JPH08501104A - ある種のピロロ[3,4−bキノリン類、ある種の1H−ピラノ[3’,4’:6,7インドリジノ[1,2−bキノリン−3,14(4H,12H)−ジオン類およびある種の8−メチル−7−(オキソプロピル)−インドリジノ[1,2−bキノリン−9(11H)−オン類の製造方法 - Google Patents
ある種のピロロ[3,4−bキノリン類、ある種の1H−ピラノ[3’,4’:6,7インドリジノ[1,2−bキノリン−3,14(4H,12H)−ジオン類およびある種の8−メチル−7−(オキソプロピル)−インドリジノ[1,2−bキノリン−9(11H)−オン類の製造方法Info
- Publication number
- JPH08501104A JPH08501104A JP6507518A JP50751893A JPH08501104A JP H08501104 A JPH08501104 A JP H08501104A JP 6507518 A JP6507518 A JP 6507518A JP 50751893 A JP50751893 A JP 50751893A JP H08501104 A JPH08501104 A JP H08501104A
- Authority
- JP
- Japan
- Prior art keywords
- quinoline
- quinolin
- compound
- group
- indolizino
- 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.)
- Pending
Links
- 238000000034 method Methods 0.000 title claims abstract description 77
- 230000008569 process Effects 0.000 title claims description 8
- 238000004519 manufacturing process Methods 0.000 title description 5
- 150000003248 quinolines Chemical class 0.000 title description 3
- 229940111121 antirheumatic drug quinolines Drugs 0.000 title 1
- VSJKWCGYPAHWDS-FQEVSTJZSA-N camptothecin Chemical compound C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-FQEVSTJZSA-N 0.000 claims abstract description 70
- 150000001875 compounds Chemical class 0.000 claims abstract description 59
- VSJKWCGYPAHWDS-UHFFFAOYSA-N dl-camptothecin Natural products C1=CC=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 VSJKWCGYPAHWDS-UHFFFAOYSA-N 0.000 claims abstract description 43
- 229940127093 camptothecin Drugs 0.000 claims abstract description 36
- KLWPJMFMVPTNCC-UHFFFAOYSA-N Camptothecin Natural products CCC1(O)C(=O)OCC2=C1C=C3C4Nc5ccccc5C=C4CN3C2=O KLWPJMFMVPTNCC-UHFFFAOYSA-N 0.000 claims abstract description 35
- 150000002596 lactones Chemical group 0.000 claims abstract description 23
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 19
- 230000002194 synthesizing effect Effects 0.000 claims abstract description 16
- 125000000524 functional group Chemical group 0.000 claims abstract description 13
- 239000002253 acid Substances 0.000 claims abstract description 11
- 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims abstract description 11
- WUCIMUWUAXJBRW-UHFFFAOYSA-N c1ncc2[nH]c3ccccc3cc12 Chemical class c1ncc2[nH]c3ccccc3cc12 WUCIMUWUAXJBRW-UHFFFAOYSA-N 0.000 claims abstract description 10
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims abstract description 10
- 238000007115 1,4-cycloaddition reaction Methods 0.000 claims abstract description 8
- 150000002148 esters Chemical group 0.000 claims abstract description 8
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims abstract description 7
- 125000004665 trialkylsilyl group Chemical group 0.000 claims abstract description 6
- 125000003277 amino group Chemical group 0.000 claims abstract description 5
- 150000004820 halides Chemical class 0.000 claims abstract description 5
- 125000002088 tosyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])S(*)(=O)=O 0.000 claims abstract description 5
- MWFNDFNHIBULHZ-UHFFFAOYSA-N oxoaluminum;hydrochloride Chemical compound Cl.[Al]=O MWFNDFNHIBULHZ-UHFFFAOYSA-N 0.000 claims abstract 6
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims abstract 5
- 229910052799 carbon Inorganic materials 0.000 claims abstract 4
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 60
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 57
- -1 methyl-7- (oxopropyl) -indolizino [1,2-b] quinolin-9 (11H) -ones Chemical class 0.000 claims description 52
- UCFGDBYHRUNTLO-QHCPKHFHSA-N topotecan Chemical compound C1=C(O)C(CN(C)C)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 UCFGDBYHRUNTLO-QHCPKHFHSA-N 0.000 claims description 28
- 229960000303 topotecan Drugs 0.000 claims description 28
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 27
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 26
- SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 20
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 20
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 20
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 239000003153 chemical reaction reagent Substances 0.000 claims description 15
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 14
- HJUGFYREWKUQJT-UHFFFAOYSA-N tetrabromomethane Chemical compound BrC(Br)(Br)Br HJUGFYREWKUQJT-UHFFFAOYSA-N 0.000 claims description 14
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 claims description 14
- KLFJSYOEEYWQMR-NRFANRHFSA-N 10-methoxycamptothecin Chemical compound C1=C(OC)C=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 KLFJSYOEEYWQMR-NRFANRHFSA-N 0.000 claims description 13
- WAZSVCKLDOMJJX-UHFFFAOYSA-N 2h-pyrrolo[3,4-b]quinoline Chemical class C1=CC=CC2=CC3=CNC=C3N=C21 WAZSVCKLDOMJJX-UHFFFAOYSA-N 0.000 claims description 13
- SNNLGDCYCOKWFN-UHFFFAOYSA-N C1=CC=C2C=C(CN3C4=CC=5CC(OCC=5C3=O)=O)C4=NC2=C1 Chemical class C1=CC=C2C=C(CN3C4=CC=5CC(OCC=5C3=O)=O)C4=NC2=C1 SNNLGDCYCOKWFN-UHFFFAOYSA-N 0.000 claims description 13
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 claims description 13
- 239000002798 polar solvent Substances 0.000 claims description 12
- WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 claims description 12
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 12
- 239000002168 alkylating agent Substances 0.000 claims description 11
- 229940100198 alkylating agent Drugs 0.000 claims description 11
- 150000001412 amines Chemical class 0.000 claims description 11
- 150000002576 ketones Chemical class 0.000 claims description 11
- HAWSQZCWOQZXHI-FQEVSTJZSA-N 10-Hydroxycamptothecin Chemical compound C1=C(O)C=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)[C@]5(O)CC)C4=NC2=C1 HAWSQZCWOQZXHI-FQEVSTJZSA-N 0.000 claims description 10
- 125000000217 alkyl group Chemical group 0.000 claims description 10
- 238000006243 chemical reaction Methods 0.000 claims description 10
- 230000008878 coupling Effects 0.000 claims description 10
- 238000010168 coupling process Methods 0.000 claims description 10
- 238000005859 coupling reaction Methods 0.000 claims description 10
- UWKQSNNFCGGAFS-XIFFEERXSA-N irinotecan Chemical compound C1=C2C(CC)=C3CN(C(C4=C([C@@](C(=O)OC4)(O)CC)C=4)=O)C=4C3=NC2=CC=C1OC(=O)N(CC1)CCC1N1CCCCC1 UWKQSNNFCGGAFS-XIFFEERXSA-N 0.000 claims description 10
- 238000010189 synthetic method Methods 0.000 claims description 10
- OFOBLEOULBTSOW-UHFFFAOYSA-L Malonate Chemical compound [O-]C(=O)CC([O-])=O OFOBLEOULBTSOW-UHFFFAOYSA-L 0.000 claims description 9
- 238000007363 ring formation reaction Methods 0.000 claims description 9
- HAWSQZCWOQZXHI-UHFFFAOYSA-N CPT-OH Natural products C1=C(O)C=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 HAWSQZCWOQZXHI-UHFFFAOYSA-N 0.000 claims description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 8
- 150000005690 diesters Chemical class 0.000 claims description 8
- 150000002085 enols Chemical class 0.000 claims description 8
- 229960004768 irinotecan Drugs 0.000 claims description 8
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 7
- 150000003949 imides Chemical class 0.000 claims description 7
- LVWZTYCIRDMTEY-UHFFFAOYSA-N metamizole Chemical class O=C1C(N(CS(O)(=O)=O)C)=C(C)N(C)N1C1=CC=CC=C1 LVWZTYCIRDMTEY-UHFFFAOYSA-N 0.000 claims description 7
- 238000010992 reflux Methods 0.000 claims description 7
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 7
- XVMZDZFTCKLZTF-UHFFFAOYSA-N 9-methoxycamtothecin Natural products C1=CC(OC)=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 XVMZDZFTCKLZTF-UHFFFAOYSA-N 0.000 claims description 6
- KLFJSYOEEYWQMR-UHFFFAOYSA-N CPT-OMe Natural products C1=C(OC)C=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5(O)CC)C4=NC2=C1 KLFJSYOEEYWQMR-UHFFFAOYSA-N 0.000 claims description 6
- VDDXQSUSMHZCLS-UHFFFAOYSA-N ethenyl trifluoromethanesulfonate Chemical compound FC(F)(F)S(=O)(=O)OC=C VDDXQSUSMHZCLS-UHFFFAOYSA-N 0.000 claims description 6
- RUSBSDNMQPMWPD-UHFFFAOYSA-N 7-hydroxy-6,11-dihydro-5h-indolizino[1,2-b]quinolin-9-one Chemical compound C1C2=CC3=CC=CC=C3NC2=C2N1C(=O)C=C(O)C2 RUSBSDNMQPMWPD-UHFFFAOYSA-N 0.000 claims description 5
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 claims description 5
- 150000001408 amides Chemical class 0.000 claims description 5
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 5
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 claims description 5
- 238000010438 heat treatment Methods 0.000 claims description 5
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 5
- 150000002465 imidoyl halides Chemical class 0.000 claims description 5
- 125000003158 alcohol group Chemical group 0.000 claims description 4
- HUZCTWYDQIQZPM-UHFFFAOYSA-N benzyl 2,2,2-trichloroethanimidate Chemical compound ClC(Cl)(Cl)C(=N)OCC1=CC=CC=C1 HUZCTWYDQIQZPM-UHFFFAOYSA-N 0.000 claims description 4
- 238000006210 cyclodehydration reaction Methods 0.000 claims description 4
- 238000003379 elimination reaction Methods 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- VGIVLIHKENZQHQ-UHFFFAOYSA-N n,n,n',n'-tetramethylmethanediamine Chemical compound CN(C)CN(C)C VGIVLIHKENZQHQ-UHFFFAOYSA-N 0.000 claims description 4
- 229920006395 saturated elastomer Polymers 0.000 claims description 4
- KXDHJXZQYSOELW-UHFFFAOYSA-N Carbamic acid Chemical group NC(O)=O KXDHJXZQYSOELW-UHFFFAOYSA-N 0.000 claims description 3
- 238000006228 Dieckmann condensation reaction Methods 0.000 claims description 3
- LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 claims description 3
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 3
- 229910002092 carbon dioxide Inorganic materials 0.000 claims description 3
- 238000006114 decarboxylation reaction Methods 0.000 claims description 3
- 150000004703 alkoxides Chemical class 0.000 claims description 2
- 239000001569 carbon dioxide Substances 0.000 claims description 2
- 238000009833 condensation Methods 0.000 claims description 2
- 230000005494 condensation Effects 0.000 claims description 2
- 238000006352 cycloaddition reaction Methods 0.000 claims description 2
- 230000008030 elimination Effects 0.000 claims description 2
- 230000002829 reductive effect Effects 0.000 claims description 2
- 230000018044 dehydration Effects 0.000 claims 4
- 238000006297 dehydration reaction Methods 0.000 claims 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims 2
- FBGCJOHMGWZUII-UHFFFAOYSA-N 19-ethyl-7-methoxy-17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1(21),2(11),3,5,7,9,15(20)-heptaene-14,18-dione Chemical compound C1=C(OC)C=C2C=C(CN3C4=CC5=C(C3=O)COC(=O)C5CC)C4=NC2=C1 FBGCJOHMGWZUII-UHFFFAOYSA-N 0.000 claims 1
- OZIVLIFPJDZGOQ-UHFFFAOYSA-N 6,11-dihydro-5h-indolizino[1,2-b]quinolin-9-one Chemical group N1C2=CC=CC=C2C=C2C1=C1CC=CC(=O)N1C2 OZIVLIFPJDZGOQ-UHFFFAOYSA-N 0.000 claims 1
- QAOWNCQODCNURD-UHFFFAOYSA-L Sulfate Chemical compound [O-]S([O-])(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-L 0.000 claims 1
- 125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 claims 1
- 150000002168 ethanoic acid esters Chemical class 0.000 claims 1
- 230000026030 halogenation Effects 0.000 claims 1
- 238000005658 halogenation reaction Methods 0.000 claims 1
- OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 claims 1
- 150000007513 acids Chemical class 0.000 abstract description 3
- ZNULRXDDSBVRSO-UHFFFAOYSA-N 17-oxa-3,13-diazapentacyclo[11.8.0.02,11.04,9.015,20]henicosa-1,3,5,7,9,11,14,18,20-nonaene Chemical class C1=CC=CC2=CC3=CN(C=C4COC=CC4=C4)C4=C3N=C21 ZNULRXDDSBVRSO-UHFFFAOYSA-N 0.000 abstract 1
- 230000004913 activation Effects 0.000 abstract 1
- UBQKCCHYAOITMY-UHFFFAOYSA-N pyridin-2-ol Chemical group OC1=CC=CC=N1 UBQKCCHYAOITMY-UHFFFAOYSA-N 0.000 abstract 1
- 125000003118 aryl group Chemical group 0.000 description 59
- 239000000203 mixture Substances 0.000 description 28
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 23
- 239000000243 solution Substances 0.000 description 22
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 17
- 239000000047 product Substances 0.000 description 17
- 239000007787 solid Substances 0.000 description 17
- 239000007858 starting material Substances 0.000 description 17
- 238000005160 1H NMR spectroscopy Methods 0.000 description 15
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 15
- 239000012044 organic layer Substances 0.000 description 14
- 238000003786 synthesis reaction Methods 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 230000015572 biosynthetic process Effects 0.000 description 12
- 238000002844 melting Methods 0.000 description 11
- 230000008018 melting Effects 0.000 description 11
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 10
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 8
- 235000019439 ethyl acetate Nutrition 0.000 description 8
- 239000010410 layer Substances 0.000 description 8
- 108020004414 DNA Proteins 0.000 description 7
- YJSPDKPPDSKBQZ-UHFFFAOYSA-N 11h-indolizino[1,2-b]quinolin-9-one Chemical class C1=CC=C2C=C(CN3C(=O)C=CC=C33)C3=NC2=C1 YJSPDKPPDSKBQZ-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- NEHMKBQYUWJMIP-UHFFFAOYSA-N chloromethane Chemical compound ClC NEHMKBQYUWJMIP-UHFFFAOYSA-N 0.000 description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 238000006257 total synthesis reaction Methods 0.000 description 6
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 238000003776 cleavage reaction Methods 0.000 description 5
- 238000001914 filtration Methods 0.000 description 5
- 125000004005 formimidoyl group Chemical group [H]\N=C(/[H])* 0.000 description 5
- 229910000042 hydrogen bromide Inorganic materials 0.000 description 5
- 239000000543 intermediate Substances 0.000 description 5
- 230000007017 scission Effects 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 239000000126 substance Substances 0.000 description 5
- 102000003915 DNA Topoisomerases Human genes 0.000 description 4
- 108090000323 DNA Topoisomerases Proteins 0.000 description 4
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 4
- 206010028980 Neoplasm Diseases 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
- 102000007537 Type II DNA Topoisomerases Human genes 0.000 description 4
- 108010046308 Type II DNA Topoisomerases Proteins 0.000 description 4
- 150000001450 anions Chemical class 0.000 description 4
- 238000013459 approach Methods 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 4
- 235000019341 magnesium sulphate Nutrition 0.000 description 4
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 238000001953 recrystallisation Methods 0.000 description 4
- 230000010076 replication Effects 0.000 description 4
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 4
- 238000003756 stirring Methods 0.000 description 4
- 125000001424 substituent group Chemical group 0.000 description 4
- 238000001308 synthesis method Methods 0.000 description 4
- BCMGEDGPGRHWES-UHFFFAOYSA-N 3-(8-methyl-9-oxo-11h-indolizino[1,2-b]quinolin-7-yl)propanal Chemical class C1=CC=C2C=C(CN3C4=CC(CCC=O)=C(C3=O)C)C4=NC2=C1 BCMGEDGPGRHWES-UHFFFAOYSA-N 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- 230000003213 activating effect Effects 0.000 description 3
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 3
- 239000013078 crystal Substances 0.000 description 3
- 239000005457 ice water Substances 0.000 description 3
- 150000002463 imidates Chemical class 0.000 description 3
- 229940050176 methyl chloride Drugs 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Chemical compound [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- 238000013518 transcription Methods 0.000 description 3
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- CMWTZPSULFXXJA-VIFPVBQESA-N naproxen Chemical group C1=C([C@H](C)C(O)=O)C=CC2=CC(OC)=CC=C21 CMWTZPSULFXXJA-VIFPVBQESA-N 0.000 description 1
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- XLYOFNOQVPJJNP-UHFFFAOYSA-O oxonium Chemical compound [OH3+] XLYOFNOQVPJJNP-UHFFFAOYSA-O 0.000 description 1
- BHAAPTBBJKJZER-UHFFFAOYSA-N p-anisidine Chemical compound COC1=CC=C(N)C=C1 BHAAPTBBJKJZER-UHFFFAOYSA-N 0.000 description 1
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- LISFMEBWQUVKPJ-UHFFFAOYSA-N quinolin-2-ol Chemical compound C1=CC=C2NC(=O)C=CC2=C1 LISFMEBWQUVKPJ-UHFFFAOYSA-N 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/12—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains three hetero rings
- C07D471/14—Ortho-condensed systems
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
- C07D493/12—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains three hetero rings
- C07D493/14—Ortho-condensed systems
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US94149692A | 1992-09-08 | 1992-09-08 | |
US07/941,496 | 1992-09-08 | ||
PCT/US1993/008434 WO1994005672A1 (en) | 1992-09-08 | 1993-09-08 | PROCESS FOR PREPARING CERTAIN PYRROLO[3,4- b]QUINOLINES, CERTAIN 1H-PYRANO[3',4':6,7]INDOLIZINO[1,2-b]QUINOLIN-3,14(4H,12H)-DIONES, AND CERTAIN 8-METHYL-7-(OXOPROPYL)-INDOLIZINO[1,2-b]QUINOLIN-9(11H)-ONES |
Publications (1)
Publication Number | Publication Date |
---|---|
JPH08501104A true JPH08501104A (ja) | 1996-02-06 |
Family
ID=25476581
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP6507518A Pending JPH08501104A (ja) | 1992-09-08 | 1993-09-08 | ある種のピロロ[3,4−bキノリン類、ある種の1H−ピラノ[3’,4’:6,7インドリジノ[1,2−bキノリン−3,14(4H,12H)−ジオン類およびある種の8−メチル−7−(オキソプロピル)−インドリジノ[1,2−bキノリン−9(11H)−オン類の製造方法 |
Country Status (11)
Country | Link |
---|---|
EP (1) | EP0660835A4 (zh) |
JP (1) | JPH08501104A (zh) |
KR (1) | KR950702987A (zh) |
CN (1) | CN1096297A (zh) |
AU (2) | AU5102393A (zh) |
CA (1) | CA2144048A1 (zh) |
MX (1) | MX9305517A (zh) |
NZ (1) | NZ255942A (zh) |
TW (1) | TW246674B (zh) |
WO (1) | WO1994005672A1 (zh) |
ZA (1) | ZA936580B (zh) |
Families Citing this family (4)
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US6660861B1 (en) * | 2003-03-27 | 2003-12-09 | Council Of Scientific And Industrial Research | Process for preparing Topotecan from 10-hydroxy-4-(S) camptothecin |
CN2757510Y (zh) | 2004-12-06 | 2006-02-08 | 鸿富锦精密工业(深圳)有限公司 | 散热器扣具 |
US7520313B2 (en) | 2006-03-16 | 2009-04-21 | Fu Zhun Precision Industry (Shen Zhen) Co., Ltd. | Locking device for heat sink |
CN105859716B (zh) * | 2016-05-06 | 2018-03-09 | 华东师范大学 | 一种合成喜树碱类化合物中5‑6并环结构的方法 |
Family Cites Families (6)
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JPS5626677B2 (zh) * | 1973-03-26 | 1981-06-19 | ||
JPS5217499A (en) * | 1975-07-31 | 1977-02-09 | Nippon Chemiphar Co Ltd | Preparation of mappicine |
DE2534601C2 (de) * | 1975-08-02 | 1987-01-22 | Basf Ag, 6700 Ludwigshafen | Verfahren zur Herstellung von Camptothecin und Camptothecin-Derivaten |
CA1332413C (en) * | 1987-06-25 | 1994-10-11 | Kabushiki Kaisha Yakult Honsha | Camptothecin derivatives and process for preparing same |
JP2711728B2 (ja) * | 1989-08-29 | 1998-02-10 | 株式会社ヤクルト本社 | 新規キノリン誘導体およびその製造法 |
US5155225A (en) * | 1990-09-28 | 1992-10-13 | Smithkline Beecham Corporation | Method for making certain pyrano[3',4':6,7]indolizino-[1,2-B]quinolinones |
-
1993
- 1993-09-07 ZA ZA936580A patent/ZA936580B/xx unknown
- 1993-09-08 MX MX9305517A patent/MX9305517A/es unknown
- 1993-09-08 CA CA002144048A patent/CA2144048A1/en not_active Abandoned
- 1993-09-08 WO PCT/US1993/008434 patent/WO1994005672A1/en not_active Application Discontinuation
- 1993-09-08 JP JP6507518A patent/JPH08501104A/ja active Pending
- 1993-09-08 AU AU51023/93A patent/AU5102393A/en not_active Abandoned
- 1993-09-08 EP EP93920496A patent/EP0660835A4/en not_active Withdrawn
- 1993-09-08 KR KR1019950700883A patent/KR950702987A/ko not_active Withdrawn
- 1993-09-08 NZ NZ255942A patent/NZ255942A/en unknown
- 1993-09-08 CN CN93119287A patent/CN1096297A/zh active Pending
- 1993-11-02 TW TW082109133A patent/TW246674B/zh active
-
1997
- 1997-07-11 AU AU28591/97A patent/AU2859197A/en not_active Abandoned
Also Published As
Publication number | Publication date |
---|---|
WO1994005672A1 (en) | 1994-03-17 |
TW246674B (zh) | 1995-05-01 |
CN1096297A (zh) | 1994-12-14 |
NZ255942A (en) | 1996-11-26 |
EP0660835A4 (en) | 1995-08-16 |
CA2144048A1 (en) | 1994-03-17 |
ZA936580B (en) | 1994-08-01 |
AU5102393A (en) | 1994-03-29 |
EP0660835A1 (en) | 1995-07-05 |
AU2859197A (en) | 1997-10-23 |
KR950702987A (ko) | 1995-08-23 |
MX9305517A (es) | 1994-05-31 |
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