHEMISTRY, AMERICAN CHEMICAL SOCIETY, vol. 82, no. 8, 21 April 2017 (2017-04-21), pages 4129 - 4135, XP093055073, ISSN: 0022-3263, DOI: 10.1021/acs.joc.7b00036 *

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