SK42897A3 - Process for producing enantiomerically clean cycloalkano indol- and azaindol-, and pyrimido£1,2-a|indolcarboxylic acids, and their activated derivatives, intermediate products for this process and their use - Google Patents

Process for producing enantiomerically clean cycloalkano indol- and azaindol-, and pyrimido£1,2-a|indolcarboxylic acids, and their activated derivatives, intermediate products for this process and their use Download PDF

Info

Publication number: SK42897A3
Authority: SK; Slovakia
Prior art keywords: formula; group; carbon atoms; straight; compounds
Prior art date: 1996-04-04

Application number

SK428-97A

Other languages

English (en)

Slovak (sk)

Inventor

Jan-Bernd Lenfers

Peter Fey

Paul Naab

Laak Kai Van

Original Assignee

Bayer Ag

Priority date (The priority date 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 date listed.)

1996-04-04

Filing date

1997-04-03

Publication date

1997-10-08

1997-04-03 Application filed by Bayer Ag filed Critical Bayer Ag

1997-10-08 Publication of SK42897A3 publication Critical patent/SK42897A3/sk

Links

238000000034 method Methods 0.000 title claims abstract description 30
239000002253 acid Substances 0.000 title claims abstract description 12
150000007513 acids Chemical class 0.000 title claims description 10
239000013067 intermediate product Substances 0.000 title 1
150000001875 compounds Chemical class 0.000 claims abstract description 81
238000006243 chemical reaction Methods 0.000 claims abstract description 28
125000000217 alkyl group Chemical group 0.000 claims abstract description 27
125000003545 alkoxy group Chemical group 0.000 claims abstract description 22
229910052794 bromium Inorganic materials 0.000 claims abstract description 19
229910052801 chlorine Inorganic materials 0.000 claims abstract description 18
150000003839 salts Chemical class 0.000 claims abstract description 14
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 12
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 12
238000002425 crystallisation Methods 0.000 claims abstract description 11
VQTUBCCKSQIDNK-UHFFFAOYSA-N Isobutene Chemical compound CC(C)=C VQTUBCCKSQIDNK-UHFFFAOYSA-N 0.000 claims abstract description 10
230000026030 halogenation Effects 0.000 claims abstract description 10
238000005658 halogenation reaction Methods 0.000 claims abstract description 10
239000012442 inert solvent Substances 0.000 claims abstract description 9
229910052740 iodine Inorganic materials 0.000 claims abstract description 9
BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical class NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 claims abstract description 8
230000007062 hydrolysis Effects 0.000 claims abstract description 8
238000006460 hydrolysis reaction Methods 0.000 claims abstract description 8
238000002360 preparation method Methods 0.000 claims abstract description 8
125000003158 alcohol group Chemical group 0.000 claims abstract description 4
150000001925 cycloalkenes Chemical class 0.000 claims abstract description 4
238000011873 diastereoselective alkylation Methods 0.000 claims abstract description 4
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 3
125000004170 methylsulfonyl group Chemical group [H]C([H])([H])S(*)(=O)=O 0.000 claims abstract description 3
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 3
125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 claims abstract description 3
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims abstract 2
125000004432 carbon atom Chemical group C* 0.000 claims description 51
-1 azaindole carboxylic acids Chemical class 0.000 claims description 31
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 19
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 18
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 17
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
239000000460 chlorine Substances 0.000 claims description 15
150000002148 esters Chemical class 0.000 claims description 15
230000003213 activating effect Effects 0.000 claims description 13
150000003254 radicals Chemical class 0.000 claims description 12
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 11
125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 11
230000008025 crystallization Effects 0.000 claims description 10
HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 claims description 8
LPIQUOYDBNQMRZ-UHFFFAOYSA-N cyclopentene Chemical compound C1CC=CC1 LPIQUOYDBNQMRZ-UHFFFAOYSA-N 0.000 claims description 8
239000000543 intermediate Substances 0.000 claims description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 8
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 7
229910052736 halogen Inorganic materials 0.000 claims description 7
150000002367 halogens Chemical class 0.000 claims description 7
229910052739 hydrogen Inorganic materials 0.000 claims description 7
125000004076 pyridyl group Chemical group 0.000 claims description 7
125000000753 cycloalkyl group Chemical group 0.000 claims description 6
239000001257 hydrogen Substances 0.000 claims description 6
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims description 6
229960003424 phenylacetic acid Drugs 0.000 claims description 6
239000003279 phenylacetic acid Substances 0.000 claims description 6
CRIQVNJLXZMCJM-UHFFFAOYSA-N N1=C(C=CN2C3=CC=CC=C3C=C12)C(=O)O Chemical class N1=C(C=CN2C3=CC=CC=C3C=C12)C(=O)O CRIQVNJLXZMCJM-UHFFFAOYSA-N 0.000 claims description 5
229910052731 fluorine Inorganic materials 0.000 claims description 5
239000011737 fluorine Substances 0.000 claims description 5
150000001735 carboxylic acids Chemical class 0.000 claims description 4
ZXIJMRYMVAMXQP-UHFFFAOYSA-N cycloheptene Chemical compound C1CCC=CCC1 ZXIJMRYMVAMXQP-UHFFFAOYSA-N 0.000 claims description 4
URYYVOIYTNXXBN-UPHRSURJSA-N cyclooctene Chemical compound C1CCC\C=C/CC1 URYYVOIYTNXXBN-UPHRSURJSA-N 0.000 claims description 4
239000004913 cyclooctene Substances 0.000 claims description 4
RGSFGYAAUTVSQA-UHFFFAOYSA-N pentamethylene Natural products C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 claims description 4
LBJYCOSMENQQQK-ZDUSSCGKSA-N (2s)-2-cyclopentyl-2-(4-methylphenyl)acetic acid Chemical compound C1=CC(C)=CC=C1[C@@H](C(O)=O)C1CCCC1 LBJYCOSMENQQQK-ZDUSSCGKSA-N 0.000 claims description 3
239000003153 chemical reaction reagent Substances 0.000 claims description 3
125000001309 chloro group Chemical group Cl* 0.000 claims description 3
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 claims 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 claims description 3
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 claims description 3
125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
125000004213 tert-butoxy group Chemical group [H]C([H])([H])C(O*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 3
NGNBDVOYPDDBFK-UHFFFAOYSA-N 2-[2,4-di(pentan-2-yl)phenoxy]acetyl chloride Chemical compound CCCC(C)C1=CC=C(OCC(Cl)=O)C(C(C)CCC)=C1 NGNBDVOYPDDBFK-UHFFFAOYSA-N 0.000 claims description 2
VMZCDNSFRSVYKQ-UHFFFAOYSA-N 2-phenylacetyl chloride Chemical compound ClC(=O)CC1=CC=CC=C1 VMZCDNSFRSVYKQ-UHFFFAOYSA-N 0.000 claims description 2
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 2
KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 2
125000004122 cyclic group Chemical group 0.000 claims description 2
125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 2
125000005843 halogen group Chemical group 0.000 claims description 2
239000011630 iodine Substances 0.000 claims description 2
125000004430 oxygen atom Chemical group O* 0.000 claims description 2
VQOWAMGSDNVFCV-INIZCTEOSA-N tert-butyl (2s)-2-[4-(bromomethyl)phenyl]-2-cyclopentylacetate Chemical compound C1([C@H](C(=O)OC(C)(C)C)C=2C=CC(CBr)=CC=2)CCCC1 VQOWAMGSDNVFCV-INIZCTEOSA-N 0.000 claims description 2
IJXJGQCXFSSHNL-UHFFFAOYSA-N 2-amino-2-phenylethanol Chemical group OCC(N)C1=CC=CC=C1 IJXJGQCXFSSHNL-UHFFFAOYSA-N 0.000 claims 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims 1
125000001153 fluoro group Chemical group F* 0.000 claims 1
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 abstract description 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 abstract description 9
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 abstract description 5
125000001475 halogen functional group Chemical group 0.000 abstract 2
BAXOFTOLAUCFNW-UHFFFAOYSA-N 1H-indazole Chemical compound C1=CC=C2C=NNC2=C1 BAXOFTOLAUCFNW-UHFFFAOYSA-N 0.000 abstract 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 abstract 1
WLJVXDMOQOGPHL-UHFFFAOYSA-N phenylacetic acid Chemical class OC(=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-UHFFFAOYSA-N 0.000 abstract 1
125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 abstract 1
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 54
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 41
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 33
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 28
239000000203 mixture Substances 0.000 description 25
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 23
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 22
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 22
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
239000002904 solvent Substances 0.000 description 20
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 16
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 15
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 15
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 13
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 12
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 12
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
239000011541 reaction mixture Substances 0.000 description 12
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 12
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
239000002585 base Substances 0.000 description 11
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
238000003756 stirring Methods 0.000 description 10
239000000725 suspension Substances 0.000 description 10
230000029936 alkylation Effects 0.000 description 9
238000005804 alkylation reaction Methods 0.000 description 9
238000004128 high performance liquid chromatography Methods 0.000 description 9
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
238000001816 cooling Methods 0.000 description 8
239000013078 crystal Substances 0.000 description 8
238000010992 reflux Methods 0.000 description 8
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 8
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
235000019441 ethanol Nutrition 0.000 description 7
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 7
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 6
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
229910052783 alkali metal Inorganic materials 0.000 description 6
235000019253 formic acid Nutrition 0.000 description 6
239000007789 gas Substances 0.000 description 6
239000012074 organic phase Substances 0.000 description 6
CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 6
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
239000000047 product Substances 0.000 description 6
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 5
230000004913 activation Effects 0.000 description 5
150000001412 amines Chemical class 0.000 description 5
239000012043 crude product Substances 0.000 description 5
239000003208 petroleum Substances 0.000 description 5
239000011780 sodium chloride Substances 0.000 description 5
239000007787 solid Substances 0.000 description 5
IJXJGQCXFSSHNL-QMMMGPOBSA-N (R)-(-)-2-Phenylglycinol Chemical compound OC[C@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-QMMMGPOBSA-N 0.000 description 4
238000005160 1H NMR spectroscopy Methods 0.000 description 4
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 4
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 4
YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
239000012298 atmosphere Substances 0.000 description 4
238000009835 boiling Methods 0.000 description 4
239000003795 chemical substances by application Substances 0.000 description 4
229960001701 chloroform Drugs 0.000 description 4
230000001681 protective effect Effects 0.000 description 4
239000007858 starting material Substances 0.000 description 4
OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 3
OZAIFHULBGXAKX-VAWYXSNFSA-N AIBN Substances N#CC(C)(C)\N=N\C(C)(C)C#N OZAIFHULBGXAKX-VAWYXSNFSA-N 0.000 description 3
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 3
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 3
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 3
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 3
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 3
150000001340 alkali metals Chemical class 0.000 description 3
229910052784 alkaline earth metal Inorganic materials 0.000 description 3
229910052799 carbon Inorganic materials 0.000 description 3
150000002170 ethers Chemical class 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
229940052308 general anesthetics halogenated hydrocarbons Drugs 0.000 description 3
150000008282 halocarbons Chemical class 0.000 description 3
230000014759 maintenance of location Effects 0.000 description 3
238000004519 manufacturing process Methods 0.000 description 3
239000000463 material Substances 0.000 description 3
239000012452 mother liquor Substances 0.000 description 3
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 3
239000003960 organic solvent Substances 0.000 description 3
229910000027 potassium carbonate Inorganic materials 0.000 description 3
229910052708 sodium Inorganic materials 0.000 description 3
239000011734 sodium Substances 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 3
239000008096 xylene Substances 0.000 description 3
PAMIQIKDUOTOBW-UHFFFAOYSA-N 1-methylpiperidine Chemical compound CN1CCCCC1 PAMIQIKDUOTOBW-UHFFFAOYSA-N 0.000 description 2
GXXXUZIRGXYDFP-UHFFFAOYSA-N 2-(4-methylphenyl)acetic acid Chemical compound CC1=CC=C(CC(O)=O)C=C1 GXXXUZIRGXYDFP-UHFFFAOYSA-N 0.000 description 2
YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 2
HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 2
CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 2
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
PHSPJQZRQAJPPF-UHFFFAOYSA-N N-alpha-Methylhistamine Chemical compound CNCCC1=CN=CN1 PHSPJQZRQAJPPF-UHFFFAOYSA-N 0.000 description 2
JRNVZBWKYDBUCA-UHFFFAOYSA-N N-chlorosuccinimide Chemical compound ClN1C(=O)CCC1=O JRNVZBWKYDBUCA-UHFFFAOYSA-N 0.000 description 2
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 2
150000008044 alkali metal hydroxides Chemical class 0.000 description 2
230000015572 biosynthetic process Effects 0.000 description 2
150000001732 carboxylic acid derivatives Chemical class 0.000 description 2
238000004587 chromatography analysis Methods 0.000 description 2
238000003776 cleavage reaction Methods 0.000 description 2
238000007796 conventional method Methods 0.000 description 2
VRLDVERQJMEPIF-UHFFFAOYSA-N dbdmh Chemical compound CC1(C)N(Br)C(=O)N(Br)C1=O VRLDVERQJMEPIF-UHFFFAOYSA-N 0.000 description 2
238000006345 epimerization reaction Methods 0.000 description 2
230000002140 halogenating effect Effects 0.000 description 2
125000000623 heterocyclic group Chemical group 0.000 description 2
GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 2
229940098779 methanesulfonic acid Drugs 0.000 description 2
238000006386 neutralization reaction Methods 0.000 description 2
LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 2
239000012071 phase Substances 0.000 description 2
RPDAUEIUDPHABB-UHFFFAOYSA-N potassium ethoxide Chemical compound [K+].CC[O-] RPDAUEIUDPHABB-UHFFFAOYSA-N 0.000 description 2
BDAWXSQJJCIFIK-UHFFFAOYSA-N potassium methoxide Chemical compound [K+].[O-]C BDAWXSQJJCIFIK-UHFFFAOYSA-N 0.000 description 2
239000002244 precipitate Substances 0.000 description 2
ZZYXNRREDYWPLN-UHFFFAOYSA-N pyridine-2,3-diamine Chemical compound NC1=CC=CN=C1N ZZYXNRREDYWPLN-UHFFFAOYSA-N 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
230000007017 scission Effects 0.000 description 2
229910000104 sodium hydride Inorganic materials 0.000 description 2
239000012312 sodium hydride Substances 0.000 description 2
KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 2
238000003786 synthesis reaction Methods 0.000 description 2
CIHOLLKRGTVIJN-UHFFFAOYSA-N tert‐butyl hydroperoxide Chemical compound CC(C)(C)OO CIHOLLKRGTVIJN-UHFFFAOYSA-N 0.000 description 2
238000005406 washing Methods 0.000 description 2
238000010626 work up procedure Methods 0.000 description 2
NOOLISFMXDJSKH-KXUCPTDWSA-N (-)-Menthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@H]1O NOOLISFMXDJSKH-KXUCPTDWSA-N 0.000 description 1
RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 description 1
IJXJGQCXFSSHNL-MRVPVSSYSA-N (2s)-2-amino-2-phenylethanol Chemical compound OC[C@@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-MRVPVSSYSA-N 0.000 description 1
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 1
YRIZYWQGELRKNT-UHFFFAOYSA-N 1,3,5-trichloro-1,3,5-triazinane-2,4,6-trione Chemical compound ClN1C(=O)N(Cl)C(=O)N(Cl)C1=O YRIZYWQGELRKNT-UHFFFAOYSA-N 0.000 description 1
KEQGZUUPPQEDPF-UHFFFAOYSA-N 1,3-dichloro-5,5-dimethylimidazolidine-2,4-dione Chemical compound CC1(C)N(Cl)C(=O)N(Cl)C1=O KEQGZUUPPQEDPF-UHFFFAOYSA-N 0.000 description 1
OCJBOOLMMGQPQU-UHFFFAOYSA-N 1,4-dichlorobenzene Chemical compound ClC1=CC=C(Cl)C=C1 OCJBOOLMMGQPQU-UHFFFAOYSA-N 0.000 description 1
ZQXCQTAELHSNAT-UHFFFAOYSA-N 1-chloro-3-nitro-5-(trifluoromethyl)benzene Chemical compound [O-][N+](=O)C1=CC(Cl)=CC(C(F)(F)F)=C1 ZQXCQTAELHSNAT-UHFFFAOYSA-N 0.000 description 1
LGJCFVYMIJLQJO-UHFFFAOYSA-N 1-dodecylperoxydodecane Chemical compound CCCCCCCCCCCCOOCCCCCCCCCCCC LGJCFVYMIJLQJO-UHFFFAOYSA-N 0.000 description 1
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
DKVDSNMJXDQNCD-UHFFFAOYSA-N 1h-pyrrolo[2,3-f]quinazoline Chemical compound N1=CN=CC2=C(NC=C3)C3=CC=C21 DKVDSNMJXDQNCD-UHFFFAOYSA-N 0.000 description 1
GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 1
MCSKLEQLDCJCBY-UHFFFAOYSA-N 2,4-dimethylpyrimido[1,2-a]indole Chemical compound C1=CC=C2N3C(C)=CC(C)=NC3=CC2=C1 MCSKLEQLDCJCBY-UHFFFAOYSA-N 0.000 description 1
WLJVXDMOQOGPHL-PPJXEINESA-N 2-phenylacetic acid Chemical compound O[14C](=O)CC1=CC=CC=C1 WLJVXDMOQOGPHL-PPJXEINESA-N 0.000 description 1
OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
VTYYLEPIZMXCLO-UHFFFAOYSA-L Calcium carbonate Chemical compound [Ca+2].[O-]C([O-])=O VTYYLEPIZMXCLO-UHFFFAOYSA-L 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
OWIKHYCFFJSOEH-UHFFFAOYSA-N Isocyanic acid Chemical compound N=C=O OWIKHYCFFJSOEH-UHFFFAOYSA-N 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 1
VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 description 1
UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 1
IPBVNPXQWQGGJP-UHFFFAOYSA-N acetic acid phenyl ester Natural products CC(=O)OC1=CC=CC=C1 IPBVNPXQWQGGJP-UHFFFAOYSA-N 0.000 description 1
239000013543 active substance Substances 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
229910000288 alkali metal carbonate Inorganic materials 0.000 description 1
150000008041 alkali metal carbonates Chemical class 0.000 description 1
229910000102 alkali metal hydride Inorganic materials 0.000 description 1
150000008046 alkali metal hydrides Chemical class 0.000 description 1
229910001860 alkaline earth metal hydroxide Inorganic materials 0.000 description 1
150000001342 alkaline earth metals Chemical class 0.000 description 1
150000001350 alkyl halides Chemical class 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
XLJMAIOERFSOGZ-UHFFFAOYSA-N anhydrous cyanic acid Natural products OC#N XLJMAIOERFSOGZ-UHFFFAOYSA-N 0.000 description 1
229940040526 anhydrous sodium acetate Drugs 0.000 description 1
230000000879 anti-atherosclerotic effect Effects 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
RQPZNWPYLFFXCP-UHFFFAOYSA-L barium dihydroxide Chemical compound [OH-].[OH-].[Ba+2] RQPZNWPYLFFXCP-UHFFFAOYSA-L 0.000 description 1
229910001863 barium hydroxide Inorganic materials 0.000 description 1
150000007514 bases Chemical class 0.000 description 1
235000019400 benzoyl peroxide Nutrition 0.000 description 1
BRTFVKHPEHKBQF-UHFFFAOYSA-N bromocyclopentane Chemical compound BrC1CCCC1 BRTFVKHPEHKBQF-UHFFFAOYSA-N 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
150000001721 carbon Chemical group 0.000 description 1
238000012512 characterization method Methods 0.000 description 1
VDQQXEISLMTGAB-UHFFFAOYSA-N chloramine T Chemical compound [Na+].CC1=CC=C(S(=O)(=O)[N-]Cl)C=C1 VDQQXEISLMTGAB-UHFFFAOYSA-N 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
239000000287 crude extract Substances 0.000 description 1
LSXWFXONGKSEMY-UHFFFAOYSA-N di-tert-butyl peroxide Chemical compound CC(C)(C)OOC(C)(C)C LSXWFXONGKSEMY-UHFFFAOYSA-N 0.000 description 1
239000012973 diazabicyclooctane Substances 0.000 description 1
229940117389 dichlorobenzene Drugs 0.000 description 1
CCAFPWNGIUBUSD-UHFFFAOYSA-N diethyl sulfoxide Chemical compound CCS(=O)CC CCAFPWNGIUBUSD-UHFFFAOYSA-N 0.000 description 1
239000003814 drug Substances 0.000 description 1
238000001035 drying Methods 0.000 description 1
230000000694 effects Effects 0.000 description 1
125000001301 ethoxy group Chemical group [H]C([H])([H])C([H])([H])O* 0.000 description 1
238000000605 extraction Methods 0.000 description 1
238000005562 fading Methods 0.000 description 1
239000006260 foam Substances 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
150000004678 hydrides Chemical class 0.000 description 1
229930195733 hydrocarbon Natural products 0.000 description 1
150000002430 hydrocarbons Chemical class 0.000 description 1
238000011081 inoculation Methods 0.000 description 1
150000007529 inorganic bases Chemical class 0.000 description 1
239000007788 liquid Substances 0.000 description 1
229910052744 lithium Inorganic materials 0.000 description 1
238000002844 melting Methods 0.000 description 1
230000008018 melting Effects 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
150000007522 mineralic acids Chemical class 0.000 description 1
238000002156 mixing Methods 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
150000007530 organic bases Chemical class 0.000 description 1
238000012856 packing Methods 0.000 description 1
239000002245 particle Substances 0.000 description 1
150000002978 peroxides Chemical class 0.000 description 1
229940117803 phenethylamine Drugs 0.000 description 1
229940049953 phenylacetate Drugs 0.000 description 1
NHKJPPKXDNZFBJ-UHFFFAOYSA-N phenyllithium Chemical compound [Li]C1=CC=CC=C1 NHKJPPKXDNZFBJ-UHFFFAOYSA-N 0.000 description 1
UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
239000000843 powder Substances 0.000 description 1
HBBKFNCURJQICW-UHFFFAOYSA-N pyrimido[1,2-a]indole Chemical class C1=CC=NC2=CC3=CC=CC=C3N21 HBBKFNCURJQICW-UHFFFAOYSA-N 0.000 description 1
230000006340 racemization Effects 0.000 description 1
239000013557 residual solvent Substances 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
238000005201 scrubbing Methods 0.000 description 1
ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
229960002317 succinimide Drugs 0.000 description 1
YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical compound ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 1
229950009390 symclosene Drugs 0.000 description 1
WVUNBBJLJPVTBU-INIZCTEOSA-N tert-butyl (2s)-2-cyclopentyl-2-(4-methylphenyl)acetate Chemical compound C1=CC(C)=CC=C1[C@@H](C(=O)OC(C)(C)C)C1CCCC1 WVUNBBJLJPVTBU-INIZCTEOSA-N 0.000 description 1
229960001479 tosylchloramide sodium Drugs 0.000 description 1
125000005270 trialkylamine group Chemical group 0.000 description 1
GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 description 1
239000003039 volatile agent Substances 0.000 description 1

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
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/612—Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a six-membered aromatic ring in the acid moiety
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/612—Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a six-membered aromatic ring in the acid moiety
- C07C69/616—Esters of carboxylic acids having a carboxyl group bound to an acyclic carbon atom and having a six-membered aromatic ring in the acid moiety polycyclic
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/62—Halogen-containing esters
- C07C69/65—Halogen-containing esters of unsaturated acids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D487/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00
- C07D487/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, not provided for by groups C07D451/00 - C07D477/00 in which the condensed system contains two hetero rings
- C07D487/04—Ortho-condensed systems

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Indole Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

SK428-97A 1996-04-04 1997-04-03 Process for producing enantiomerically clean cycloalkano indol- and azaindol-, and pyrimido£1,2-a|indolcarboxylic acids, and their activated derivatives, intermediate products for this process and their use SK42897A3 (en)

Applications Claiming Priority (1)

Application Number	Priority Date	Filing Date	Title
DE19613549A DE19613549A1 (de)	1996-04-04	1996-04-04	Verfahren zur Herstellung von enantiomerenreinen Cycloalkano-indol- und azaindol-carbonsäuren und deren aktivierte Derivate

Publications (1)

Publication Number	Publication Date
SK42897A3 true SK42897A3 (en)	1997-10-08

Family

ID=7790501

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK428-97A SK42897A3 (en)	1996-04-04	1997-04-03	Process for producing enantiomerically clean cycloalkano indol- and azaindol-, and pyrimido£1,2-a\|indolcarboxylic acids, and their activated derivatives, intermediate products for this process and their use

Country Status (27)

Country	Link
US (1)	US5952498A (id)
EP (1)	EP0799829B1 (id)
JP (2)	JP4235268B2 (id)
KR (1)	KR970069988A (id)
CN (2)	CN1067394C (id)
AR (2)	AR006544A1 (id)
AT (1)	ATE246193T1 (id)
AU (1)	AU722592B2 (id)
BR (1)	BR9701672A (id)
CA (1)	CA2201435C (id)
CZ (1)	CZ102197A3 (id)
DE (2)	DE19613549A1 (id)
DZ (1)	DZ2202A1 (id)
EE (1)	EE9700079A (id)
ES (1)	ES2202506T3 (id)
HR (1)	HRP970178A2 (id)
HU (1)	HU218494B (id)
ID (1)	ID16794A (id)
IL (1)	IL120591A (id)
MA (1)	MA24130A1 (id)
NO (2)	NO308301B1 (id)
NZ (1)	NZ314498A (id)
PL (1)	PL319269A1 (id)
SG (1)	SG60050A1 (id)
SK (1)	SK42897A3 (id)
TN (1)	TNSN97060A1 (id)
ZA (1)	ZA972831B (id)

Families Citing this family (13)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE4435477A1 (de)	1994-10-04	1996-04-11	Bayer Ag	Cycloalkano-indol- und -azaindol-derivate
AU2001244635A1 (en) *	2000-03-30	2001-10-15	Yamanouchi Pharmaceutical Co..Ltd.	Hydrazide derivatives
WO2005051382A1 (ja) *	2003-11-28	2005-06-09	Astellas Pharma Inc.	脂質低下作用増強剤
KR101494067B1 (ko)	2004-03-05	2015-02-16	더 트러스티스 오브 더 유니버시티 오브 펜실바니아	부작용을 최소화하면서 과지질혈증 및 과콜레스테롤혈증과 연관된 질환 또는 질병의 치료 방법
AU2005230397B2 (en) *	2004-04-09	2010-04-08	Elanco Animal Health Ireland Limited	Intermittent dosing regimen for the treatment of overweight with MTP-inhibitors
AU2006304689A1 (en) *	2005-10-18	2007-04-26	Aegerion Pharmaceuticals	Compositions for lowering serum cholesterol and/or triglycerides
US20080051427A1 (en) *	2006-05-18	2008-02-28	Fritz Schuckler	Pharmaceutical Compositions and Methods of Using Same
JP2010513534A (ja) *	2006-12-21	2010-04-30	エージェリオンファーマシューティカルズ，インコーポレイテッド	Ｍｔｐインヒビターおよびコレステロール吸収インヒビターを含む組み合わせを用いて肥満症を処置する方法
WO2008124384A2 (en) *	2007-04-03	2008-10-16	Aegerion Pharmaceuticals, Inc.	Combinations of mtp inhibitors with cholesterol absorption inhibitors or interferon for treating hepatitis c
PT2968284T (pt)	2013-03-14	2021-06-28	Osteoqc Inc	Derivados alquilamina de harmina para promoção de crescimento ósseo
AU2019320773B2 (en)	2018-08-14	2024-12-05	Ossifi Therapeutics Llc	Fluoro β-carboline compounds
US10947236B2 (en)	2018-08-14	2021-03-16	Osteoqc Inc.	Pyrrolo-dipyridine compounds
CA3186856A1 (en)	2020-07-29	2022-02-03	Ruth NALLEN	Lomitapide for use in methods of treating hyperlipidemia and hypercholesterolemia in pediatric patients

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE3900261A1 (de) *	1988-05-31	1989-12-07	Bayer Ag	Substituierte 4-(chinolin-2-yl-methoxy) phenyl-essigsaeure-derivate
DE4200954A1 (de) *	1991-04-26	1992-10-29	Bayer Ag	Heterocyclisch substituierte phenylessigsaeurederivate
DE4208051A1 (de) *	1992-03-13	1993-09-16	Bayer Ag	Substituierte phenylessigsaeureamide
DE4302956A1 (de) *	1993-02-03	1994-08-04	Bayer Ag	Substituierte Imidazo(4,5-b)pyridine und Benzimidazole
DE4435477A1 (de) *	1994-10-04	1996-04-11	Bayer Ag	Cycloalkano-indol- und -azaindol-derivate

1996
- 1996-04-04 DE DE19613549A patent/DE19613549A1/de not_active Withdrawn
1997
- 1997-03-24 AT AT97104941T patent/ATE246193T1/de not_active IP Right Cessation
- 1997-03-24 ES ES97104941T patent/ES2202506T3/es not_active Expired - Lifetime
- 1997-03-24 DE DE59710487T patent/DE59710487D1/de not_active Expired - Lifetime
- 1997-03-24 EP EP97104941A patent/EP0799829B1/de not_active Expired - Lifetime
- 1997-03-27 AU AU16602/97A patent/AU722592B2/en not_active Ceased
- 1997-03-27 NZ NZ314498A patent/NZ314498A/en unknown
- 1997-03-28 HR HR19613549.4A patent/HRP970178A2/xx not_active Application Discontinuation
- 1997-03-31 US US08/829,566 patent/US5952498A/en not_active Expired - Lifetime
- 1997-03-31 ID IDP971060A patent/ID16794A/id unknown
- 1997-04-01 SG SG1997001028A patent/SG60050A1/en unknown
- 1997-04-01 CA CA002201435A patent/CA2201435C/en not_active Expired - Fee Related
- 1997-04-01 JP JP09635197A patent/JP4235268B2/ja not_active Expired - Fee Related
- 1997-04-01 MA MA24543A patent/MA24130A1/fr unknown
- 1997-04-02 TN TNTNSN97060A patent/TNSN97060A1/fr unknown
- 1997-04-02 IL IL12059197A patent/IL120591A/xx not_active IP Right Cessation
- 1997-04-02 DZ DZ970049A patent/DZ2202A1/fr active
- 1997-04-03 KR KR1019970012291A patent/KR970069988A/ko not_active Withdrawn
- 1997-04-03 HU HU9700698A patent/HU218494B/hu not_active IP Right Cessation
- 1997-04-03 NO NO971513A patent/NO308301B1/no not_active IP Right Cessation
- 1997-04-03 ZA ZA9702831A patent/ZA972831B/xx unknown
- 1997-04-03 PL PL97319269A patent/PL319269A1/xx unknown
- 1997-04-03 CZ CZ971021A patent/CZ102197A3/cs unknown
- 1997-04-03 SK SK428-97A patent/SK42897A3/sk unknown
- 1997-04-03 EE EE9700079A patent/EE9700079A/xx unknown
- 1997-04-04 BR BR9701672A patent/BR9701672A/pt active Search and Examination
- 1997-04-04 AR ARP970101366A patent/AR006544A1/es unknown
- 1997-04-04 CN CN97110276A patent/CN1067394C/zh not_active Expired - Fee Related
1998
- 1998-03-06 AR ARP980101029A patent/AR012048A2/es unknown
2000
- 2000-07-24 NO NO20003784A patent/NO20003784D0/no not_active Application Discontinuation
- 2000-10-12 CN CN00133103A patent/CN1330065A/zh active Pending
2008
- 2008-01-31 JP JP2008021569A patent/JP2008169218A/ja active Pending

Also Published As

Publication number	Publication date
AU1660297A (en)	1997-10-09
CN1067394C (zh)	2001-06-20
PL319269A1 (en)	1997-10-13
CN1330065A (zh)	2002-01-09
NO20003784L (no)	1997-10-06
DZ2202A1 (fr)	2002-12-03
HRP970178A2 (en)	1998-04-30
CN1184109A (zh)	1998-06-10
NZ314498A (en)	1999-09-29
AU722592B2 (en)	2000-08-10
CZ102197A3 (en)	1997-10-15
ATE246193T1 (de)	2003-08-15
MX9702446A (es)	1997-10-31
CA2201435C (en)	2006-12-12
US5952498A (en)	1999-09-14
NO971513L (no)	1997-10-06
JPH1045759A (ja)	1998-02-17
KR970069988A (ko)	1997-11-07
IL120591A0 (en)	1997-08-14
CA2201435A1 (en)	1997-10-04
NO20003784D0 (no)	2000-07-24
ID16794A (id)	1997-11-13
DE59710487D1 (de)	2003-09-04
HU9700698D0 (en)	1997-05-28
IL120591A (en)	2000-11-21
AR006544A1 (es)	1999-09-08
MA24130A1 (fr)	1997-10-01
TNSN97060A1 (fr)	2005-03-15
AR012048A2 (es)	2000-09-27
EP0799829B1 (de)	2003-07-30
JP2008169218A (ja)	2008-07-24
ES2202506T3 (es)	2004-04-01
HU218494B (hu)	2000-09-28
NO308301B1 (no)	2000-08-28
NO971513D0 (no)	1997-04-03
EP0799829A1 (de)	1997-10-08
HUP9700698A1 (hu)	1998-01-28
SG60050A1 (en)	1999-02-22
EE9700079A (et)	1997-10-15
DE19613549A1 (de)	1997-10-09
ZA972831B (en)	1997-10-31
BR9701672A (pt)	1998-11-03
JP4235268B2 (ja)	2009-03-11

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