CN106458901B - 用于制备稠合杂环化合物的方法 - Google Patents
用于制备稠合杂环化合物的方法 Download PDFInfo
- Publication number
- CN106458901B CN106458901B CN201580033836.4A CN201580033836A CN106458901B CN 106458901 B CN106458901 B CN 106458901B CN 201580033836 A CN201580033836 A CN 201580033836A CN 106458901 B CN106458901 B CN 106458901B
- Authority
- CN
- China
- Prior art keywords
- compound
- formula
- indicated
- optionally
- indicates
- 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
Links
- 238000000034 method Methods 0.000 title claims description 19
- 125000000623 heterocyclic group Chemical group 0.000 title description 4
- 150000001875 compounds Chemical class 0.000 claims abstract description 90
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 claims abstract description 26
- 239000002253 acid Substances 0.000 claims abstract description 20
- 125000005843 halogen group Chemical group 0.000 claims abstract description 12
- 150000003839 salts Chemical class 0.000 claims abstract description 9
- 229910052700 potassium Inorganic materials 0.000 claims abstract description 8
- 239000011591 potassium Substances 0.000 claims abstract description 8
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims abstract description 7
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 6
- 239000002904 solvent Substances 0.000 claims description 45
- 229910052799 carbon Inorganic materials 0.000 claims description 30
- 125000002947 alkylene group Chemical group 0.000 claims description 20
- 239000004215 Carbon black (E152) Substances 0.000 claims description 15
- 229930195733 hydrocarbon Natural products 0.000 claims description 15
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 14
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 14
- 125000004432 carbon atom Chemical group C* 0.000 claims description 11
- 238000002360 preparation method Methods 0.000 claims description 10
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 7
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 claims description 6
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 6
- 229910052744 lithium Inorganic materials 0.000 claims description 6
- 239000011734 sodium Substances 0.000 claims description 6
- 229910052708 sodium Inorganic materials 0.000 claims description 6
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 4
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 abstract description 3
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 abstract description 3
- -1 aminophenol compound Chemical class 0.000 description 48
- 239000002585 base Substances 0.000 description 35
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 32
- 238000006243 chemical reaction Methods 0.000 description 31
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 28
- 239000000203 mixture Substances 0.000 description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 21
- 239000011541 reaction mixture Substances 0.000 description 18
- 239000012299 nitrogen atmosphere Substances 0.000 description 16
- 239000007864 aqueous solution Substances 0.000 description 15
- 150000001721 carbon Chemical group 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 15
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 15
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
- 235000017557 sodium bicarbonate Nutrition 0.000 description 14
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 12
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 12
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
- ZUOUZKKEUPVFJK-UHFFFAOYSA-N diphenyl Chemical compound C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 description 10
- 238000005160 1H NMR spectroscopy Methods 0.000 description 9
- 239000003513 alkali Substances 0.000 description 9
- 238000003756 stirring Methods 0.000 description 9
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 8
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 8
- 239000000126 substance Substances 0.000 description 8
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 7
- 150000001408 amides Chemical class 0.000 description 7
- 125000006125 ethylsulfonyl group Chemical group 0.000 description 7
- 230000036571 hydration Effects 0.000 description 7
- 238000006703 hydration reaction Methods 0.000 description 7
- 238000002955 isolation Methods 0.000 description 7
- 238000010992 reflux Methods 0.000 description 7
- GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 6
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- IBBMAWULFFBRKK-UHFFFAOYSA-N picolinamide Chemical compound NC(=O)C1=CC=CC=N1 IBBMAWULFFBRKK-UHFFFAOYSA-N 0.000 description 6
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
- 235000010290 biphenyl Nutrition 0.000 description 5
- 239000004305 biphenyl Substances 0.000 description 5
- 230000018044 dehydration Effects 0.000 description 5
- 238000006297 dehydration reaction Methods 0.000 description 5
- 239000004210 ether based solvent Substances 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 238000010813 internal standard method Methods 0.000 description 5
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 description 4
- KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 4
- 208000005156 Dehydration Diseases 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- SIKJAQJRHWYJAI-UHFFFAOYSA-N Indole Chemical class C1=CC=C2NC=CC2=C1 SIKJAQJRHWYJAI-UHFFFAOYSA-N 0.000 description 4
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 4
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 4
- SRSXLGNVWSONIS-UHFFFAOYSA-N benzenesulfonic acid Chemical compound OS(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-N 0.000 description 4
- 229940092714 benzenesulfonic acid Drugs 0.000 description 4
- 238000004587 chromatography analysis Methods 0.000 description 4
- 229910052736 halogen Inorganic materials 0.000 description 4
- 150000002367 halogens Chemical class 0.000 description 4
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 4
- 239000007787 solid Substances 0.000 description 4
- ASDYMBLSNIBFMI-UHFFFAOYSA-N 2-amino-4-(trifluoromethylsulfonyl)phenol Chemical compound NC1=CC(S(=O)(=O)C(F)(F)F)=CC=C1O ASDYMBLSNIBFMI-UHFFFAOYSA-N 0.000 description 3
- BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 3
- WKRFAZABSKCRJU-UHFFFAOYSA-N 3-ethylsulfonylpyridine Chemical compound CCS(=O)(=O)C1=CC=CN=C1 WKRFAZABSKCRJU-UHFFFAOYSA-N 0.000 description 3
- DKPFZGUDAPQIHT-UHFFFAOYSA-N Butyl acetate Natural products CCCCOC(C)=O DKPFZGUDAPQIHT-UHFFFAOYSA-N 0.000 description 3
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 3
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 3
- 229910052783 alkali metal Inorganic materials 0.000 description 3
- RWGFKTVRMDUZSP-UHFFFAOYSA-N cumene Chemical compound CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 description 3
- JBTWLSYIZRCDFO-UHFFFAOYSA-N ethyl methyl carbonate Chemical compound CCOC(=O)OC JBTWLSYIZRCDFO-UHFFFAOYSA-N 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- FUZZWVXGSFPDMH-UHFFFAOYSA-N hexanoic acid Chemical compound CCCCCC(O)=O FUZZWVXGSFPDMH-UHFFFAOYSA-N 0.000 description 3
- 238000004128 high performance liquid chromatography Methods 0.000 description 3
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 3
- 229940071870 hydroiodic acid Drugs 0.000 description 3
- 239000007791 liquid phase Substances 0.000 description 3
- 150000007522 mineralic acids Chemical class 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 150000002825 nitriles Chemical class 0.000 description 3
- 229910000027 potassium carbonate Inorganic materials 0.000 description 3
- FVSKHRXBFJPNKK-UHFFFAOYSA-N propionitrile Chemical compound CCC#N FVSKHRXBFJPNKK-UHFFFAOYSA-N 0.000 description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 description 3
- 239000000243 solution Substances 0.000 description 3
- 229910052717 sulfur Inorganic materials 0.000 description 3
- 239000011593 sulfur Substances 0.000 description 3
- 125000006039 1-hexenyl group Chemical group 0.000 description 2
- KRIGAYSDVBBXLW-UHFFFAOYSA-N 2-chloro-3-ethylsulfonylpyridine Chemical compound CCS(=O)(=O)C1=CC=CN=C1Cl KRIGAYSDVBBXLW-UHFFFAOYSA-N 0.000 description 2
- ZRNSSRODJSSVEJ-UHFFFAOYSA-N 2-methylpentacosane Chemical compound CCCCCCCCCCCCCCCCCCCCCCCC(C)C ZRNSSRODJSSVEJ-UHFFFAOYSA-N 0.000 description 2
- 125000001494 2-propynyl group Chemical group [H]C#CC([H])([H])* 0.000 description 2
- SUDQAVKYUMPMKJ-UHFFFAOYSA-N 3-ethylsulfonylpyridine-2-carbonyl chloride Chemical compound CCS(=O)(=O)C1=CC=CN=C1C(Cl)=O SUDQAVKYUMPMKJ-UHFFFAOYSA-N 0.000 description 2
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
- BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical class C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 125000005605 benzo group Chemical group 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- 238000002425 crystallisation Methods 0.000 description 2
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 2
- 238000004821 distillation Methods 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 235000019441 ethanol Nutrition 0.000 description 2
- 239000011737 fluorine Substances 0.000 description 2
- GFAUNYMRSKVDJL-UHFFFAOYSA-N formyl chloride Chemical compound ClC=O GFAUNYMRSKVDJL-UHFFFAOYSA-N 0.000 description 2
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 150000002430 hydrocarbons Chemical class 0.000 description 2
- 150000007529 inorganic bases Chemical class 0.000 description 2
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- KWGKDLIKAYFUFQ-UHFFFAOYSA-M lithium chloride Chemical compound [Li+].[Cl-] KWGKDLIKAYFUFQ-UHFFFAOYSA-M 0.000 description 2
- AUHZEENZYGFFBQ-UHFFFAOYSA-N mesitylene Substances CC1=CC(C)=CC(C)=C1 AUHZEENZYGFFBQ-UHFFFAOYSA-N 0.000 description 2
- 125000001827 mesitylenyl group Chemical group [H]C1=C(C(*)=C(C([H])=C1C([H])([H])[H])C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- NBVXSUQYWXRMNV-UHFFFAOYSA-N monofluoromethane Natural products FC NBVXSUQYWXRMNV-UHFFFAOYSA-N 0.000 description 2
- 239000003960 organic solvent Substances 0.000 description 2
- CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 2
- PSAYJRPASWETSH-UHFFFAOYSA-N pyridine-2-carbonyl chloride Chemical compound ClC(=O)C1=CC=CC=N1 PSAYJRPASWETSH-UHFFFAOYSA-N 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- HXJUTPCZVOIRIF-UHFFFAOYSA-N sulfolane Chemical compound O=S1(=O)CCCC1 HXJUTPCZVOIRIF-UHFFFAOYSA-N 0.000 description 2
- 238000010189 synthetic method Methods 0.000 description 2
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 2
- 229920002554 vinyl polymer Polymers 0.000 description 2
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
- 125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
- 125000001340 2-chloroethyl group Chemical group [H]C([H])(Cl)C([H])([H])* 0.000 description 1
- 125000004777 2-fluoroethyl group Chemical group [H]C([H])(F)C([H])([H])* 0.000 description 1
- RWNISPVLLBWJBU-UHFFFAOYSA-N 2-sulfonyl-1h-pyridine Chemical compound O=S(=O)=C1C=CC=CN1 RWNISPVLLBWJBU-UHFFFAOYSA-N 0.000 description 1
- 125000000474 3-butynyl group Chemical group [H]C#CC([H])([H])C([H])([H])* 0.000 description 1
- JAGVCPHIQXGPHB-UHFFFAOYSA-N 3-ethylsulfanylpyridine Chemical compound CCSC1=CC=CN=C1 JAGVCPHIQXGPHB-UHFFFAOYSA-N 0.000 description 1
- OZFYEDXYDBRDRC-UHFFFAOYSA-N 3-ethylsulfonylpyridine-2-carboxylic acid Chemical compound CCS(=O)(=O)C1=CC=CN=C1C(O)=O OZFYEDXYDBRDRC-UHFFFAOYSA-N 0.000 description 1
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 1
- BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 description 1
- LSNNMFCWUKXFEE-UHFFFAOYSA-M Bisulfite Chemical compound OS([O-])=O LSNNMFCWUKXFEE-UHFFFAOYSA-M 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 description 1
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 description 1
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 1
- 239000005977 Ethylene Substances 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 1
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 1
- SIOXPEMLGUPBBT-UHFFFAOYSA-N Picolinic acid Natural products OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 1
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
- 239000005864 Sulphur Substances 0.000 description 1
- NBBVKIIJTYLUIA-UHFFFAOYSA-N [K].C(C)S(=O)(=O)C=1C(=NC=CC1)C(=O)O Chemical compound [K].C(C)S(=O)(=O)C=1C(=NC=CC1)C(=O)O NBBVKIIJTYLUIA-UHFFFAOYSA-N 0.000 description 1
- JBKPZZOWLLCKFG-UHFFFAOYSA-N [K].N1=CC=C(C=C1)C(=O)O Chemical compound [K].N1=CC=C(C=C1)C(=O)O JBKPZZOWLLCKFG-UHFFFAOYSA-N 0.000 description 1
- 239000003463 adsorbent Substances 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 1
- 125000003342 alkenyl group Chemical group 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 125000002029 aromatic hydrocarbon group Chemical group 0.000 description 1
- 239000012298 atmosphere Substances 0.000 description 1
- 150000003851 azoles Chemical class 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229920001429 chelating resin Polymers 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 125000001309 chloro group Chemical group Cl* 0.000 description 1
- 230000000052 comparative effect Effects 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 150000004816 dichlorobenzenes Chemical class 0.000 description 1
- 125000004772 dichloromethyl group Chemical group [H]C(Cl)(Cl)* 0.000 description 1
- 125000001028 difluoromethyl group Chemical group [H]C(F)(F)* 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- YVUBWJOBCFNMES-UHFFFAOYSA-N formamide;pyridine Chemical compound NC=O.C1=CC=NC=C1 YVUBWJOBCFNMES-UHFFFAOYSA-N 0.000 description 1
- PCHJSUWPFVWCPO-UHFFFAOYSA-N gold Chemical compound [Au] PCHJSUWPFVWCPO-UHFFFAOYSA-N 0.000 description 1
- 239000010931 gold Substances 0.000 description 1
- 229910052737 gold Inorganic materials 0.000 description 1
- 125000006343 heptafluoro propyl group Chemical group 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- VQTUBCCKSQIDNK-UHFFFAOYSA-N iso-butene Natural products CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 description 1
- XGZVUEUWXADBQD-UHFFFAOYSA-L lithium carbonate Chemical compound [Li+].[Li+].[O-]C([O-])=O XGZVUEUWXADBQD-UHFFFAOYSA-L 0.000 description 1
- 229910052808 lithium carbonate Inorganic materials 0.000 description 1
- HQRPHMAXFVUBJX-UHFFFAOYSA-M lithium;hydrogen carbonate Chemical compound [Li+].OC([O-])=O HQRPHMAXFVUBJX-UHFFFAOYSA-M 0.000 description 1
- UKVIEHSSVKSQBA-UHFFFAOYSA-N methane;palladium Chemical compound C.[Pd] UKVIEHSSVKSQBA-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 239000002808 molecular sieve Substances 0.000 description 1
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 1
- 125000006340 pentafluoro ethyl group Chemical group FC(F)(F)C(F)(F)* 0.000 description 1
- 238000012805 post-processing Methods 0.000 description 1
- 239000011736 potassium bicarbonate Substances 0.000 description 1
- 229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
- 239000000047 product Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- ATBIAJXSKNPHEI-UHFFFAOYSA-N pyridine-3-carbonyl chloride Chemical compound ClC(=O)C1=CC=CN=C1 ATBIAJXSKNPHEI-UHFFFAOYSA-N 0.000 description 1
- 150000004040 pyrrolidinones Chemical class 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 238000000638 solvent extraction Methods 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 150000003457 sulfones Chemical class 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- VXKWYPOMXBVZSJ-UHFFFAOYSA-N tetramethyltin Chemical compound C[Sn](C)(C)C VXKWYPOMXBVZSJ-UHFFFAOYSA-N 0.000 description 1
- 125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
- 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/04—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings directly linked by a ring-member-to-ring-member bond
-
- A—HUMAN NECESSITIES
- A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
- A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
- A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
- A01N43/34—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom
- A01N43/40—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having rings with one nitrogen atom as the only ring hetero atom six-membered rings
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C45/00—Injection moulding, i.e. forcing the required volume of moulding material through a nozzle into a closed mould; Apparatus therefor
- B29C45/17—Component parts, details or accessories; Auxiliary operations
- B29C45/26—Moulds
- B29C45/27—Sprue channels ; Runner channels or runner nozzles
- B29C45/28—Closure devices therefor
- B29C45/2806—Closure devices therefor consisting of needle valve systems
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B29—WORKING OF PLASTICS; WORKING OF SUBSTANCES IN A PLASTIC STATE IN GENERAL
- B29C—SHAPING OR JOINING OF PLASTICS; SHAPING OF MATERIAL IN A PLASTIC STATE, NOT OTHERWISE PROVIDED FOR; AFTER-TREATMENT OF THE SHAPED PRODUCTS, e.g. REPAIRING
- B29C45/00—Injection moulding, i.e. forcing the required volume of moulding material through a nozzle into a closed mould; Apparatus therefor
- B29C45/17—Component parts, details or accessories; Auxiliary operations
- B29C45/26—Moulds
- B29C45/27—Sprue channels ; Runner channels or runner nozzles
- B29C45/28—Closure devices therefor
- B29C45/2806—Closure devices therefor consisting of needle valve systems
- B29C45/281—Drive means therefor
-
- 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
- C07D213/62—Oxygen or sulfur atoms
-
- 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
-
- 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
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Life Sciences & Earth Sciences (AREA)
- Engineering & Computer Science (AREA)
- Manufacturing & Machinery (AREA)
- Mechanical Engineering (AREA)
- Dentistry (AREA)
- Zoology (AREA)
- Plant Pathology (AREA)
- Health & Medical Sciences (AREA)
- Agronomy & Crop Science (AREA)
- General Health & Medical Sciences (AREA)
- Wood Science & Technology (AREA)
- Pest Control & Pesticides (AREA)
- Environmental Sciences (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pyridine Compounds (AREA)
- Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
通过以下步骤制备由式(4)表示的化合物:步骤A,即,将由式(2)表示的化合物与亚硫酰氯反应,以获得由式(1)表示的化合物,其中R1表示乙基等,R表示卤素原子等,n表示0、1、2或3,且M表示钾等;步骤B,即,将由式(1)表示的化合物与由式(5)表示的化合物反应,以制备由式(3)表示的化合物或其酸式盐,其中A1表示氮原子或=CH‑,R5表示三氟甲基等,且m表示1或2;和步骤C,即,在酸的存在下将由式(3)表示的化合物或其酸式盐在100℃至180℃反应,以获得由式(4)表示的化合物。
Description
技术领域
本发明涉及用于制备稠合杂环化合物的方法。
背景技术
在WO 2013/018928公开的内容中,提到了包括2-(3-乙基硫烷基吡啶-2-基)-5-三氟甲基苯并唑在内的稠合杂环化合物针对有害生物具有出色的防治功效,并且,制备方法2提到了一种合成方法,在该合成方法中通过将氨基苯酚化合物与吡啶甲酰氯(pyridinecarboxylic chloride)化合物反应合成酰胺化合物,并随后对酰胺化合物进行闭环。
在Journal ofMedicinal Chemistry,29,860-862(1986)中,也提到了异烟酸钾与草酰氯反应制备异烟酰氯。
发明内容
本发明提供了一种用于制备由式(4)表示的化合物的方法:
其中
R1表示任选被卤代的具有1至6个碳原子的链烃基、或任选被卤代的具有3至6个碳原子的脂环烃基,
R各自独立地表示任选被卤代的具有1至6个碳原子的链烃基、或卤素原子,
R5表示任选被卤代的具有1至6个碳原子的链烃基、或任选被卤代的具有3至6个碳原子的脂环烃基,
A1表示氮原子或=CH-,
m表示1或2,且
n表示0、1、2或3。
本发明典型地如下。
[1]一种用于制备由式(4)表示的化合物的方法,所述方法包括:
步骤A,
将由式(2)表示的化合物
其中
R1表示任选被卤代的具有1至6个碳原子的链烃基、或任选被卤代的具有3至6个碳原子的脂环烃基,
R各自独立地表示任选被卤代的具有1至6个碳原子的链烃基、或卤素原子,n表示0、1、2或3,且M表示钠、钾或锂,
与亚硫酰氯反应以获得由式(1)表示的化合物(此后称为步骤A):
其中R1、R和n具有如上定义相同的含义;
步骤B,
将由式(1)表示的化合物与由式(5)表示的化合物反应
其中
A1表示氮原子或=CH-,
R5表示任选被卤代的具有1至6个碳原子的链烃基、或任选被卤代的具有3至6个碳原子的脂环烃基,且m表示1或2,以制备由式(3)表示的化合物(此后称为步骤B):
其中R1、R、R5、A1、m和n具有如上定义相同的含义;
和
步骤C,
在酸的存在下将由式(3)表示的化合物或其酸式盐在100℃至180℃反应,以获得由式(4)表示的化合物(此后称为步骤C):
其中R1、R、R5、A1、m和n具有如上定义相同的含义。
[2]根据[1]所述的制备方法,其中在步骤C中所述的酸是磺酸化合物。
[3]根据[1]所述的制备方法,其中在步骤C中所述的酸是对甲苯磺酸。
[4]根据[1]所述的制备方法,其中在步骤C中所述的酸是甲磺酸。
[5]一种用于制备由式(3)表示的化合物或其酸式盐的方法,所述方法包括:
步骤A,
将由式(2)表示的化合物
其中
R1表示任选被卤代的具有1至6个碳原子的链烃基、或任选被卤代的具有3至6个碳原子的脂环烃基,
R各自独立地表示任选被卤代的具有1至6个碳原子的链烃基、或卤素原子,n表示0、1、2或3,且M表示钠、钾或锂,与亚硫酰氯反应以获得由式(1)表示的化合物:
其中R1、R和n具有如上定义相同的含义;
和
步骤B,
将由式(1)表示的化合物与由式(5)表示的化合物反应
其中
A1表示氮原子或=CH-,
R5表示任选被卤代的具有1至6个碳原子的链烃基、或任选被卤
代的具有3至6个碳原子的脂环烃基,且m表示1或2,以制备由式(3)表示的化合物:
其中R1、R、R5、A1、m和n具有如上定义相同的含义。
[6]根据[1]至[5]中任一项所述的制备方法,其中在步骤B中所使用的溶剂包含醚溶剂。
[7]一种用于制备由式(1)表示的化合物的方法,所述方法包括:
步骤A,
将由式(2)表示的化合物
其中
R1表示任选被卤代的具有1至6个碳原子的链烃基、或任选被卤代的具有3至6个碳原子的脂环烃基,
R各自独立地表示任选被卤代的具有1至6个碳原子的链烃基、或卤素原子,n表示0、1、2或3,且M表示钠、钾或锂,与亚硫酰氯反应以获得由式(1)表示的化合物:
其中R1、R和n具有如上定义相同的含义。
本发明的实施方案
可以例如通过以下制备方法制备由式(1)表示的化合物、由式(3)表示的化合物和由式(4)表示的化合物。
在本发明中,卤素原子表示氟原子、氯原子、溴原子和碘原子。
在本发明中,具有1至6个碳原子的链烃基表示:具有1至6个碳原子的烷基,比如甲基、乙基、丙基、异丙基和己基;具有1至6个碳原子的烯基,比如乙烯基、1-丙烯基、2-丙烯基和1-己烯基;和具有1至6个碳原子的炔基,如乙炔基、炔丙基、1-戊炔基和1-己炔基。
在本发明中,任选被卤代的具有1至6个碳原子的链烃基的实例包括:任选地具有一个或多个卤素原子的C1-C6烷基,如甲基、乙基、异丙基、丁基、叔丁基、己基、氟甲基、氯甲基、溴甲基、碘甲基、二氟甲基、二氯甲基、三氟甲基、三氯甲基、2-氟乙基、2-氯乙基、2,2-二氟乙基、2,2,2-三氟乙基、五氟乙基和七氟丙基;
任选地具有一个或多个卤素原子的C2-C6烯基,如乙烯基、2-丙烯基、1-甲基乙烯基、2-甲基-1-丙烯基、3-丁烯基、1-己烯基、1,1-二氟烯丙基和五氟烯丙基;和
任选地具有一个或多个卤素原子的C2-C6炔基,比如乙炔基、炔丙基、3-丁炔基、1-己炔基和4,4,4-三氟-2-丁炔基。
在本发明中,具有3至6个碳原子的脂环烃基表示:具有3至6个碳原子的环烷基,如环丙基、环丁基和环己基;和具有3至6个碳原子的环烯基,如1-环己烯基和3-环己烯基。
在本发明中,磺酸化合物的实例包括:对甲苯磺酸、苯磺酸、甲磺酸和樟脑磺酸。
在本发明中,酰胺溶剂的实例包括:N,N-二甲基甲酰胺、N,N-二甲基乙酰胺和N-甲基吡咯烷酮。
在本发明中,醚溶剂的实例包括:四氢呋喃、乙二醇二甲醚、叔丁基甲基醚和1,4-二烷。
(步骤A)
由式(1)表示的化合物(在下文中称为化合物(1))可以通过将由式(2)表示的化合物(在下文中称为化合物(2))与亚硫酰氯反应来制备。
反应通常在溶剂中进行。在反应中使用的溶剂的实例包括:芳族烃溶剂,如甲苯、二甲苯、乙苯和氯苯;含卤素的脂族烃溶剂,如氯仿和二氯甲烷;醚溶剂,如四氢呋喃、乙二醇二甲醚、叔丁基甲基醚和1,4-二烷;酯溶剂,如乙酸乙酯和乙酸丁酯;腈溶剂,如乙腈和丙腈;芳族杂环溶剂,如吡啶;含硫化合物溶剂,如二甲亚砜和环丁砜;酰胺溶剂,如N,N-二甲基甲酰胺、N,N-二甲基乙酰胺和N-甲基吡咯烷酮;和它们的混合溶剂。溶剂优选为芳族烃溶剂、含卤素的脂族烃溶剂、酯溶剂、酰胺溶剂、和它们的混合物,更优选为芳族烃溶剂、酰胺溶剂、和它们的混合物,且最优选为N,N-二甲基甲酰胺。
基于1质量份的化合物(2),所用的溶剂的量通常为0至100质量份,且优选为1至20质量份。
在反应中,基于1摩尔的化合物(2),通常以1至15摩尔、且优选1至5摩尔的比例,使用亚硫酰氯。
反应的反应温度通常在0至150℃、且优选0至80℃的范围内。
反应的反应时间通常在0.1至24小时、且优选0.1至12小时的范围内。
在反应完成后,所得的化合物可以在通过蒸馏移除过量的亚硫酰氯后按原样用于步骤B,或者可以通过蒸馏纯化。通过利用过滤移除副产的氯化锂、氯化钠或氯化钾并将滤液浓缩,可以将化合物(1)分离。
化合物(2)可以通过将下式的2-吡啶甲酸与无机碱在溶剂中反应来制备:
所述无机碱比如碱金属氢氧化物(氢氧化钠、氢氧化钾和氢氧化锂)、碱金属碳酸盐(碳酸钠、碳酸钾和碳酸锂)和碱金属碳酸氢盐(碳酸氢钠、碳酸氢钾和碳酸氢锂),所述溶剂比如醇溶剂(甲醇、乙醇、2-丙醇等)。
(步骤B)
由式(3)表示的化合物(在下文中称为化合物(3))可以通过将化合物(1)与由式(5)表示的化合物(在下文中称为化合物(5))反应来制备。
反应通常在溶剂中进行。在反应中使用的溶剂的实例包括:芳族烃溶剂,如甲苯、二甲苯、乙苯和氯苯;含卤素的脂族烃溶剂,如氯仿和二氯甲烷;醚溶剂,如四氢呋喃、乙二醇二甲醚、叔丁基甲基醚和1,4-二烷;酯溶剂,如乙酸乙酯和乙酸丁酯;腈溶剂,如乙腈和丙腈;芳族杂环溶剂,如吡啶;含硫化合物溶剂,如二甲亚砜和环丁砜;酰胺溶剂,如N,N-二甲基甲酰胺、N,N-二甲基乙酰胺和N-甲基吡咯烷酮;和它们的混合溶剂。溶剂优选为含有醚溶剂的溶剂,且更优选为含有四氢呋喃的溶剂。
基于1质量份的化合物(1),所用的溶剂的量通常为1至100质量份,且优选为1至20质量份。
在反应中,任选地加入碱。碱的实例包括:碱金属碳酸盐,如碳酸钠和碳酸钾;碱金属碳酸氢盐,如碳酸氢钠和碳酸氢钾;和叔胺,如三乙胺、N,N-二异丙基乙胺、1,4-二氮杂双环[2.2.2]辛烷、1,8-二氮杂双环[5.4.0]十一碳烯、吡啶和4-二甲基氨基吡啶。
在反应中,基于1ml的化合物(5),通常以1至3摩尔的比例使用化合物(1)且通常以1至10摩尔的比例使用碱。优选地,通常以1至1.5摩尔的比例使用化合物(1)且通常以1至3摩尔的比例使用碱。
反应的反应温度通常在-20至100℃、且优选0至80℃的范围内。反应的反应时间通常在0.1至24小时、且优选0.1至12小时的范围内。
在反应完成后,在化合物(3)中形成盐酸盐,并且可以通过经过滤移除沉淀的晶体来将化合物(3)的盐酸盐分离,并随后该化合物可以按原样用于步骤C。当不经分离地用于步骤C时,化合物可以在用具有100℃以上的沸点的溶剂取代后用于步骤C。
通过进行后处理操作,如向反应混合物加入水,任选用碱如碳酸氢钠水溶液将混合物中和,并用有机溶剂萃取混合物,随后干燥并浓缩有机层,可以将化合物(3)分离。还可以通过色谱、重结晶等将分离化合物(3)进一步纯化。可以将化合物(3)以水合物的形式取出,且可以按原样用于步骤C。
可以通过与无机酸如硫酸、盐酸、氢溴酸和氢碘酸以及磺酸化合物如对甲苯磺酸、苯磺酸、甲磺酸和樟脑磺酸混合,将化合物(3)以盐的形式取出,并可以按原样用于步骤C。
(步骤C)
由式(4)表示的化合物(在下文中称为化合物(4))可以通过在酸的存在下将化合物(3)或其酸式盐在100℃至180℃反应来制备。
在反应中所用的酸的实例包括:无机酸如硫酸、盐酸、氢溴酸和氢碘酸;磺酸化合物如对甲苯磺酸、苯磺酸、甲磺酸和樟脑磺酸;或Amberlite(注册商标)酸性离子交换树脂。酸优选为磺酸化合物,且更优选对甲苯磺酸和甲磺酸。
反应通常在溶剂中进行。在反应中使用的溶剂的实例包括:芳族烃溶剂,如甲苯、二甲苯、乙苯、氯苯、异丙基苯(cumen)、均三甲苯和二氯苯;醚溶剂,如1,4-二烷;酯溶剂,如乙酸丁酯;腈溶剂,如丙腈;芳族杂环溶剂,如吡啶;含硫化合物溶剂,如二甲亚砜和环丁砜;酰胺溶剂,如N,N-二甲基甲酰胺、N,N-二甲基乙酰胺和N-甲基吡咯烷酮;和它们的混合溶剂。溶剂优选为芳族烃溶剂,且更优选为二甲苯和氯苯。
基于1质量份的化合物(3),所用的溶剂的量通常为1至100质量份,且优选为1至20质量份。
在反应中,基于1摩尔的化合物(3),通常以0.1摩尔至5摩尔、且优选0.5摩尔至3摩尔的比例使用酸。
反应的反应温度通常在100至180℃、且优选100至160℃的范围内。反应的反应时间通常在在0.1至48小时、且优选0.1至24小时的范围内。
在反应中,优选移除在原料中所含的水和在反应期间产生的水。移除方法的实例包括:其中通过使用Dean-Stark设备的共沸脱水等将水移除的方法,和其中通过使用脱水剂如分子筛、无水硫酸钠和无水硫酸镁将水移除的方法,并且移除方法优选为其中通过共沸脱水将水移除的方法。
在反应中,可以为了移除分解产物的目的加入吸附剂如活性碳、硅胶、和Celite(注册商标)。
在反应完成后,通过将反应混合物加入到水或碱的水溶液如碱金属碳酸盐(例如,Na2CO3、K2CO3)水溶液和碱金属碳酸氢盐(例如,NaHCO3、KHCO3)水溶液,将混合物用有机溶剂萃取,并且将有机层浓缩,通过过滤收集固体(该固体通过将反应混合物加入到水中产生的),或通过过滤收集在反应混合物中产生的固体,可以将化合物(4)分离。还可以通过色谱、重结晶等将分离化合物(4)进一步纯化。可以通过与无机酸如盐酸、氢溴酸和氢碘酸以及磺酸化合物如对甲苯磺酸、苯磺酸、甲磺酸和樟脑磺酸混合,将化合物(4)以盐的形式取出。
实施例
将借助实施例进一步描述本发明,但本发明不限于这些实施例。
实施例1
在氮气氛下,将0.50g的(3-乙基磺酰基)-2-吡啶甲酸钾、2.50g的二甲苯和0.01g的N,N-二甲基甲酰胺混合并加热至60℃,并随后在5小时内滴加0.35g的亚硫酰氯,随后在60℃搅拌4小时。向反应溶液中,加入异丁基胺,并通过内标法(内标物质;联苯)使用高效液相色谱进行定量测定,获得(3-乙基磺酰基)-2-吡啶甲酰氯,收率为95.1%。
实施例2
在氮气氛下,将25.00g的二甲苯、0.07g的N,N-二甲基甲酰胺和4.80g的亚硫酰氯混合并加热至60℃,并随后在5小时内加入5.00g的(3-乙基磺酰基)-2-吡啶甲酸钾,随后在60℃搅拌4小时。向反应溶液中,加入异丁基胺,并通过内标法(内标物质;联苯)使用高效液相色谱进行定量测定,获得(3-乙基磺酰基)-2-吡啶甲酰氯,收率为96.9%。
实施例3
通过以下方法制备2-氨基-4-(三氟甲基亚磺酰基)苯酚。
将5.0g的2-硝基-4-(三氟甲基亚磺酰基)苯酚、0.50g的钯-碳(Pd 5%),和65ml的乙醇的混合物在氢气氛下在35℃搅拌6小时。将冷却到室温的反应混合物经过Celite(注册商标)过滤,并添加水,随后用乙酸乙酯萃取。将有机层用水洗涤,经无水硫酸钠干燥,并随后在减压下浓缩。将所得的固体用氯仿洗涤,获得3.87g的2-氨基-4-(三氟甲基亚磺酰基)苯酚。
在氮气氛下,将1.80g的2-氨基-4-(三氟甲基亚磺酰基)苯酚和9.00g的四氢呋喃混合并冷却到0℃,并随后在一小时内滴加1.95g的(3-乙基磺酰基)-2-吡啶甲酰氯和3.90g的二甲苯的混合物,随后在0℃搅拌4小时。向反应混合物中,加入饱和的碳酸氢钠水溶液,并且将混合物用乙酸乙酯萃取,并且随后将有机层在减压下浓缩,获得3-乙基磺酰基-N-[2-羟基-5-(三氟甲基亚磺酰基)苯基]吡啶甲酰胺,收率为95.6%。
1H-NMR(DMSO-d6)δ:11.47(1H,brs),10.42(1H,s),8.97(1H,dd),8.74(1H,s),8.43(1H,d),7.88(1H,dd),7.58(1H,dd),7.25(1H,d),3.68(2H,q),1.18(3H,t)。
实施例4
在氮气氛下,将1.00g的3-乙基磺酰基-N-[2-羟基-5-(三氟甲基亚磺酰基)苯基]吡啶甲酰胺、0.66g的一水合对甲苯磺酸和5.00g的二甲苯的混合物在回流下在155℃脱水20小时。将冷却到室温的反应混合物加入到饱和的碳酸氢钠水溶液。在分离后,将5.00g的庚烷加入到有机层,并进行冷却结晶,获得2-(3-乙基磺酰基吡啶-2-基)-5-(三氟甲基亚磺酰基)苯并唑,收率为88.2%。
1H-NMR(CDCl3)δ:9.04(1H,dd),8.61(1H,dd),8.35(1H,d),7.96-7.86(2H,m),7.77(1H,dd),4.01(2H,q),1.44(3H,t)。
实施例5
在氮气氛下,将0.30g的3-乙基磺酰基-N-[2-羟基-5-(三氟甲基亚磺酰基)苯基]吡啶甲酰胺、0.20g的一水合对甲苯磺酸和1.50g的均三甲苯的混合物在回流下在180℃脱水7小时。将冷却到室温的反应混合物加入到饱和的碳酸氢钠水溶液。在分离后,将所得的有机层通过内标法(内标物质;联苯)使用高效液相色谱分析,获得2-(3-乙基磺酰基吡啶-2-基)-5-(三氟甲基亚磺酰基)苯并唑,收率为81.8%。
实施例6
在氮气氛下,将1.80g的2-氨基-4-(三氟甲磺酰)苯酚和9.00g的四氢呋喃混合。在冷却到0℃后,在一小时内滴加1.91g的(3-乙基磺酰基)-2-吡啶甲酰氯和3.82g的二甲苯的混合物,随后在0℃搅拌4小时。向反应混合物中,加入饱和的碳酸氢钠水溶液,并且混合物用乙酸乙酯萃取,并且随后将有机层在减压下浓缩,获得3-乙基磺酰基-N-[2-羟基-5-(三氟甲磺酰)苯基]吡啶甲酰胺,收率为96.7%。
1H-NMR(DMSO-d6)6:12.66(1H,brs),10.42(1H,s),8.97(1H,dd),8.85(1H,d),8.43(1H,dd),7.88(1H,dd),7.82(1H,dd),7.32(1H,d),3.68(2H,q),1.19(3H,t)。
实施例7
在氮气氛下,将10.00g的2-氨基-4-(三氟甲磺酰)苯酚和50.00g的四氢呋喃混合并冷却到0℃,并随后在一小时内滴加12.35g的(3-乙基磺酰基)-2-吡啶甲酰氯和27.00g的四氢呋喃的混合物,随后在0℃搅拌4小时。向反应混合物中,加入饱和的碳酸氢钠水溶液,并随后将混合物在减压下浓缩。将残余物用乙酸乙酯萃取,并将有机层在减压下浓缩,获得3-乙基磺酰基-N-[2-羟基-5-(三氟甲磺酰)苯基]吡啶甲酰胺,收率为93.4%。
实施例8
在氮气氛下,将1.00g的3-乙基磺酰基-N-[2-羟基-5-(三氟甲磺酰)苯基]吡啶甲酰胺、0.62g的一水合对甲苯磺酸和5.00g的二甲苯的混合物在回流下在155℃脱水15小时。将冷却到室温的反应混合物加入到饱和的碳酸氢钠水溶液。在分离后,将5.00g的庚烷加入到有机层,并进行冷却结晶,获得2-(3-乙基磺酰基吡啶-2-基)-5-(三氟甲磺酰)苯并唑,收率为86.5%。
1H-NMR(CDCl3)δ:9.05(1H,dd),8.61(1H,dd),8.59(1H,d),8.17(1H,dd),7.96(1H,d),7.80(1H,dd),3.98(2H,q),1.45(3H,t)。
实施例9
在氮气氛下,将2.70g的2-氨基-4-(三氟甲基亚磺酰基)苯酚和8.10g的四氢呋喃混合并冷却到0℃,并随后在4小时内滴加3.64g的(3-乙基磺酰基)-2-吡啶甲酰氯和3.64g的四氢呋喃的混合物,随后在0℃搅拌12小时。将反应混合物在减压下浓缩,获得6.21g的3-乙基磺酰基-N-[2-羟基-5-(三氟甲基亚磺酰基)苯基]吡啶甲酰胺盐酸盐,收率为96.7%。
1H-NMR(DMSO-d6)δ:12.56(1H,brs),10.40(1H,s),8.97(1H,dd),8.86(1H,d),8.44(1H,dd),7.88(1H,dd),7.81(1H,dd),7.42(1H,d),3.68(2H,q),1.20(3H,t)。
实施例10
在氮气氛下,将3.00g的3-乙基磺酰基-N-[2-羟基-5-(三氟甲基亚磺酰基)苯基]吡啶甲酰胺盐酸盐、1.24g的一水合对甲苯磺酸和15.00g的二甲苯的混合物在回流下在155℃脱水20小时。将冷却到室温的反应混合物加入到饱和的碳酸氢钠水溶液。在分离后,通过内标法(内标物质;联苯)使用高效液相色谱进行对所得的有机层的定量测定,获得2-(3-乙基磺酰基吡啶-2-基)-5-(三氟甲基亚磺酰基)苯并唑,收率为85.0%。
实施例11
在氮气氛下,将3.00g的2-氨基-4-(三氟甲基亚磺酰基)苯酚和12.00g的四氢呋喃混合并冷却到0℃,并随后在4小时内滴加4.11g的(3-乙基磺酰基)-2-吡啶甲酰氯和7.00g的二甲苯的混合物,随后在0℃搅拌12小时。将反应混合物在减压下浓缩,并且向所得的残余物中加入5.06g的一水合对甲苯磺酸和二甲苯16.90g的二甲苯的混合物,随后在回流下在155℃脱水24小时。将冷却到室温的反应混合物加入到饱和的碳酸氢钠水溶液。在分离后,通过内标法(内标物质;联苯)使用高效液相色谱进行对所得的有机层的定量测定,获得2-(3-乙基磺酰基吡啶-2-基)-5-(三氟甲基亚磺酰基)苯并唑,收率为79.4%。
实施例12
在氮气氛下,将4.33g的2-氨基-4-(三氟甲基亚磺酰基)苯酚和34.72g的四氢呋喃混合并冷却到0℃,并随后在一小时内滴加5.30g的(3-乙基磺酰基)-6-氯-2-吡啶甲酰氯和10.60g的四氢呋喃的混合物,随后在0℃搅拌4小时。向反应混合物中,加入饱和的碳酸氢钠水溶液,并且将混合物用乙酸乙酯萃取,并且随后将有机层在减压下浓缩,获得3-乙基磺酰基-N-[2-羟基-5-(三氟甲基亚磺酰基)苯基]吡啶甲酰胺,收率为99.2%。
1H-NMR(DMSO-d6)δ:11.55(1H,brs),10.45(1H,s),8.65(1H,s),8.38(1H,d),7.96(1H,d),7.57(1H,d),7.26(1H,d),3.84(2H,q),1.32(3H,t)。
实施例13
在氮气氛下,将1.00g的3-乙基磺酰基-6-氯-N-[2-羟基-5-(三氟甲基亚磺酰基)苯基]吡啶甲酰胺、0.74g的一水合对甲苯磺酸和5.21g的氯苯的混合物在回流下在140℃脱水8小时。将冷却到室温的反应混合物加入到饱和的碳酸氢钠水溶液。在分离后,将有机层浓缩,获得0.95g的2-(6-氯-3-乙基磺酰基吡啶-2-基)-5-(三氟甲基亚磺酰基)苯并唑。
1H-NMR(CDCl3)δ:8.53(1H,d),8.36(1H,d),7.94(1H,dd),7.89(1H,dd),7.76(1H,d),4.01(2H,q),1.44(3H,t)。
实施例14
在氮气氛下,将4.58g的2-氨基-4-(三氟甲磺酰)苯酚和36.82g的四氢呋喃混合并冷却到0℃,并随后在一小时内滴加5.30g的(3-乙基磺酰基)-6-氯-2-吡啶甲酰氯和10.60g的四氢呋喃的混合物,随后在0℃搅拌4小时。向反应混合物中,加入饱和的碳酸氢钠水溶液,并且将混合物用乙酸乙酯萃取,并且随后将有机层在减压下浓缩,获得3-乙基磺酰基-6-氯-N-[2-羟基-5-(三氟甲磺酰)苯基]吡啶甲酰胺,收率为98.4%。
1H-NMR(DMSO-d6)δ:10.77(1H,brs),9.97(1H,s),9.09(1H,s),8.49(1H,d),7.85(1H,d),7.77(1H,d),7.18(1H,d),3.80(2H,q),1.22(3H,t)。
实施例15
在氮气氛下,将1.01g的3-乙基磺酰基-6-氯-N-[2-羟基-5-(三氟甲磺酰)苯基]吡啶甲酰胺、0.72g的一水合对甲苯磺酸和5.32g的氯苯的混合物在回流下在140℃脱水8小时。将冷却到室温的反应混合物加入到饱和的碳酸氢钠水溶液。在分离后,将有机层浓缩,获得0.95g的2-(6-氯-3-乙基磺酰基吡啶-2-基)-5-(三氟甲磺酰)苯并唑。
1H-NMR(CDCl3)δ:8.59(1H,d),8.54(1H,d),8.18(1H,dd),7.98(1H,d),7.79(1H,d),3.98(2H,q),1.45(3H,t)。
比较例1
在氮气氛下,将3.00g的(3-乙基磺酰基)-2-吡啶甲酸、9.00g的甲苯和0.11g的N,N-二甲基甲酰胺混合并加热至60℃,并随后在5小时内滴加2.03g的亚硫酰氯,随后在60℃搅拌4小时。向反应溶液中,加入正丁醇,并使用高效液相色谱进行分析,获得(3-乙基磺酰基)-2-吡啶甲酰氯,收率为65.3%。
工业实用性
本发明提供了一种用于制备由式(4)表示的化合物的方法,该化合物针对有害生物具有出色防治功效。
Claims (7)
1.一种用于制备由式(4)表示的化合物的方法,所述方法包括:
步骤A,
将由式(2)表示的化合物
其中
R1表示任选被卤代的具有1至6个碳原子的链烃基、或任选被卤代的具有3至6个碳原子的脂环烃基,
R各自独立地表示任选被卤代的具有1至6个碳原子的链烃基、或卤素原子,n表示0、1、2或3,且M表示钠、钾或锂,
与亚硫酰氯反应以获得由式(1)表示的化合物:
其中R1、R和n具有与如上定义相同的含义;
步骤B,
将由式(1)表示的化合物与由式(5)表示的化合物反应
其中
A1表示氮原子或=CH-,
R5表示任选被卤代的具有1至6个碳原子的链烃基、或任选被卤代的具有3至6个碳原子的脂环烃基,且m表示1或2,
以制备由式(3)表示的化合物:
其中R1、R、R5、A1、m和n具有与如上定义相同的含义;
和
步骤C,
在酸的存在下将由式(3)表示的化合物或其酸式盐在100℃至180℃反应,以获得由式(4)表示的化合物:
其中R1、R、R5、A1、m和n具有与如上定义相同的含义。
2.根据权利要求1所述的制备方法,其中在步骤C中所述的酸是磺酸化合物。
3.根据权利要求1所述的制备方法,其中在步骤C中所述的酸是对甲苯磺酸。
4.根据权利要求1所述的制备方法,其中在步骤C中所述的酸是甲磺酸。
5.一种用于制备由式(3)表示的化合物或其酸式盐的方法,所述方法包括:
步骤A,
将由式(2)表示的化合物
其中
R1表示任选被卤代的具有1至6个碳原子的链烃基、或任选被卤代的具有3至6个碳原子的脂环烃基,
R各自独立地表示任选被卤代的具有1至6个碳原子的链烃基、或卤素原子,n表示0、1、2或3,且M表示钠、钾或锂,
与亚硫酰氯反应以获得由式(1)表示的化合物:
其中R1、R和n具有与如上定义相同的含义;
和
步骤B,
将由式(1)表示的化合物与由式(5)表示的化合物反应
其中
A1表示氮原子或=CH-,
R5表示任选被卤代的具有1至6个碳原子的链烃基、或任选被卤代的具有3至6个碳原子的脂环烃基,且m表示1或2,
以制备由式(3)表示的化合物:
其中R1、R、R5、A1、m和n具有与如上定义相同的含义。
6.根据权利要求1至5中任一项所述的制备方法,其中在步骤B中使用的溶剂包含醚溶剂。
7.一种用于制备由式(1)表示的化合物的方法,所述方法包括:
步骤A,
将由式(2)表示的化合物
其中
R1表示任选被卤代的具有1至6个碳原子的链烃基、或任选被卤代的具有3至6个碳原子的脂环烃基,
R各自独立地表示任选被卤代的具有1至6个碳原子的链烃基、或卤素原子,n表示0、1、2或3,且M表示钠、钾或锂,
与亚硫酰氯反应以获得由式(1)表示的化合物:
其中R1、R和n具有与如上定义相同的含义。
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP2014131037 | 2014-06-26 | ||
JP2014-131037 | 2014-06-26 | ||
PCT/JP2015/066126 WO2015198817A1 (en) | 2014-06-26 | 2015-05-28 | Method for producing fused heterocyclic compound |
Publications (2)
Publication Number | Publication Date |
---|---|
CN106458901A CN106458901A (zh) | 2017-02-22 |
CN106458901B true CN106458901B (zh) | 2019-01-18 |
Family
ID=53433231
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
CN201580033836.4A Active CN106458901B (zh) | 2014-06-26 | 2015-05-28 | 用于制备稠合杂环化合物的方法 |
Country Status (14)
Country | Link |
---|---|
US (1) | US10005766B2 (zh) |
EP (1) | EP3160962B1 (zh) |
JP (1) | JP6432452B2 (zh) |
KR (1) | KR102292928B1 (zh) |
CN (1) | CN106458901B (zh) |
AR (1) | AR100984A1 (zh) |
AU (1) | AU2015282127B2 (zh) |
DK (1) | DK3160962T3 (zh) |
ES (1) | ES2693320T3 (zh) |
IL (1) | IL249009B (zh) |
PH (1) | PH12016502334B1 (zh) |
RU (1) | RU2017102355A (zh) |
TW (1) | TWI657088B (zh) |
WO (1) | WO2015198817A1 (zh) |
Families Citing this family (19)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
AU2016307233B2 (en) | 2015-08-07 | 2020-12-24 | Bayer Cropscience Aktiengesellschaft | 2-(het)aryl-substituted condensed heterocyclic derivatives as pest control agents |
JP6871917B2 (ja) | 2015-09-28 | 2021-05-19 | バイエル・クロップサイエンス・アクチェンゲゼルシャフト | 有害生物防除剤としての2−(ヘタ)アリール−置換縮合二環式ヘテロ環誘導体 |
WO2017072039A1 (de) | 2015-10-26 | 2017-05-04 | Bayer Cropscience Aktiengesellschaft | Kondensierte bicyclische heterocyclen-derivate als schädlingsbekämpfungsmittel |
BR112018011830A2 (pt) * | 2015-12-16 | 2018-12-04 | Sumitomo Chemical Company, Limited | cristal de 2-(3-etanossulfonilpiridina-2-il)-5-(trifluorometanossulfonil)benzoxazol |
KR102627711B1 (ko) * | 2015-12-22 | 2024-01-22 | 수미토모 케미칼 컴퍼니 리미티드 | 벤즈옥사졸 화합물의 제조 방법 |
KR20180098410A (ko) | 2016-01-11 | 2018-09-03 | 바이엘 크롭사이언스 악티엔게젤샤프트 | 해충 방제제로서의 헤테로사이클렌 유도체 |
EP3415513A4 (en) | 2016-02-12 | 2019-07-17 | Sumitomo Chemical Company Limited | PROCESS FOR PRODUCING BENZOXAZOLE COMPOUND |
JP6581284B2 (ja) * | 2016-02-26 | 2019-09-25 | 日本農薬株式会社 | ベンゾオキサゾール化合物又はその塩類及び該化合物を含有する農園芸用殺虫剤並びにその使用方法 |
MX2019004032A (es) | 2016-10-06 | 2019-07-04 | Bayer Cropscience Ag | Derivados heterociclicos biciclicos condensados sustituidos por 2-(het)arilo como pesticidas. |
WO2018065288A1 (de) | 2016-10-07 | 2018-04-12 | Bayer Cropscience Aktiengesellschaft | 2-[2-phenyl-1-(sulfonylmethyl)vinyl]-imidazo[4,5-b]pyridin-derivate und verwandte verbindungen als schädlingsbekämpfungsmittel im pflanzenschutz |
KR102515694B1 (ko) | 2017-01-10 | 2023-03-29 | 바이엘 악티엔게젤샤프트 | 해충 방제제로서의 헤테로사이클 유도체 |
WO2018130443A1 (de) | 2017-01-10 | 2018-07-19 | Bayer Aktiengesellschaft | Heterocyclen-derivate als schädlingsbekämpfungsmittel |
MX2020013767A (es) | 2018-06-26 | 2021-03-02 | Bayer Ag | Derivados heterociclicos como plaguicidas. |
TWI818061B (zh) * | 2018-08-20 | 2023-10-11 | 日商住友化學股份有限公司 | 醯胺化合物及其用途 |
MX2021010215A (es) | 2019-02-26 | 2021-09-21 | Bayer Ag | Derivados de heterociclos biciclicos fusionados como pesticidas. |
US20220204499A1 (en) | 2019-02-26 | 2022-06-30 | Bayer Aktiengesellschaft | Condensed bicyclic heterocyclic derivatives as pest control agents |
EP4139304A1 (de) | 2020-04-21 | 2023-03-01 | Bayer Aktiengesellschaft | 2-(het)aryl-substituierte kondensierte heterocyclen-derivate als schädlingsbekämpfungsmittel |
US20230247994A1 (en) | 2020-07-02 | 2023-08-10 | Bayer Aktiengesellschaft | Heterocyclene derivatives as pest control agents |
CN117651702A (zh) | 2021-05-12 | 2024-03-05 | 拜耳公司 | 作为害虫防治剂的2-(杂)芳基取代的稠合杂环衍生物 |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE262883C (de) * | 1911-09-09 | 1913-07-25 | Eduard Kopetschni | Verfahren zur darstellung von säurechloriden der oxysäuren |
CN103717598A (zh) * | 2011-08-04 | 2014-04-09 | 住友化学株式会社 | 稠杂环化合物及其用于害虫防治的用途 |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
IL91083A (en) * | 1988-07-25 | 1993-04-04 | Ciba Geigy | Cyclohexanedione derivatives, their preparation and their use as herbicides |
MX370943B (es) * | 2012-12-27 | 2020-01-10 | Sumitomo Chemical Co | Compuestos de oxazol fusionados y uso de los mismos para el control de plagas. |
-
2015
- 2015-05-28 RU RU2017102355A patent/RU2017102355A/ru not_active Application Discontinuation
- 2015-05-28 WO PCT/JP2015/066126 patent/WO2015198817A1/en active Application Filing
- 2015-05-28 ES ES15729944.7T patent/ES2693320T3/es active Active
- 2015-05-28 CN CN201580033836.4A patent/CN106458901B/zh active Active
- 2015-05-28 EP EP15729944.7A patent/EP3160962B1/en not_active Not-in-force
- 2015-05-28 AU AU2015282127A patent/AU2015282127B2/en not_active Ceased
- 2015-05-28 US US15/320,907 patent/US10005766B2/en not_active Expired - Fee Related
- 2015-05-28 KR KR1020167035952A patent/KR102292928B1/ko active IP Right Grant
- 2015-05-28 DK DK15729944.7T patent/DK3160962T3/en active
- 2015-06-10 TW TW104118726A patent/TWI657088B/zh not_active IP Right Cessation
- 2015-06-22 JP JP2015124500A patent/JP6432452B2/ja active Active
- 2015-06-24 AR ARP150102026A patent/AR100984A1/es unknown
-
2016
- 2016-11-16 IL IL249009A patent/IL249009B/en active IP Right Grant
- 2016-11-23 PH PH12016502334A patent/PH12016502334B1/en unknown
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE262883C (de) * | 1911-09-09 | 1913-07-25 | Eduard Kopetschni | Verfahren zur darstellung von säurechloriden der oxysäuren |
CN103717598A (zh) * | 2011-08-04 | 2014-04-09 | 住友化学株式会社 | 稠杂环化合物及其用于害虫防治的用途 |
Also Published As
Publication number | Publication date |
---|---|
PH12016502334A1 (en) | 2017-02-13 |
RU2017102355A (ru) | 2018-07-26 |
PH12016502334B1 (en) | 2017-02-13 |
AU2015282127B2 (en) | 2018-12-20 |
DK3160962T3 (en) | 2018-12-03 |
TW201602101A (zh) | 2016-01-16 |
WO2015198817A1 (en) | 2015-12-30 |
US20170158682A1 (en) | 2017-06-08 |
EP3160962A1 (en) | 2017-05-03 |
AR100984A1 (es) | 2016-11-16 |
CN106458901A (zh) | 2017-02-22 |
IL249009A0 (en) | 2017-01-31 |
KR20170021256A (ko) | 2017-02-27 |
ES2693320T3 (es) | 2018-12-11 |
JP2016027019A (ja) | 2016-02-18 |
JP6432452B2 (ja) | 2018-12-05 |
KR102292928B1 (ko) | 2021-08-25 |
RU2017102355A3 (zh) | 2018-09-05 |
IL249009B (en) | 2019-03-31 |
TWI657088B (zh) | 2019-04-21 |
US10005766B2 (en) | 2018-06-26 |
AU2015282127A1 (en) | 2016-12-15 |
EP3160962B1 (en) | 2018-09-26 |
Similar Documents
Publication | Publication Date | Title |
---|---|---|
CN106458901B (zh) | 用于制备稠合杂环化合物的方法 | |
TWI658042B (zh) | 雜環化合物的合成 | |
CN104211618B (zh) | 制备吡咯化合物的方法 | |
TWI510451B (zh) | 具有hiv接合酶抑制活性的化合物之製造方法 | |
JP6995178B2 (ja) | 細胞毒性ベンゾジアゼピン誘導体の調製方法 | |
US8981105B2 (en) | Process of preparing a thrombin specific inhibitor | |
CN103874694B (zh) | 制备n-取代的1h-吡唑-5-甲酰氯化合物的方法 | |
JP6523334B2 (ja) | 置換サイクロセリンの調製のための方法 | |
TWI821237B (zh) | 用於製備可溶性鳥苷酸環化酶刺激劑之新穎方法及中間物 | |
CA3176061A1 (en) | Process for preparing a cot inhibitor compound | |
CN118439973A (zh) | 芳香族腈化合物的制造方法 | |
CN111704575B (zh) | 一种在无催化剂和无添加剂的条件下喹啉-2-硫代甲酰胺类化合物的合成方法 | |
CN103664959B (zh) | 一种五元双环胍类化合物的制备方法 | |
TW201829408A (zh) | 製備鹵化咪唑並吡啶衍生物之方法 | |
TWI702217B (zh) | 苯并唑化合物的製造方法 | |
CN108699049A (zh) | 用于制备苯并噁唑化合物的方法 | |
WO2014152768A1 (en) | Cyclohexanediamine compounds and methods for their preparation | |
WO2023214552A1 (ja) | トリフルオロメタンスルホニル化剤組成物、及び、トリフルオロメタンスルホニルオキシ化合物またはトリフルオロメタンスルホニル化合物の製造方法 | |
CN110156644A (zh) | 由Bunte盐合成N-硫基苄亚胺或其衍生物的方法 | |
JP2003221394A (ja) | キヌクリジン誘導体の製造方法 | |
JP2017105778A (ja) | 5−ピリジルオキシメチル−1,2−オキサゾール−3−イルピロリジン誘導体の製造方法 |
Legal Events
Date | Code | Title | Description |
---|---|---|---|
C06 | Publication | ||
PB01 | Publication | ||
C10 | Entry into substantive examination | ||
SE01 | Entry into force of request for substantive examination | ||
GR01 | Patent grant | ||
GR01 | Patent grant |