CN109796422A - A kind of light-catalyzed reaction is preparing the application in oxazolidine structural compounds - Google Patents
A kind of light-catalyzed reaction is preparing the application in oxazolidine structural compounds Download PDFInfo
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- CN109796422A CN109796422A CN201910224814.6A CN201910224814A CN109796422A CN 109796422 A CN109796422 A CN 109796422A CN 201910224814 A CN201910224814 A CN 201910224814A CN 109796422 A CN109796422 A CN 109796422A
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- heterocycle
- compound
- alkyl
- yuan
- aryl
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 56
- WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 title abstract description 7
- 238000006555 catalytic reaction Methods 0.000 title abstract description 3
- 238000006243 chemical reaction Methods 0.000 claims abstract description 86
- -1 silyl enol ether Chemical class 0.000 claims abstract description 73
- 238000000034 method Methods 0.000 claims abstract description 32
- 238000005286 illumination Methods 0.000 claims abstract description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 84
- 239000002585 base Substances 0.000 claims description 77
- IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 claims description 73
- 125000000623 heterocyclic group Chemical group 0.000 claims description 50
- 125000000217 alkyl group Chemical group 0.000 claims description 37
- 125000001072 heteroaryl group Chemical group 0.000 claims description 31
- 125000003118 aryl group Chemical group 0.000 claims description 29
- KKAJSJJFBSOMGS-UHFFFAOYSA-N 3,6-diamino-10-methylacridinium chloride Chemical group [Cl-].C1=C(N)C=C2[N+](C)=C(C=C(N)C=C3)C3=CC2=C1 KKAJSJJFBSOMGS-UHFFFAOYSA-N 0.000 claims description 26
- 229940023020 acriflavine Drugs 0.000 claims description 26
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 20
- 125000001424 substituent group Chemical group 0.000 claims description 20
- 229910052736 halogen Inorganic materials 0.000 claims description 19
- 150000002367 halogens Chemical class 0.000 claims description 19
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 19
- 125000002837 carbocyclic group Chemical group 0.000 claims description 18
- 125000003545 alkoxy group Chemical group 0.000 claims description 17
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 17
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 16
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 claims description 15
- 229910052799 carbon Inorganic materials 0.000 claims description 14
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
- 125000003342 alkenyl group Chemical group 0.000 claims description 13
- 125000000304 alkynyl group Chemical group 0.000 claims description 13
- 239000003513 alkali Substances 0.000 claims description 11
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 8
- 239000000758 substrate Substances 0.000 claims description 8
- 239000003054 catalyst Substances 0.000 claims description 7
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 claims description 7
- 239000001257 hydrogen Substances 0.000 claims description 7
- 229910052739 hydrogen Inorganic materials 0.000 claims description 7
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 125000004076 pyridyl group Chemical group 0.000 claims description 7
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 6
- 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 claims description 6
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 5
- 239000003795 chemical substances by application Substances 0.000 claims description 4
- 239000003814 drug Substances 0.000 claims description 4
- 239000000126 substance Substances 0.000 claims description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 4
- 229940079593 drug Drugs 0.000 claims description 3
- DCERHCFNWRGHLK-UHFFFAOYSA-N C[Si](C)C Chemical compound C[Si](C)C DCERHCFNWRGHLK-UHFFFAOYSA-N 0.000 claims description 2
- 150000001412 amines Chemical class 0.000 claims description 2
- 239000007810 chemical reaction solvent Substances 0.000 claims description 2
- 229940043279 diisopropylamine Drugs 0.000 claims description 2
- 239000003205 fragrance Substances 0.000 claims description 2
- 210000004209 hair Anatomy 0.000 claims description 2
- 239000000575 pesticide Substances 0.000 claims description 2
- ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 claims description 2
- FDPIMTJIUBPUKL-UHFFFAOYSA-N dimethylacetone Natural products CCC(=O)CC FDPIMTJIUBPUKL-UHFFFAOYSA-N 0.000 claims 1
- 230000003287 optical effect Effects 0.000 claims 1
- 125000000524 functional group Chemical group 0.000 abstract description 5
- 230000008569 process Effects 0.000 abstract description 4
- 238000010490 three component reaction Methods 0.000 abstract description 2
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 46
- 229910052740 iodine Inorganic materials 0.000 description 26
- ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 description 25
- 239000011630 iodine Substances 0.000 description 25
- 239000012973 diazabicyclooctane Substances 0.000 description 23
- 238000010898 silica gel chromatography Methods 0.000 description 22
- FANCTJAFZSYTIS-IQUVVAJASA-N (1r,3s,5z)-5-[(2e)-2-[(1r,3as,7ar)-7a-methyl-1-[(2r)-4-(phenylsulfonimidoyl)butan-2-yl]-2,3,3a,5,6,7-hexahydro-1h-inden-4-ylidene]ethylidene]-4-methylidenecyclohexane-1,3-diol Chemical compound C([C@@H](C)[C@@H]1[C@]2(CCCC(/[C@@H]2CC1)=C\C=C\1C([C@@H](O)C[C@H](O)C/1)=C)C)CS(=N)(=O)C1=CC=CC=C1 FANCTJAFZSYTIS-IQUVVAJASA-N 0.000 description 19
- 150000002084 enol ethers Chemical class 0.000 description 18
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical class CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 18
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 18
- 239000004575 stone Substances 0.000 description 17
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical class [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 13
- 125000004414 alkyl thio group Chemical group 0.000 description 7
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 238000005481 NMR spectroscopy Methods 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 125000004429 atom Chemical group 0.000 description 6
- 238000006073 displacement reaction Methods 0.000 description 6
- GVOISEJVFFIGQE-YCZSINBZSA-N n-[(1r,2s,5r)-5-[methyl(propan-2-yl)amino]-2-[(3s)-2-oxo-3-[[6-(trifluoromethyl)quinazolin-4-yl]amino]pyrrolidin-1-yl]cyclohexyl]acetamide Chemical compound CC(=O)N[C@@H]1C[C@H](N(C)C(C)C)CC[C@@H]1N1C(=O)[C@@H](NC=2C3=CC(=CC=C3N=CN=2)C(F)(F)F)CC1 GVOISEJVFFIGQE-YCZSINBZSA-N 0.000 description 6
- 239000003208 petroleum Substances 0.000 description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- OKKJLVBELUTLKV-MZCSYVLQSA-N Deuterated methanol Chemical compound [2H]OC([2H])([2H])[2H] OKKJLVBELUTLKV-MZCSYVLQSA-N 0.000 description 4
- 125000003282 alkyl amino group Chemical group 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 150000001721 carbon Chemical group 0.000 description 4
- 125000004432 carbon atom Chemical group C* 0.000 description 4
- 125000000000 cycloalkoxy group Chemical group 0.000 description 4
- 125000005366 cycloalkylthio group Chemical group 0.000 description 4
- 125000005842 heteroatom Chemical group 0.000 description 4
- 125000004415 heterocyclylalkyl group Chemical group 0.000 description 4
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 4
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 4
- JMANVNJQNLATNU-UHFFFAOYSA-N oxalonitrile Chemical compound N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 4
- 229910052760 oxygen Inorganic materials 0.000 description 4
- 239000001301 oxygen Substances 0.000 description 4
- ZJIJAJXFLBMLCK-UHFFFAOYSA-N perfluorohexane Chemical compound FC(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)C(F)(F)F ZJIJAJXFLBMLCK-UHFFFAOYSA-N 0.000 description 4
- 239000002904 solvent Substances 0.000 description 4
- LHJCZOXMCGQVDQ-UHFFFAOYSA-N tri(propan-2-yl)silyl trifluoromethanesulfonate Chemical compound CC(C)[Si](C(C)C)(C(C)C)OS(=O)(=O)C(F)(F)F LHJCZOXMCGQVDQ-UHFFFAOYSA-N 0.000 description 4
- 238000005160 1H NMR spectroscopy Methods 0.000 description 3
- KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 3
- BEXZJJQVPWJPOA-VOTSOKGWSA-N [(e)-hept-2-enyl] 6-methyl-4-(4-nitrophenyl)-2-oxo-3,4-dihydro-1h-pyrimidine-5-carboxylate Chemical compound CCCC\C=C\COC(=O)C1=C(C)NC(=O)NC1C1=CC=C([N+]([O-])=O)C=C1 BEXZJJQVPWJPOA-VOTSOKGWSA-N 0.000 description 3
- 150000007942 carboxylates Chemical class 0.000 description 3
- 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 3
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 3
- 230000000694 effects Effects 0.000 description 3
- 229910052731 fluorine Inorganic materials 0.000 description 3
- 125000002541 furyl group Chemical group 0.000 description 3
- 238000001819 mass spectrum Methods 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- 125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 3
- 229940002612 prodrug Drugs 0.000 description 3
- 239000000651 prodrug Substances 0.000 description 3
- CJQKFKQIFQGELD-UHFFFAOYSA-N propan-2-ylsilicon Chemical compound CC(C)[Si] CJQKFKQIFQGELD-UHFFFAOYSA-N 0.000 description 3
- 125000003226 pyrazolyl group Chemical group 0.000 description 3
- 125000005918 1,2-dimethylbutyl group Chemical group 0.000 description 2
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 2
- 238000004293 19F NMR spectroscopy Methods 0.000 description 2
- 125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 2
- 125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 2
- 125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- KWOLFJPFCHCOCG-UHFFFAOYSA-N Acetophenone Natural products CC(=O)C1=CC=CC=C1 KWOLFJPFCHCOCG-UHFFFAOYSA-N 0.000 description 2
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 2
- DGJMHKMYSDYOFP-MRXNPFEDSA-N C=CC(N(CCC1)C[C@@H]1N1N=C(C2=CN(CC(C3=CC=CC=C3)(F)F)N=N2)C2=C(N)N=CN=C12)=O Chemical compound C=CC(N(CCC1)C[C@@H]1N1N=C(C2=CN(CC(C3=CC=CC=C3)(F)F)N=N2)C2=C(N)N=CN=C12)=O DGJMHKMYSDYOFP-MRXNPFEDSA-N 0.000 description 2
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
- 239000005864 Sulphur Substances 0.000 description 2
- WLLIXJBWWFGEHT-UHFFFAOYSA-N [tert-butyl(dimethyl)silyl] trifluoromethanesulfonate Chemical compound CC(C)(C)[Si](C)(C)OS(=O)(=O)C(F)(F)F WLLIXJBWWFGEHT-UHFFFAOYSA-N 0.000 description 2
- 150000008062 acetophenones Chemical class 0.000 description 2
- 150000001335 aliphatic alkanes Chemical class 0.000 description 2
- 230000015572 biosynthetic process Effects 0.000 description 2
- 229910052794 bromium Inorganic materials 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- 239000000460 chlorine Substances 0.000 description 2
- 230000008878 coupling Effects 0.000 description 2
- 238000010168 coupling process Methods 0.000 description 2
- 238000005859 coupling reaction Methods 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 125000001153 fluoro group Chemical group F* 0.000 description 2
- 125000003709 fluoroalkyl group Chemical group 0.000 description 2
- 125000004836 hexamethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[*:1] 0.000 description 2
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 2
- 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 125000001971 neopentyl group Chemical group [H]C([*])([H])C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 125000005936 piperidyl group Chemical group 0.000 description 2
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 2
- 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 2
- 239000000741 silica gel Substances 0.000 description 2
- 229910002027 silica gel Inorganic materials 0.000 description 2
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 2
- 125000000335 thiazolyl group Chemical group 0.000 description 2
- FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 2
- HBENZIXOGRCSQN-VQWWACLZSA-N (1S,2S,6R,14R,15R,16R)-5-(cyclopropylmethyl)-16-[(2S)-2-hydroxy-3,3-dimethylpentan-2-yl]-15-methoxy-13-oxa-5-azahexacyclo[13.2.2.12,8.01,6.02,14.012,20]icosa-8(20),9,11-trien-11-ol Chemical compound N1([C@@H]2CC=3C4=C(C(=CC=3)O)O[C@H]3[C@@]5(OC)CC[C@@]2([C@@]43CC1)C[C@@H]5[C@](C)(O)C(C)(C)CC)CC1CC1 HBENZIXOGRCSQN-VQWWACLZSA-N 0.000 description 1
- PHDIJLFSKNMCMI-ITGJKDDRSA-N (3R,4S,5R,6R)-6-(hydroxymethyl)-4-(8-quinolin-6-yloxyoctoxy)oxane-2,3,5-triol Chemical compound OC[C@@H]1[C@H]([C@@H]([C@H](C(O1)O)O)OCCCCCCCCOC=1C=C2C=CC=NC2=CC=1)O PHDIJLFSKNMCMI-ITGJKDDRSA-N 0.000 description 1
- VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 description 1
- JNPGUXGVLNJQSQ-BGGMYYEUSA-M (e,3r,5s)-7-[4-(4-fluorophenyl)-1,2-di(propan-2-yl)pyrrol-3-yl]-3,5-dihydroxyhept-6-enoate Chemical compound CC(C)N1C(C(C)C)=C(\C=C\[C@@H](O)C[C@@H](O)CC([O-])=O)C(C=2C=CC(F)=CC=2)=C1 JNPGUXGVLNJQSQ-BGGMYYEUSA-M 0.000 description 1
- VAVHMEQFYYBAPR-ITWZMISCSA-N (e,3r,5s)-7-[4-(4-fluorophenyl)-1-phenyl-2-propan-2-ylpyrrol-3-yl]-3,5-dihydroxyhept-6-enoic acid Chemical compound CC(C)C1=C(\C=C\[C@@H](O)C[C@@H](O)CC(O)=O)C(C=2C=CC(F)=CC=2)=CN1C1=CC=CC=C1 VAVHMEQFYYBAPR-ITWZMISCSA-N 0.000 description 1
- QLVGHFBUSGYCCG-UHFFFAOYSA-N 2-amino-n-(1-cyano-2-phenylethyl)acetamide Chemical compound NCC(=O)NC(C#N)CC1=CC=CC=C1 QLVGHFBUSGYCCG-UHFFFAOYSA-N 0.000 description 1
- 125000003229 2-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- RSEBUVRVKCANEP-UHFFFAOYSA-N 2-pyrroline Chemical compound C1CC=CN1 RSEBUVRVKCANEP-UHFFFAOYSA-N 0.000 description 1
- 125000004337 3-ethylpentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000003469 3-methylhexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 description 1
- MWVKLRSIDOXBSE-UHFFFAOYSA-N 5-(1-piperidin-4-ylpyrazol-4-yl)-3-(6-pyrrolidin-1-yl-1,3-benzoxazol-2-yl)pyridin-2-amine Chemical compound NC1=NC=C(C2=CN(N=C2)C2CCNCC2)C=C1C(OC1=C2)=NC1=CC=C2N1CCCC1 MWVKLRSIDOXBSE-UHFFFAOYSA-N 0.000 description 1
- HIHOEGPXVVKJPP-JTQLQIEISA-N 5-fluoro-2-[[(1s)-1-(5-fluoropyridin-2-yl)ethyl]amino]-6-[(5-methyl-1h-pyrazol-3-yl)amino]pyridine-3-carbonitrile Chemical compound N([C@@H](C)C=1N=CC(F)=CC=1)C(C(=CC=1F)C#N)=NC=1NC=1C=C(C)NN=1 HIHOEGPXVVKJPP-JTQLQIEISA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical group [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 1
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 1
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Divinylene sulfide Natural products C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 1
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 1
- WRYCSMQKUKOKBP-UHFFFAOYSA-N Imidazolidine Chemical compound C1CNCN1 WRYCSMQKUKOKBP-UHFFFAOYSA-N 0.000 description 1
- XJTWGMHOQKGBDO-GOSISDBHSA-N N-[(3-Fluorophenyl)methyl]-1-[(1r)-1-Naphthalen-1-Ylethyl]piperidine-4-Carboxamide Chemical compound C1CN([C@H](C)C=2C3=CC=CC=C3C=CC=2)CCC1C(=O)NCC1=CC=CC(F)=C1 XJTWGMHOQKGBDO-GOSISDBHSA-N 0.000 description 1
- ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 description 1
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 1
- HGDWHTASNMRJMP-UHFFFAOYSA-N [1-(hydroxyamino)-1-oxo-5-(3-phenoxyphenyl)pentan-2-yl]phosphonic acid Chemical compound ONC(=O)C(P(O)(O)=O)CCCC1=CC=CC(OC=2C=CC=CC=2)=C1 HGDWHTASNMRJMP-UHFFFAOYSA-N 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001338 aliphatic hydrocarbons Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 239000004411 aluminium Substances 0.000 description 1
- 229910052782 aluminium Inorganic materials 0.000 description 1
- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
- 150000001414 amino alcohols Chemical class 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- 238000004458 analytical method Methods 0.000 description 1
- 230000008901 benefit Effects 0.000 description 1
- 230000000975 bioactive effect Effects 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- OSVHLUXLWQLPIY-KBAYOESNSA-N butyl 2-[(6aR,9R,10aR)-1-hydroxy-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-3-yl]-2-methylpropanoate Chemical compound C(CCC)OC(C(C)(C)C1=CC(=C2[C@H]3[C@H](C(OC2=C1)(C)C)CC[C@H](C3)CO)O)=O OSVHLUXLWQLPIY-KBAYOESNSA-N 0.000 description 1
- ZTAYJSRSQODHEO-UHFFFAOYSA-N butylsilicon Chemical group CCCC[Si] ZTAYJSRSQODHEO-UHFFFAOYSA-N 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 125000003262 carboxylic acid ester group Chemical group [H]C([H])([*:2])OC(=O)C([H])([H])[*:1] 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000004440 column chromatography Methods 0.000 description 1
- 229940125796 compound 3d Drugs 0.000 description 1
- 230000021615 conjugation Effects 0.000 description 1
- 229910052802 copper Inorganic materials 0.000 description 1
- 239000010949 copper Substances 0.000 description 1
- 150000001924 cycloalkanes Chemical class 0.000 description 1
- 125000000753 cycloalkyl group Chemical group 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001352 cyclobutyloxy group Chemical group C1(CCC1)O* 0.000 description 1
- 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000003678 cyclohexadienyl group Chemical group C1(=CC=CCC1)* 0.000 description 1
- 125000000596 cyclohexenyl group Chemical group C1(=CCCCC1)* 0.000 description 1
- 125000002933 cyclohexyloxy group Chemical group C1(CCCCC1)O* 0.000 description 1
- 125000000640 cyclooctyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 125000002433 cyclopentenyl group Chemical group C1(=CCCC1)* 0.000 description 1
- 125000002704 decyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 238000001514 detection method Methods 0.000 description 1
- 150000004985 diamines Chemical class 0.000 description 1
- 125000004852 dihydrofuranyl group Chemical group O1C(CC=C1)* 0.000 description 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
- AVAACINZEOAHHE-VFZPANTDSA-N doripenem Chemical compound C=1([C@H](C)[C@@H]2[C@H](C(N2C=1C(O)=O)=O)[C@H](O)C)S[C@@H]1CN[C@H](CNS(N)(=O)=O)C1 AVAACINZEOAHHE-VFZPANTDSA-N 0.000 description 1
- 239000011982 enantioselective catalyst Substances 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 239000011737 fluorine Substances 0.000 description 1
- 239000000499 gel Substances 0.000 description 1
- 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 1
- 125000002768 hydroxyalkyl group Chemical group 0.000 description 1
- 229910052738 indium Inorganic materials 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- JFOZKMSJYSPYLN-QHCPKHFHSA-N lifitegrast Chemical compound CS(=O)(=O)C1=CC=CC(C[C@H](NC(=O)C=2C(=C3CCN(CC3=CC=2Cl)C(=O)C=2C=C3OC=CC3=CC=2)Cl)C(O)=O)=C1 JFOZKMSJYSPYLN-QHCPKHFHSA-N 0.000 description 1
- 239000003863 metallic catalyst Substances 0.000 description 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
- 125000002757 morpholinyl group Chemical group 0.000 description 1
- SYSQUGFVNFXIIT-UHFFFAOYSA-N n-[4-(1,3-benzoxazol-2-yl)phenyl]-4-nitrobenzenesulfonamide Chemical class C1=CC([N+](=O)[O-])=CC=C1S(=O)(=O)NC1=CC=C(C=2OC3=CC=CC=C3N=2)C=C1 SYSQUGFVNFXIIT-UHFFFAOYSA-N 0.000 description 1
- 125000003136 n-heptyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 125000004433 nitrogen atom Chemical group N* 0.000 description 1
- QYSGYZVSCZSLHT-UHFFFAOYSA-N octafluoropropane Chemical compound FC(F)(F)C(F)(F)C(F)(F)F QYSGYZVSCZSLHT-UHFFFAOYSA-N 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 150000002896 organic halogen compounds Chemical class 0.000 description 1
- 229960004065 perflutren Drugs 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 125000003367 polycyclic group Chemical group 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 125000003373 pyrazinyl group Chemical group 0.000 description 1
- DNXIASIHZYFFRO-UHFFFAOYSA-N pyrazoline Chemical compound C1CN=NC1 DNXIASIHZYFFRO-UHFFFAOYSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 150000003254 radicals Chemical class 0.000 description 1
- 229920006395 saturated elastomer Polymers 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000007086 side reaction Methods 0.000 description 1
- 229920002379 silicone rubber Polymers 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 238000003786 synthesis reaction Methods 0.000 description 1
- 125000005958 tetrahydrothienyl group Chemical group 0.000 description 1
- CZDYPVPMEAXLPK-UHFFFAOYSA-N tetramethylsilane Chemical compound C[Si](C)(C)C CZDYPVPMEAXLPK-UHFFFAOYSA-N 0.000 description 1
- 150000004867 thiadiazoles Chemical class 0.000 description 1
- 125000001544 thienyl group Chemical group 0.000 description 1
- 125000004568 thiomorpholinyl group Chemical group 0.000 description 1
- 229930192474 thiophene Natural products 0.000 description 1
- RKBCYCFRFCNLTO-UHFFFAOYSA-N triisopropylamine Chemical compound CC(C)N(C(C)C)C(C)C RKBCYCFRFCNLTO-UHFFFAOYSA-N 0.000 description 1
- 125000000026 trimethylsilyl group Chemical group [H]C([H])([H])[Si]([*])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
- 230000017260 vegetative to reproductive phase transition of meristem Effects 0.000 description 1
Classifications
-
- 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
- Y02B—CLIMATE CHANGE MITIGATION TECHNOLOGIES RELATED TO BUILDINGS, e.g. HOUSING, HOUSE APPLIANCES OR RELATED END-USER APPLICATIONS
- Y02B20/00—Energy efficient lighting technologies, e.g. halogen lamps or gas discharge lamps
Landscapes
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Abstract
The present invention relates to a kind of light-catalyzed reactions to prepare the application in oxazolidine structural compounds, one kind is mainly provided under illumination condition, alkamine compound, silyl enol ether and three component reaction of perfluoroalkyl iodides prepare the reaction of oxazolidine structural compounds, this method process conditions are easy, it is easily operated, and yield is good, has wide functional group tolerance and good compatibility.
Description
Technical field
The invention belongs to chemical and medicine industry field, it is related under illumination condition, alkamine compound, silyl enol ether and perfluor alkane
Three component reaction of base iodine prepares the reaction of oxazolidine structural compounds, and this method process conditions are easy, easily operated, and yield is good
It is good, there is wide functional group tolerance and good compatibility.
Background technique
The N- heterocycle of saturation, the especially oxazolidine of highly functional cause the pass of people in academia and industry
Note because they often make specific drugs and important bioactive molecule have unexpected activity, and is also used extensively
In asymmetric syntheses.
Usually, substituted pro-drugs are constructed by ortho position amino alcohol direct alkylation, but due to numerous
The presence of trivial step and side reaction and keep its availability in the industry limited, for example, preparing specific organohalogen compounds and carbonyl
Based compound.On the other hand, it is by excessive metalcatalyzing or by the reaction of the free radical activation c h bond adjacent with N atom
It prepares pro-drugs and new thinking is provided, however, the use of the metallic catalyst of stoichiometry such as copper or tin is in certain journey
The implementation of strategies is also limited on degree.Prior, in the presence of apparent difficulty, i.e., these methods are constructing chiral quaternary carbon center
Just asymmetric catalyst is used, this is also still a difficult task.Therefore, what urgent need exploitation was new prepares pro-drugs
Method,
On the other hand, fluorine atom is introduced on organic molecule or the fluoro-alkyl of high substituted degree may be to organic molecule
Chemical and physical features generate deep effect.
Based on above content, the present invention provide it is a kind of using three component of visible light-inducing directly construct C-2 fluoroalkylation dislike
Method derived from oxazolidine.This method process conditions are easy, easily operated, and yield is good, with wide functional group tolerance and
Good compatibility, meanwhile, it can the very effective fluoro-alkyl that fluorine atom or high substituted degree are introduced in organic molecule.
Summary of the invention
The present invention provides a kind of preparation method of compound shown in formula 4,
Including under the conditions of photochemical catalyst, 1 compound of formula, 2 compound of formula and 3 compound of formula react 4 compound of acquisition formula
The step of,
Wherein, R1、R2Selected from hydrogen, alkyl, alkenyl, alkynyl, naphthenic base, heterocycle, aryl and heteroaryl, wherein described
Alkyl, alkenyl, alkynyl, naphthenic base, heterocycle, aryl and heteroaryl optionally by selected from alkyl, halogen, hydroxyl, amino, oxygroup,
Replaced one or more substituent groups in carboxyl, nitro, cyano, alkoxy, naphthenic base, heterocycle, aryl and heteroaryl, or
Person, R1And R2Carbon atom adjacent thereto is formed together 5 yuan to 10 yuan carbocyclic rings, heterocycle or condensed ring, preferably 6 yuan to 8 yuan carbocyclic rings, heterocycles
Or condensed ring, the carbocyclic ring, heterocycle or condensed ring optionally by selected from alkyl, halogen, hydroxyl, amino, oxygroup, carboxyl, nitro, cyano,
Replaced one or more substituent groups in alkoxy, naphthenic base, heterocycle, aryl and heteroaryl；
R3、R4、R5, R6Selected from hydrogen, alkyl, alkenyl, alkynyl, naphthenic base, heterocycle, aryl and heteroaryl, wherein described
Alkyl, alkenyl, alkynyl, naphthenic base, heterocycle, aryl and heteroaryl optionally by selected from alkyl, halogen, hydroxyl, amino, oxygroup,
Replaced one or more substituent groups in carboxyl, nitro, cyano, alkoxy, naphthenic base, heterocycle, aryl and heteroaryl,
Alternatively,
R5And R6Carbon atom adjacent thereto is formed together 5 yuan to 10 yuan carbocyclic rings, heterocycle or condensed ring, preferably 6 yuan to 8 yuan carbocyclic rings,
Heterocycle or condensed ring, the carbocyclic ring, heterocycle or condensed ring are optionally selected from alkyl, halogen, hydroxyl, amino, oxygroup, carboxyl, nitro, cyanogen
Replaced one or more substituent groups in base, alkoxy, naphthenic base, heterocycle, aryl and heteroaryl；
Alternatively,
R3And R6Carbon atom adjacent thereto is formed together 5 yuan to 10 yuan carbocyclic rings, heterocycle or condensed ring, preferably 6 yuan to 8 yuan carbocyclic rings,
Heterocycle or condensed ring, the carbocyclic ring, heterocycle or condensed ring are optionally selected from alkyl, halogen, hydroxyl, amino, oxygroup, carboxyl, nitro, cyanogen
Replaced one or more substituent groups in base, alkoxy, naphthenic base, heterocycle, aryl and heteroaryl；
P is selected from trimethyl silicon substrate, triisopropylsilyl or dimethyl tertiary butyl silicon substrate, preferably is selected from triisopropylsilyl；
N is the integer between 2~10.
Further, the photochemical catalyst is selected from acriflavine.
In some embodiments, it is the 0.1~1% of 3 compound mole of formula that light, which urges the dosage of agent, in the reaction, can
Think 0.1,0.2,0.3,0.4,0.5,0.6,0.7,0.8,0.9,1.0%.
In some embodiments, R described in the method for the invention1Selected from phenyl, naphthalene and pyridyl group, the benzene
Base, naphthalene and pyridyl group are optionally selected from C1-6Alkyl (such as methyl, ethyl or isopropyl), halogen (such as Cl, Br or I), hydroxyl (-
OH), amino (- NH2), carboxyl, nitro, cyano, C1-6Alkoxy (such as methoxyl group, ethyoxyl), C3-8Naphthenic base (such as cyclopropyl,
Cyclohexyl), C3-8One in heterocycle (such as pyrrole radicals, furyl), aryl (such as phenyl, naphthalene) and heteroaryl (such as pyridyl group)
Replaced a or multiple substituent groups.
In some embodiments, R described in the method for the invention2Selected from hydrogen.
In some embodiments, R1And R2Carbon atom adjacent thereto is formed together hexamethylene, and the hexamethylene is preferably by benzene
Replaced at least one of base, such as flowering structure is formed:
In some embodiments, R described in the method for the invention3、R4、R5, R6Selected from hydrogen, C1-6Alkyl (such as methyl,
Ethyl or isopropyl), C2-8Alkenyl, C2-8Alkynyl, C3-8Naphthenic base (such as cyclopropyl, cyclohexyl), C3-8Heterocycle (such as pyrrole radicals,
Furyl), aryl (such as phenyl, naphthalene) and heteroaryl (such as pyridyl group), wherein the alkyl, alkenyl, alkynyl, naphthenic base,
Heterocycle, aryl and heteroaryl optionally by selected from alkyl, halogen, hydroxyl, amino, oxygroup, carboxyl, nitro, cyano, alkoxy,
Replaced one or more substituent groups in naphthenic base, heterocycle, aryl and heteroaryl.
In some embodiments, the compound of formula 3 described in the method for the invention is selected from:
In some embodiments, the formula 4 is mixed body, and further, the dr of compound shown in the formula 4 is (non-right
Reflect the ratio of isomers) value is greater than or equal to 1:1, can be 1:1,2:1,3:1,4:1,5:1,6:1,7:1,8:1,9:1,10:
1,11:1,12:1,13:1,14:1,15:1,16:1,17:1,18:1,19:1,20:1 or higher, preferably greater than 20:1.
Further, the compound of formula 4 described in the method for the invention is selected from:
It on the other hand, further include alkali in reaction of the present invention, the presence of alkali is conducive to going on smoothly for reaction, and shows more
Effect.In some embodiments, the alkali be selected from triethylene diamine (DABCO), diisopropylamine (iPr2NH), preferred triethylene
Diamines.
Further, reaction solvent for use of the present invention is selected from acetonitrile, n,N-Dimethylformamide, acetone and tetrahydro furan
It mutters, preferably acetonitrile.
Light emitting diode can provide the light source of different frequency, wave band or watt, reaction of the present invention for illumination reaction
Light source used is from 4.5 watts of white light-emitting diodes.
In other embodiments, reaction temperature of the present invention is selected from 10~50 DEG C, can for 10,15,20,25,
30,35,40,45 and 50, preferably 15~30 DEG C.
In the preferred scheme, the method for the invention is included in photochemical catalyst acriflavine (Acriflavine), alkali
Triethylene diamine, under conditions of acetonitrile as solvents, 1 compound of formula, 2 compound of formula and 3 compound of formula react 4 compound of acquisition formula
The step of.
On the other hand, 2~8 equivalents of the dosage of alkali for 3 compound mole of formula, Ke Yiwei in the method for the invention
2,3,4,5,6,7 and 8 or the molar ratio of alkali and 3 compound of formula be 2:1~8:1.
In some embodiments, the molar ratio of 2 compound of the method for the invention Chinese style and 3 compound of formula be 1:1~
5:1 can be 1:1,2:1,3:1,4:1 and 5:1.
In some embodiments, the molar ratio of 3 compound of the method for the invention Chinese style and 1 compound of formula be 1:1~
2:1 can be 1:1,1.1:1,1.2:1,1.3:1,1.4:1,1.5:1,1.6:1,1.7:1,1.8:1,1.9:1 and 2:1.
Further, in preparation method of the present invention further include any in being filtered, washed, be concentrated, dry or purifying
Step obtains 4 compound of target product formula of purifying.
The present invention also provides a kind of preparation method of compound shown in formula 4,
Including, the step of 1 ' compound of formula is converted into 1 compound of formula,
Then under the conditions of photochemical catalyst, 1 compound of formula, 2 compound of formula and 3 compound of formula react 4 compound of acquisition formula
The step of,
Further, the method for 4 compound of preparation formula is " one pot of multistep processes ", i.e., in same reaction system, is during which not necessarily to
Subsequent reaction occurs for the step of isolated or purified, continuity,
In some embodiments, the reagent choosing of P functional group is provided in the step of 1 ' compound of formula is converted into 1 compound of formula
From but be not limited to tert-butyl dimethyl silyl triflate (TBSOTf), triisopropylsilyl triflate
(TIPSOTf) or Trimethylsilyl trifluoromethanesulfonate (TMSOTf).
In some embodiments, the molar ratio of 1 ' compound of formula and the reagent of offer P functional group is between 1:1~1:3
Arbitrary value, including but not limited to 1:1,1:1.5,1:2,1:2.5 and 1:3.
In some embodiments, solvent or used molten is not used in the step of 1 ' compound of formula is converted into 1 compound of formula
Agent is selected from but not limited to ethyl or tetrahydrofuran.
Further, in order to be conducive to the formation of silyl enol ether, there are also alkali in reaction, the alkali is selected from but not limited to three second
Amine, triisopropylamine or pyridine.
On the other hand, the formation temperature of the silyl enol ether is selected from 10~50 DEG C, can for 10,15,20,25,30,
35,40,45 and 50, preferably 15~30 DEG C.
Another aspect of the present invention provides a kind of method for preparing drug, fragrance and pesticide, including formula of the present invention 4
The preparation method of shown compound.
Unless stated to the contrary, the term used in the specification and in the claims has following meanings.
Term " alkyl " refers to saturated aliphatic hydrocarbons group, is the linear chain or branched chain group comprising 1 to 20 carbon atom, excellent
Select the alkyl containing 1 to 12 carbon atom.Non-limiting example includes methyl, ethyl, n-propyl, isopropyl, normal-butyl, isobutyl
Base, tert-butyl, sec-butyl, n-pentyl, 1,1- dimethyl propyl, 1,2- dimethyl propyl, 2,2- dimethyl propyl, 1- ethyl third
Base, 2- methyl butyl, 3- methyl butyl, n-hexyl, 1- Ethyl-2-Methyl propyl, 1,1,2- thmethylpropyl, 1,1- dimethyl
Butyl, 1,2- dimethylbutyl, 2,2- dimethylbutyl, 1,3- dimethylbutyl, 2- ethyl-butyl, 2- methyl amyl, 3- first
Base amyl, 4- methyl amyl, 2,3- dimethylbutyl, n-heptyl, 2- methylhexyl, 3- methylhexyl, 4- methylhexyl, 5- first
Base hexyl, 2,3- dimethyl amyl group, 2,4- dimethyl amyl group, 2,2- dimethyl amyl group, 3,3- dimethyl amyl group, 2- ethyl penta
Base, 3- ethylpentyl, n-octyl, 2,3- dimethylhexanyl, 2,4- dimethylhexanyl, 2,5- dimethylhexanyl, 2,2- dimethyl
Hexyl, 3,3- dimethylhexanyl, 4,4- dimethylhexanyl, 2- ethylhexyl, 3- ethylhexyl, 4- ethylhexyl, 2- methyl -2-
Ethylpentyl, 2- methyl -3- ethylpentyl, n-nonyl, 2- methyl -2- ethylhexyl, 2- methyl -3- ethylhexyl, 2,2- bis-
Ethylpentyl, positive decyl, 3,3- diethylhexyl, 2,2- diethylhexyl and its various branched isomers etc..More preferably
Low alkyl group containing 1 to 6 carbon atom, non-limiting embodiment include methyl, ethyl, n-propyl, isopropyl, normal-butyl,
Isobutyl group, tert-butyl, sec-butyl, n-pentyl, 1,1- dimethyl propyl, 1,2- dimethyl propyl, 2,2- dimethyl propyl, 1- second
Base propyl, 2- methyl butyl, 3- methyl butyl, n-hexyl, 1- Ethyl-2-Methyl propyl, 1,1,2- thmethylpropyl, 1,1- bis-
Methyl butyl, 1,2- dimethylbutyl, 2,2- dimethylbutyl, 1,3- dimethylbutyl, 2- ethyl-butyl, 2- methyl amyl,
3- methyl amyl, 4- methyl amyl, 2,3- dimethylbutyl etc..Alkyl can be it is substituted or non-substituted, when substituted,
Substituent group can be substituted on any workable tie point, and the substituent group is preferably one or more following groups,
Independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio group, alkyl amino, halogen, sulfydryl, hydroxyl, nitro, cyano, cycloalkanes
Base, Heterocyclylalkyl, aryl, heteroaryl, cycloalkyloxy, heterocyclylalkoxy groups, cycloalkylthio, heterocycle alkylthio group, oxo base, carboxyl or
Carboxylate.
Term " naphthenic base " refers to the unsaturated monocycle of saturation or part or polycyclic cyclic hydrocarbon substituent, cycloalkyl ring include 3 to
20 carbon atoms, preferably comprise 3 to 12 carbon atoms, more preferably include 3 to 6 carbon atoms.Monocyclic cycloalkyl it is non-limiting
Example includes cyclopropyl, cyclobutyl, cyclopenta, cyclopentenyl, cyclohexyl, cyclohexenyl group, cyclohexadienyl, suberyl, cycloheptyl
Trialkenyl, cyclooctyl etc.；Polycyclic naphthene base includes the naphthenic base of loop coil, condensed ring and bridged ring.
Term " heterocycle " refers to the unsaturated monocycle of saturation or part or polycyclic cyclic hydrocarbon substituent, and it includes 3 to 20 rings
Atom, wherein one or more annular atoms are the hetero atom selected from nitrogen, oxygen or S (O) m (wherein m is integer 0 to 2), but are not wrapped
The loop section of-O-O- ,-O-S- or-S-S- are included, remaining annular atom is carbon.3 to 12 annular atoms are preferably comprised, wherein 1~4
It is hetero atom；It more preferably include 3 to 6 annular atoms.The non-limiting example of monocyclic heterocycles base includes pyrrolidinyl, imidazolidine
Base, tetrahydrofuran base, tetrahydro-thienyl, glyoxalidine base, dihydrofuryl, pyrazoline base, pyrrolin base, piperidyl,
Piperazinyl, morpholinyl, thio-morpholinyl, high piperazine base etc., preferably piperidyl, pyrrolidinyl.Multiring heterocyclic includes loop coil, thick
The heterocycle of ring and bridged ring.
Term " aryl " refers to that 6 to 14 yuan of full carbon monocycles of the pi-electron system with conjugation or fused polycycle are (namely shared
The ring of adjacent carbon atoms pair) group, preferably 6 to 10 yuan, such as phenyl and naphthalene.
Aryl can be substituted or non-substituted, and when substituted, substituent group is preferably one or more following groups,
It is independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio group, alkyl amino, halogen, sulfydryl, hydroxyl, nitro, cyano, ring
Alkyl, Heterocyclylalkyl, aryl, heteroaryl, cycloalkyloxy, heterocyclylalkoxy groups, cycloalkylthio, heterocycle alkylthio group, carboxyl or carboxylic acid
Ester group, preferably phenyl.
Term " heteroaryl " refers to the heteroaromatic system comprising 1 to 4 hetero atom, 5 to 14 annular atoms, and wherein hetero atom selects
From oxygen, sulphur and nitrogen.Heteroaryl is preferably 5 to 12 yuan, such as imidazole radicals, furyl, thienyl, thiazolyl, pyrazolyl, oxazole
Base, pyrrole radicals, tetrazole radical, pyridyl group, pyrimidine radicals, thiadiazoles, pyrazinyl etc., preferably imidazole radicals, pyrazolyl, pyrimidine radicals or thiophene
Oxazolyl；More preferably pyrazolyl or thiazolyl.
Heteroaryl can be it is optionally replacing or non-substituted, when substituted, substituent group be preferably it is one or more with
Lower group, independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio group, alkyl amino, halogen, sulfydryl, hydroxyl, nitro,
Cyano, naphthenic base, Heterocyclylalkyl, aryl, heteroaryl, cycloalkyloxy, heterocyclylalkoxy groups, cycloalkylthio, heterocycle alkylthio group, carboxyl
Or carboxylate.
Term " alkoxy " refers to-O- (alkyl) and-O- (non-substituted naphthenic base), and wherein alkyl is as defined above.
The non-limiting example of alkoxy includes: methoxyl group, ethyoxyl, propoxyl group, butoxy, cyclopropyl oxygroup, cyclobutoxy group, penta oxygen of ring
Base, cyclohexyloxy.Alkoxy can be optionally replacing or non-substituted, and when substituted, substituent group is preferably one or more
A following group, independently selected from alkyl, alkenyl, alkynyl, alkoxy, alkylthio group, alkyl amino, halogen, sulfydryl, hydroxyl,
Nitro, cyano, naphthenic base, Heterocyclylalkyl, aryl, heteroaryl, cycloalkyloxy, heterocyclylalkoxy groups, cycloalkylthio, heterocycle alkane sulphur
Base, carboxyl or carboxylate.
Term " hydroxyalkyl " refers to the alkyl being optionally substituted by a hydroxyl group, and wherein alkyl is as defined above.
Term " halogenated alkyl " refers to the alkyl being optionally substituted by halogen, and wherein alkyl is as defined above.
Term " hydroxyl " refers to-OH group.
Term " halogen " refers to fluorine, chlorine, bromine or iodine.
Term " amino " refers to-NH2。
Term " cyano " refers to-CN.
Term " nitro " refers to-NO2。
" optional " or " optionally " mean event or environment described later can with but need not occur, which includes
The occasion that the event or environment occur or do not occur.For example, meaning that alkyl can be with " optionally by alkyl-substituted heterocyclic group "
But necessarily exist, the explanation include heterocyclic group by alkyl-substituted situation and heterocyclic group not by alkyl-substituted situation.
" substituted " refers to one or more hydrogen atoms in group, preferably at most 5, more preferably 1~3 hydrogen atom
Replaced independently of one another by the substituent group of respective number.Self-evident, substituent group is only in their possible chemical position, this
Field technical staff, which can determine in the case where not paying excessive make great efforts and (pass through experiment or theoretical), may or impossible take
Generation.It may be unstable when for example, amino or hydroxyl with free hydrogen are in conjunction with the carbon atom with unsaturated (such as olefinic) key
Fixed.
Agents useful for same or solvent of the present invention may be from commercial sources, or be prepared according to literature method.
The structure of compound is by nuclear magnetic resonance (NMR) or/and mass spectrum (MS) come what is determined.NMR is displaced (δ) with 10-6
(ppm) unit provides.The measurement of NMR is to use Bruker AVANCE-400 nuclear magnetic resonance spectrometer, and measurement solvent is deuterated dimethyl sulfoxide
(DMSO-d6), deuterated chloroform (CDCl3), deuterated methanol (CD3OD), inside it is designated as tetramethylsilane (TMS)；The measurement of MS is used
FINNIGAN LCQAd (ESI) mass spectrograph (manufacturer: Thermo, model: Finnigan LCQ advantage MAX).
Column chromatography is generally carrier or 100-200 mesh acidity or alkaline oxygen using 200~300 mesh silica gel of Yantai Huanghai Sea silica gel
Change aluminium.
Specific embodiment
The present invention is explained in detail below with reference to specific example, so that this hair is more fully understood in those skilled in the art
Bright specific example is only used to illustrate the technical scheme of the present invention, and does not limit the present invention in any way.
Embodiment 1:
Note: TIPS, triisopropylsilyl
In 5mL reaction flask, by silyl enol ether compound 1a (0.6mmol), perfluorinated butane base iodine 2a (0.9mmol), β-
The stirring in acetonitrile (2.0mL) of alkamine compound 3a (0.3mmol), alkali (1.2mmol) and variety classes photochemical catalyst is mixed
It closes, through N2Displacement is placed on irradiation under 4.5 watts of white light-emitting diodes for 3 times and is stirred to react 24 hours, and concentrated reaction solution leads to
The yield of NMR detection method analysis gained sample is crossed, dr (ratio of diastereoisomer) is greater than 20:1.Data are as shown in table 1 below:
Table 1
Note: b, by Isosorbide-5-Nitrae-dimethoxy benzene as internal standard compound,1H NMR detects alkyl indium and closes object；C, separation yield (silicon
Rubber column gel column purifying, ethyl acetate/petroleum ether mobile phase)；D, trimethylsilyl replace three isopropyl silicon substrates；E, three dislanyls replacement three
Isopropyl silicon substrate；Dimethyl tertiary butyl silicon substrate replaces three isopropyl silicon substrates.
Compound 4a characterize data:
IR (KBr) :=3331,2928,1679,1228,744,688cm-1
1H NMR (400MHz, CDCl3): δ=7.71-7.66 (m, 2H), 7.58-7.51 (m, 1H), 7.42-7.36 (m,
2H), 7.34 (d, J=7.3Hz, 1H), 7.27-7.24 (m, 1H), 7.20 (dd, J=7.3,1.2Hz, 1H), 6.93 (d, J=
7.4Hz, 1H), 5.11-5.01 (m, 1H), 4.96-4.84 (m, 1H), 3.88-3.72 (m, 2H), 2.99 (dd, J=17.7,
6.9Hz, 1H), 2.84 (d, J=13.8Hz, 1H), 2.62-2.48 (m, 1H) ppm.
19F NMR (376MHz, CDCl3): δ=- 80.76 (t, J=10.5Hz, 3F) ,-119.29-- 121.63 (m,
2F), -124.22 (t, J=4.7Hz, 2F) ppm.
13C NMR (100MHz, CDCl3): δ=196.9,141.1,140.4,137.2,133.5,128.8,128.8,
(128.3,127.5,125.1,124.8,98.3 t, JC-F=22.9Hz), 84.3,68.5,38.4 (m), 38.2ppm；
carbons corresponding to the C3F7group cannot be identified due to C-F
coupling.
HRMS(EI,m/z):calcd for C21H17F7NO2[M+H]+448.1142,found:448.1147.
Embodiment 2
In 5mL reaction flask, by silyl enol ether compound 1b (0.6mmol), perfluorinated butane base iodine 2a (0.9mmol), β-
Alkamine compound 3a (0.3mmol), triethylene diamine (DABCO) (134.5mg, 1.2mmol) and acriflavine (0.2mg,
It 0.0009mmol) is stirred in acetonitrile (2.0mL), through N2It replaces 3 times and is placed under 4.5 watts of white light-emitting diodes and shine
It penetrates and is stirred to react 36 hours, TLC is detected after completion of the reaction, and concentrated reaction solution is purified by silica gel column chromatography (ethyl acetate/stone
Oily ether is mobile phase) obtain sample, yield 68%.
IR (KBr) :=3403,2960,1615,1228,744,624cm-1.
1H NMR (400MHz, CDCl3): δ=7.54-7.48 (m, 2H), 7.29-7.21 (m, 3H), 7.19-7.15 (m,
1H), 7.11 (t, J=7.3Hz, 1H), 6.83 (d, J=7.4Hz, 1H), 5.02-4.91 (m, 1H), 4.80 (t, J=5.5Hz,
1H), 3.72-3.65 (m, 1H), 3.58 (d, J=4.7Hz, 1H), 2.97-2.85 (m, 1H), 2.72 (d, J=13.6Hz, 1H),
2.44 (d, J=17.7Hz, 1H) ppm.
19F NMR (376MHz, CDCl3): δ=- 80.78 (t, J=10.6Hz, 3F) ,-118.10-- 122.22 (m,
2F), -124.20 (dt, J=6.1,3.4Hz, 2F) ppm.
13C NMR (100MHz, CDCl3): δ=195.6,141.2,140.2,140.1,135.4,130.3,128.8,
(128.6,127.5,125.0,124.8,98.0 t, JC-F=24.3Hz), 84.4,68.3,38.8 (m), 38.1ppm；
carbons corresponding to the C3F7group cannot be identified due to C-F
coupling.
HRMS(EI,m/z):calcd for C21H16ClF7NO2[M+H]+482.0752,found:482.0758.
Embodiment 3
In 5mL reaction flask, by silyl enol ether compound 1c (0.6mmol), perfluorinated butane base iodine 2a (0.9mmol), β-
Alkamine compound 3a (0.3mmol), triethylene diamine (DABCO) (134.5mg, 1.2mmol) and acriflavine (0.2mg,
It 0.0009mmol) is stirred in acetonitrile (2.0mL), through N2It replaces 3 times and is placed under 4.5 watts of white light-emitting diodes and shine
It penetrates and is stirred to react 28 hours, TLC is detected after completion of the reaction, and concentrated reaction solution is purified by silica gel column chromatography (ethyl acetate/stone
Oily ether is mobile phase) obtain sample 4c, yield 55%.Dr (ratio of diastereoisomer) is greater than 20:1.
Embodiment 4
In 5mL reaction flask, by silyl enol ether compound 1d (0.6mmol), perfluorinated butane base iodine 2a (0.9mmol), β-
Alkamine compound 3a (0.3mmol), triethylene diamine (DABCO) (134.5mg, 1.2mmol) and acriflavine (0.2mg,
It 0.0009mmol) is stirred in acetonitrile (2.0mL), through N2It replaces 3 times and is placed under 4.5 watts of white light-emitting diodes and shine
It penetrates and is stirred to react 36 hours, TLC is detected after completion of the reaction, and concentrated reaction solution is purified by silica gel column chromatography (ethyl acetate/stone
Oily ether is mobile phase) obtain sample 4d, yield 63%.Dr (ratio of diastereoisomer) is greater than 20:1.
Embodiment 5
In 5mL reaction flask, by silyl enol ether compound 1e (0.6mmol), perfluorinated butane base iodine 2a (0.9mmol), β-
Alkamine compound 3a (0.3mmol), triethylene diamine (DABCO) (134.5mg, 1.2mmol) and acriflavine (0.2mg,
It 0.0009mmol) is stirred in acetonitrile (2.0mL), through N2It replaces 3 times and is placed under 4.5 watts of white light-emitting diodes and shine
It penetrates and is stirred to react 36 hours, TLC is detected after completion of the reaction, and concentrated reaction solution is purified by silica gel column chromatography (ethyl acetate/stone
Oily ether is mobile phase) obtain sample 4e, yield 60%.Dr (ratio of diastereoisomer) is greater than 20:1.
Embodiment 6
In 5mL reaction flask, by silyl enol ether compound 1f (0.6mmol), perfluorinated butane base iodine 2a (0.9mmol), β-
Alkamine compound 3a (0.3mmol), triethylene diamine (DABCO) (134.5mg, 1.2mmol) and acriflavine (0.2mg,
It 0.0009mmol) is stirred in acetonitrile (2.0mL), through N2It replaces 3 times and is placed under 4.5 watts of white light-emitting diodes and shine
It penetrates and is stirred to react 36 hours, TLC is detected after completion of the reaction, and concentrated reaction solution is purified by silica gel column chromatography (ethyl acetate/stone
Oily ether is mobile phase) obtain sample 4f, yield 51%.Dr (ratio of diastereoisomer) is greater than 20:1.
Embodiment 7
In 5mL reaction flask, by silyl enol ether compound 1g (0.6mmol), perfluorinated butane base iodine 2a (0.9mmol), β-
Alkamine compound 3a (0.3mmol), triethylene diamine (DABCO) (134.5mg, 1.2mmol) and acriflavine (0.2mg,
It 0.0009mmol) is stirred in acetonitrile (2.0mL), through N2It replaces 3 times and is placed under 4.5 watts of white light-emitting diodes and shine
It penetrates and is stirred to react 36 hours, TLC is detected after completion of the reaction, and concentrated reaction solution is purified by silica gel column chromatography (ethyl acetate/stone
Oily ether is mobile phase) obtain sample 4g, yield 53%.Dr (ratio of diastereoisomer) is greater than 20:1.
Embodiment 8
In 5mL reaction flask, by silyl enol ether compound 1h (0.6mmol), perfluorinated butane base iodine 2a (0.9mmol), β-
Alkamine compound 3a (0.3mmol), triethylene diamine (DABCO) (134.5mg, 1.2mmol) and acriflavine (0.2mg,
It 0.0009mmol) is stirred in acetonitrile (2.0mL), through N2It replaces 3 times and is placed under 4.5 watts of white light-emitting diodes and shine
It penetrates and is stirred to react 34 hours, TLC is detected after completion of the reaction, and concentrated reaction solution is purified by silica gel column chromatography (ethyl acetate/stone
Oily ether is mobile phase) obtain sample 4h, yield 54%.Dr (ratio of diastereoisomer) is greater than 20:1.
Embodiment 9
In 5mL reaction flask, by silyl enol ether compound 1i (0.6mmol), perfluorinated butane base iodine 2a (0.9mmol), β-
Alkamine compound 3a (0.3mmol), triethylene diamine (DABCO) (134.5mg, 1.2mmol) and acriflavine (0.2mg,
It 0.0009mmol) is stirred in acetonitrile (2.0mL), through N2It replaces 3 times and is placed under 4.5 watts of white light-emitting diodes and shine
It penetrates and is stirred to react 24 hours, TLC is detected after completion of the reaction, and concentrated reaction solution is purified by silica gel column chromatography (ethyl acetate/stone
Oily ether is mobile phase) obtain sample 4i, yield 48%.Dr (ratio of diastereoisomer) is greater than 20:1.
Embodiment 10
In 5mL reaction flask, by silyl enol ether compound 1j (0.6mmol), perfluorinated butane base iodine 2a (0.9mmol), β-
Alkamine compound 3a (0.3mmol), triethylene diamine (DABCO) (134.5mg, 1.2mmol) and acriflavine (0.2mg,
It 0.0009mmol) is stirred in acetonitrile (2.0mL), through N2It replaces 3 times and is placed under 4.5 watts of white light-emitting diodes and shine
It penetrates and is stirred to react 28 hours, TLC is detected after completion of the reaction, and concentrated reaction solution is purified by silica gel column chromatography (ethyl acetate/stone
Oily ether is mobile phase) obtain sample 4j, yield 48%.Dr (ratio of diastereoisomer) is greater than 20:1.
Embodiment 11
In 5mL reaction flask, by silyl enol ether compound 1k (0.6mmol), perfluorinated butane base iodine 2a (0.9mmol), β-
Alkamine compound 3a (0.3mmol), triethylene diamine (DABCO) (134.5mg, 1.2mmol) and acriflavine (0.2mg,
It 0.0009mmol) is stirred in acetonitrile (2.0mL), through N2It replaces 3 times and is placed under 4.5 watts of white light-emitting diodes and shine
It penetrates and is stirred to react 34 hours, TLC is detected after completion of the reaction, and concentrated reaction solution is purified by silica gel column chromatography (ethyl acetate/stone
Oily ether is mobile phase) obtain sample 4k, yield 59%.Dr (ratio of diastereoisomer) is greater than 20:1.
Embodiment 12
In 5mL reaction flask, by silyl enol ether compound 1l (0.6mmol), perfluorinated butane base iodine 2a (0.9mmol), β-
Alkamine compound 3a (0.3mmol), triethylene diamine (DABCO) (134.5mg, 1.2mmol) and acriflavine (0.2mg,
It 0.0009mmol) is stirred in acetonitrile (2.0mL), through N2It replaces 3 times and is placed under 4.5 watts of white light-emitting diodes and shine
It penetrates and is stirred to react 24 hours, TLC is detected after completion of the reaction, and concentrated reaction solution is purified by silica gel column chromatography (ethyl acetate/stone
Oily ether is mobile phase) obtain sample 4l, yield 65%.Dr (ratio of diastereoisomer) is greater than 20:1.
Embodiment 13
In 5mL reaction flask, by silyl enol ether compound 1m (0.6mmol), perfluorinated butane base iodine 2a (0.9mmol), β-
Alkamine compound 3a (0.3mmol), triethylene diamine (DABCO) (134.5mg, 1.2mmol) and acriflavine (0.2mg,
It 0.0009mmol) is stirred in acetonitrile (2.0mL), through N2It replaces 3 times and is placed under 4.5 watts of white light-emitting diodes and shine
It penetrates and is stirred to react 34 hours, TLC is detected after completion of the reaction, and concentrated reaction solution is purified by silica gel column chromatography (ethyl acetate/stone
Oily ether is mobile phase) obtain sample 4m, yield 56%.Dr (ratio of diastereoisomer) is greater than 20:1.
Embodiment 14
In 5mL reaction flask, by silyl enol ether compound 1o (0.6mmol), perfluorinated butane base iodine 2a (0.9mmol), β-
Alkamine compound 3a (0.3mmol), triethylene diamine (DABCO) (134.5mg, 1.2mmol) and acriflavine (0.2mg,
It 0.0009mmol) is stirred in acetonitrile (2.0mL), through N2It replaces 3 times and is placed under 4.5 watts of white light-emitting diodes and shine
It penetrates and is stirred to react 34 hours, TLC is detected after completion of the reaction, and concentrated reaction solution is purified by silica gel column chromatography (ethyl acetate/stone
Oily ether is mobile phase) sample 4o, yield 49% are obtained, dr is greater than 20:1.
Embodiment 15
In 5mL reaction flask, by silyl enol ether compound 1p (0.6mmol), perfluorinated butane base iodine 2a (0.9mmol), β-
Alkamine compound 3a (0.3mmol), triethylene diamine (DABCO) (134.5mg, 1.2mmol) and acriflavine (0.2mg,
It 0.0009mmol) is stirred in acetonitrile (2.0mL), through N2It replaces 3 times and is placed under 4.5 watts of white light-emitting diodes and shine
It penetrates and is stirred to react 48 hours, TLC is detected after completion of the reaction, and concentrated reaction solution is purified by silica gel column chromatography (ethyl acetate/stone
Oily ether is mobile phase) obtain sample 4p, yield 34%, dr=1:1.
Embodiment 16
In 5mL reaction flask, by silyl enol ether compound 1a (0.6mmol), perfluorinated butane base iodine 2a (0.9
Mmol), alkamine compound 3b (0.3mmol), triethylene diamine (DABCO) (134.5mg, 1.2mmol) and
Acriflavine (0.2mg, 0.0009mmol) is stirred in acetonitrile (2.0mL), through N2Displacement be placed on for 3 times 4.5 watts it is white
Irradiation is stirred to react 38 hours under color light emitting diode, and TLC is detected after completion of the reaction, concentrated reaction solution, through silica gel column chromatography
It purifies (ethyl acetate/petroleum ether is mobile phase) and obtains sample 4q, yield 59%.Dr is greater than 20:1.
Embodiment 17
In 5mL reaction flask, by silyl enol ether compound 1a (0.6mmol), perfluorinated butane base iodine 2a (0.9
Mmol), alkamine compound 3c (0.3mmol), triethylene diamine (DABCO) (134.5mg, 1.2mmol) and
Acriflavine (0.2mg, 0.0009mmol) is stirred in acetonitrile (2.0mL), through N2Displacement be placed on for 3 times 4.5 watts it is white
Irradiation is stirred to react 38 hours under color light emitting diode, and TLC is detected after completion of the reaction, concentrated reaction solution, through silica gel column chromatography
It purifies (ethyl acetate/petroleum ether is mobile phase) and obtains sample 4r, yield 59%.Dr is greater than 20:1.
Embodiment 18
In 5mL reaction flask, by silyl enol ether compound 1a (0.6mmol), perfluorinated butane base iodine 2a (0.9
Mmol), alkamine compound 3d (0.3mmol), triethylene diamine (DABCO) (134.5mg, 1.2mmol) and
Acriflavine (0.2mg, 0.0009mmol) is stirred in acetonitrile (2.0mL), through N2Displacement be placed on for 3 times 4.5 watts it is white
Irradiation is stirred to react 24 hours under color light emitting diode, and TLC is detected after completion of the reaction, concentrated reaction solution, through silica gel column chromatography
It purifies (ethyl acetate/petroleum ether is mobile phase) and obtains sample 4s, yield 69%.Dr is greater than 20:1.
Embodiment 18
In 5mL reaction flask, by silyl enol ether compound 1a (0.6mmol), perfluoropropane base iodine 2b (0.9mmol), ammonia
Base alcoholic compound 3a (0.3mmol), triethylene diamine (DABCO) (134.5mg, 1.2mmol) and acriflavine (0.2mg,
It 0.0009mmol) is stirred in acetonitrile (2.0mL), through N2It replaces 3 times and is placed under 4.5 watts of white light-emitting diodes and shine
It penetrates and is stirred to react 48 hours, TLC is detected after completion of the reaction, and concentrated reaction solution is purified by silica gel column chromatography (ethyl acetate/stone
Oily ether is mobile phase) obtain sample 4t, yield 55%.Dr is greater than 20:1.
Embodiment 18
In 5mL reaction flask, by silyl enol ether compound 1a (0.6mmol), perfluoro-n-hexane base iodine 2c (0.9mmol),
Alkamine compound 3a (0.3mmol), triethylene diamine (DABCO) (134.5mg, 1.2mmol) and acriflavine (0.2mg,
It 0.0009mmol) is stirred in acetonitrile (2.0mL), through N2It replaces 3 times and is placed under 4.5 watts of white light-emitting diodes and shine
It penetrates and is stirred to react 48 hours, TLC is detected after completion of the reaction, and concentrated reaction solution is purified by silica gel column chromatography (ethyl acetate/stone
Oily ether is mobile phase) obtain sample 4u, yield 51%.Dr is greater than 20:1.
Embodiment 19
In 5mL reaction flask, by silyl enol ether compound 1l (0.6mmol), perfluoro-n-hexane base iodine 2a (0.9mmol),
Alkamine compound 3k (0.3mmol), triethylene diamine (DABCO) (1.5mmol) and acriflavine (0.2mg,
It 0.0009mmol) is stirred in acetonitrile (2.0mL), through N2It replaces 3 times and is placed under 4.5 watts of white light-emitting diodes and shine
It penetrates and is stirred to react 28 hours, TLC is detected after completion of the reaction, and concentrated reaction solution is purified by silica gel column chromatography (ethyl acetate/stone
Oily ether is mobile phase) obtain sample compound 4w, yield 64%.Dr is greater than 20:1.
Embodiment 20
In 5mL reaction flask, by substituted acetophenone compound 1l ' (0.6mmol) and triisopropylsilyl trifluoromethanesulfonic acid
After reaction 2h is stirred at room temperature in ester (TIPSOTf, 0.9mmol) and triethylamine (0.9mmol), perfluoro-n-hexane base iodine 2a is added
(0.9mmol), alkamine compound 3a (0.3mmol), triethylene diamine (DABCO) (1.5mmol), acriflavine (0.2mg,
0.0009mmol) and acetonitrile (2.0mL), through N2Displacement, which is placed on to irradiate under 4.5 watts of white light-emitting diodes for 3 times, to be stirred to react
35 hours, TLC detect after completion of the reaction, concentrated reaction solution, be purified by silica gel column chromatography (ethyl acetate/petroleum ether for flowing
Phase) obtain sample compound 4l, yield 56%.Dr is greater than 20:1.
Embodiment 21
In 5mL reaction flask, by substituted acetophenone compound 1k ' (0.6mmol) and triisopropylsilyl trifluoromethanesulfonic acid
After reaction 2h is stirred at room temperature in ester (TIPSOTf, 0.9mmol) and triethylamine (0.9mmol), perfluoro-n-hexane base iodine 2a is added
(0.9mmol), alkamine compound 3a (0.3mmol), triethylene diamine (DABCO) (1.5mmol), acriflavine (0.2mg,
0.0009mmol) and acetonitrile (2.0mL), through N2Displacement, which is placed on to irradiate under 4.5 watts of white light-emitting diodes for 3 times, to be stirred to react
35 hours, TLC detect after completion of the reaction, concentrated reaction solution, be purified by silica gel column chromatography (ethyl acetate/petroleum ether for flowing
Phase) obtain sample compound 4l, yield 56%.Dr is greater than 20:1.
Claims (10)
1. a kind of preparation method of compound shown in formula 4,
Including, under the conditions of photochemical catalyst, the step of 1 compound of formula, 2 compound of formula and 3 compound of formula reaction 4 compound of acquisition formula
Suddenly,
Wherein, R1、R2Selected from hydrogen, alkyl, alkenyl, alkynyl, naphthenic base, heterocycle, aryl and heteroaryl, wherein the alkyl,
Alkenyl, alkynyl, naphthenic base, heterocycle, aryl and heteroaryl optionally by selected from alkyl, halogen, hydroxyl, amino, oxygroup, carboxyl,
Replaced one or more substituent groups in nitro, cyano, alkoxy, naphthenic base, heterocycle, aryl and heteroaryl, alternatively,
R1、R2Carbon atom adjacent thereto is formed together 5 yuan to 10 yuan carbocyclic rings, heterocycle or condensed ring, preferably 6 yuan to 8 yuan carbocyclic rings, heterocycle or thick
Ring, the carbocyclic ring, heterocycle or condensed ring are optionally selected from alkyl, halogen, hydroxyl, amino, oxygroup, carboxyl, nitro, cyano, alcoxyl
Replaced one or more substituent groups in base, naphthenic base, heterocycle, aryl and heteroaryl；
R3、R4、R5, R6Selected from hydrogen, alkyl, alkenyl, alkynyl, naphthenic base, heterocycle, aryl and heteroaryl, wherein the alkyl,
Alkenyl, alkynyl, naphthenic base, heterocycle, aryl and heteroaryl optionally by selected from alkyl, halogen, hydroxyl, amino, oxygroup, carboxyl,
Replaced one or more substituent groups in nitro, cyano, alkoxy, naphthenic base, heterocycle, aryl and heteroaryl,
Alternatively,
R5And R6Carbon atom adjacent thereto is formed together 5 yuan to 10 yuan carbocyclic rings, heterocycle or condensed ring, preferably 6 yuan to 8 yuan carbocyclic rings, heterocycles
Or condensed ring, the carbocyclic ring, heterocycle or condensed ring optionally by selected from alkyl, halogen, hydroxyl, amino, oxygroup, carboxyl, nitro, cyano,
Replaced one or more substituent groups in alkoxy, naphthenic base, heterocycle, aryl and heteroaryl；
Alternatively,
R3And R6Carbon atom adjacent thereto is formed together 5 yuan to 10 yuan carbocyclic rings, heterocycle or condensed ring, preferably 6 yuan to 8 yuan carbocyclic rings, heterocycles
Or condensed ring, the carbocyclic ring, heterocycle or condensed ring optionally by selected from alkyl, halogen, hydroxyl, amino, oxygroup, carboxyl, nitro, cyano,
Replaced one or more substituent groups in alkoxy, naphthenic base, heterocycle, aryl and heteroaryl；
P is selected from trimethyl silicon substrate, triisopropylsilyl or dimethyl tertiary butyl silicon substrate, preferably triisopropylsilyl；
N is the integer between 2~10.
2. the preferably described light urges the use of agent according to the method described in claim 1, wherein the photochemical catalyst is selected from acriflavine
Amount is the 0.1~1% of 1 compound mole of formula.
3. method according to claim 1 or 2, wherein the R1Selected from phenyl, naphthalene and pyridyl group, the phenyl, naphthalene
Optionally C is selected from pyridyl group1-6Alkyl, halogen, hydroxyl, amino, carboxyl, nitro, cyano, C1-6Alkoxy, C3-8Naphthenic base,
C3-8Replaced one or more substituent groups in heterocycle, aryl and heteroaryl.
4. method according to claim 1-3, wherein 3 compound of formula is selected from:
5. method according to claim 1-4, wherein 4 compound of formula is selected from:
6. method according to claim 1-5, wherein including alkali in the reaction, the alkali is selected from triethylene two
Amine, diisopropylamine, preferably triethylene diamine.
7. method according to claim 1-6, wherein the reaction solvent for use is selected from acetonitrile, N, N- dimethyl
Formamide, acetone and tetrahydrofuran, preferably acetonitrile.
8. method according to claim 1-7, wherein illumination light source used in the reaction is 4.5 watts of white hairs
Optical diode.
9. method according to claim 1-8, wherein the reaction temperature is selected from 10~50 DEG C, preferably 15~30
℃。
10. a kind of method for preparing drug, fragrance or pesticide, including chemical combination shown in formula described in any one of claim 1-9 4
The preparation method of object.
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Patent Citations (1)
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| CN107365278A (en) * | 2017-06-09 | 2017-11-21 | 衢州英特高分子材料有限公司 | A kind of polysubstituted isoxazole alkane derivatives and preparation method thereof |
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| JOHNATHAN V. MATLOCK 等: "Synthesis of 6- and 7‑Membered N‑Heterocycles Using α‑Phenylvinylsulfonium Salts", 《ORG. LETT.》 * |
| KEVIN R. CAMPOS: "Direct sp3 C–H bond activation adjacent to nitrogen in heterocycles", 《CHEM. SOC. REV.》 * |
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