NO323828B1 - Fremgangsmate og mellomprodukter for fremstilling av 1-(9H-karbazol-4-yloksy)-3-[2-(2-metoksyfenoksy)-etylamino]-propan-2-ol, karvedilol eller syreaddisjonssalter derav - Google Patents

Fremgangsmate og mellomprodukter for fremstilling av 1-(9H-karbazol-4-yloksy)-3-[2-(2-metoksyfenoksy)-etylamino]-propan-2-ol, karvedilol eller syreaddisjonssalter derav Download PDF

Info

Publication number: NO323828B1
Authority: NO; Norway
Prior art keywords: compound; acid; general formula; chlorine; methoxyphenoxy
Prior art date: 2000-05-18

Application number

NO20025476A

Other languages

English (en)

Norwegian (no)

Other versions

NO20025476L (no

NO20025476D0 (no

Inventor

Erik Fischer

Svend Peter Treppendahl

Thomas Pittelkow

Original Assignee

Hexal As

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.)

2000-05-18

Filing date

2002-11-15

Publication date

2007-07-09

2002-11-15 Application filed by Hexal As filed Critical Hexal As

2002-11-15 Publication of NO20025476L publication Critical patent/NO20025476L/no

2002-11-15 Publication of NO20025476D0 publication Critical patent/NO20025476D0/no

2007-07-09 Publication of NO323828B1 publication Critical patent/NO323828B1/no

Links

238000000034 method Methods 0.000 title claims description 34
OGHNVEJMJSYVRP-UHFFFAOYSA-N carvedilol Chemical compound COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=C1C1=CC=CC=C1N2 OGHNVEJMJSYVRP-UHFFFAOYSA-N 0.000 title claims description 32
239000002253 acid Substances 0.000 title claims description 27
150000003839 salts Chemical class 0.000 title claims description 26
229960004195 carvedilol Drugs 0.000 title abstract description 30
238000002360 preparation method Methods 0.000 title abstract description 11
239000000543 intermediate Substances 0.000 title description 6
150000001875 compounds Chemical class 0.000 claims description 74
238000006243 chemical reaction Methods 0.000 claims description 42
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 22
239000000460 chlorine Substances 0.000 claims description 22
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 20
229910052801 chlorine Inorganic materials 0.000 claims description 20
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 17
UEOHATPGKDSULR-UHFFFAOYSA-N 9h-carbazol-4-ol Chemical compound N1C2=CC=CC=C2C2=C1C=CC=C2O UEOHATPGKDSULR-UHFFFAOYSA-N 0.000 claims description 15
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 15
PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 15
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 15
229910052794 bromium Inorganic materials 0.000 claims description 15
239000011737 fluorine Substances 0.000 claims description 15
229910052731 fluorine Inorganic materials 0.000 claims description 15
239000002904 solvent Substances 0.000 claims description 15
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 11
125000005492 nosylate group Chemical group 0.000 claims description 11
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 11
150000008648 triflates Chemical class 0.000 claims description 11
WBCHXQLSBZVRIS-UHFFFAOYSA-N 5-(9h-carbazol-4-yloxymethyl)-3-[2-(2-methoxyphenoxy)ethyl]-1,3-oxazolidin-2-one Chemical compound COC1=CC=CC=C1OCCN1C(=O)OC(COC=2C=3C4=CC=CC=C4NC=3C=CC=2)C1 WBCHXQLSBZVRIS-UHFFFAOYSA-N 0.000 claims description 8
230000007062 hydrolysis Effects 0.000 claims description 8
238000006460 hydrolysis reaction Methods 0.000 claims description 8
CKJRKLKVCHMWLV-UHFFFAOYSA-N 2-(2-methoxyphenoxy)ethanamine Chemical compound COC1=CC=CC=C1OCCN CKJRKLKVCHMWLV-UHFFFAOYSA-N 0.000 claims description 7
ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical compound [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 7
239000011630 iodine Substances 0.000 claims description 7
229910052740 iodine Inorganic materials 0.000 claims description 7
238000004519 manufacturing process Methods 0.000 claims description 7
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 6
230000029936 alkylation Effects 0.000 claims description 5
238000005804 alkylation reaction Methods 0.000 claims description 5
125000004432 carbon atom Chemical group C* 0.000 claims description 5
125000001309 chloro group Chemical group Cl* 0.000 claims description 5
125000001424 substituent group Chemical group 0.000 claims description 5
FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 4
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 claims description 4
NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 4
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 4
BJEPYKJPYRNKOW-REOHCLBHSA-N (S)-malic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O BJEPYKJPYRNKOW-REOHCLBHSA-N 0.000 claims description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 claims description 2
GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 claims description 2
OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 2
KDYFGRWQOYBRFD-UHFFFAOYSA-N Succinic acid Natural products OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims description 2
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 2
230000002378 acidificating effect Effects 0.000 claims description 2
BJEPYKJPYRNKOW-UHFFFAOYSA-N alpha-hydroxysuccinic acid Natural products OC(=O)C(O)CC(O)=O BJEPYKJPYRNKOW-UHFFFAOYSA-N 0.000 claims description 2
229910000147 aluminium phosphate Inorganic materials 0.000 claims description 2
KDYFGRWQOYBRFD-NUQCWPJISA-N butanedioic acid Chemical compound O[14C](=O)CC[14C](O)=O KDYFGRWQOYBRFD-NUQCWPJISA-N 0.000 claims description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 claims description 2
239000001530 fumaric acid Substances 0.000 claims description 2
238000002955 isolation Methods 0.000 claims description 2
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 2
239000011976 maleic acid Substances 0.000 claims description 2
239000001630 malic acid Substances 0.000 claims description 2
235000011090 malic acid Nutrition 0.000 claims description 2
229910017604 nitric acid Inorganic materials 0.000 claims description 2
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims 7
FCSKOFQQCWLGMV-UHFFFAOYSA-N 5-{5-[2-chloro-4-(4,5-dihydro-1,3-oxazol-2-yl)phenoxy]pentyl}-3-methylisoxazole Chemical compound O1N=C(C)C=C1CCCCCOC1=CC=C(C=2OCCN=2)C=C1Cl FCSKOFQQCWLGMV-UHFFFAOYSA-N 0.000 claims 1
230000015572 biosynthetic process Effects 0.000 abstract description 26
238000003786 synthesis reaction Methods 0.000 abstract description 12
IAYPIBMASNFSPL-UHFFFAOYSA-N Ethylene oxide Chemical compound C1CO1 IAYPIBMASNFSPL-UHFFFAOYSA-N 0.000 abstract 1
NPAKNKYSJIDKMW-UHFFFAOYSA-N carvedilol Chemical compound COC1=CC=CC=C1OCCNCC(O)COC1=CC=CC2=NC3=CC=C[CH]C3=C12 NPAKNKYSJIDKMW-UHFFFAOYSA-N 0.000 abstract 1
231100001261 hazardous Toxicity 0.000 abstract 1
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 24
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
FEPNKMQKTQEEBZ-UHFFFAOYSA-N 1,3-dichloropropan-2-yl n-[2-(2-methoxyphenoxy)ethyl]carbamate Chemical compound COC1=CC=CC=C1OCCNC(=O)OC(CCl)CCl FEPNKMQKTQEEBZ-UHFFFAOYSA-N 0.000 description 16
239000000047 product Substances 0.000 description 15
ULCZPDWUOZBMRY-UHFFFAOYSA-N 5-(chloromethyl)-3-[2-(2-methoxyphenoxy)ethyl]-1,3-oxazolidin-2-one Chemical compound COC1=CC=CC=C1OCCN1C(=O)OC(CCl)C1 ULCZPDWUOZBMRY-UHFFFAOYSA-N 0.000 description 14
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 14
239000002585 base Substances 0.000 description 12
239000000203 mixture Substances 0.000 description 12
229910001868 water Inorganic materials 0.000 description 12
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
-1 2-[2'-methoxyphenoxy]-ethyl halide Chemical class 0.000 description 8
229910052736 halogen Inorganic materials 0.000 description 7
150000002367 halogens Chemical class 0.000 description 7
239000007858 starting material Substances 0.000 description 7
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 7
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 7
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 6
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
239000003480 eluent Substances 0.000 description 6
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 6
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 5
239000003153 chemical reaction reagent Substances 0.000 description 5
238000004128 high performance liquid chromatography Methods 0.000 description 5
239000007788 liquid Substances 0.000 description 5
238000000746 purification Methods 0.000 description 5
239000011541 reaction mixture Substances 0.000 description 5
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
238000000921 elemental analysis Methods 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
239000012071 phase Substances 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
238000010992 reflux Methods 0.000 description 4
239000012312 sodium hydride Substances 0.000 description 4
229910000104 sodium hydride Inorganic materials 0.000 description 4
238000005160 1H NMR spectroscopy Methods 0.000 description 3
SVWKIGRDISDRLO-UHFFFAOYSA-N 4-(oxiran-2-ylmethoxy)-9h-carbazole Chemical compound C=1C=CC=2NC3=CC=CC=C3C=2C=1OCC1CO1 SVWKIGRDISDRLO-UHFFFAOYSA-N 0.000 description 3
229910019142 PO4 Inorganic materials 0.000 description 3
238000006264 debenzylation reaction Methods 0.000 description 3
230000007613 environmental effect Effects 0.000 description 3
125000000466 oxiranyl group Chemical group 0.000 description 3
NBIIXXVUZAFLBC-UHFFFAOYSA-K phosphate Chemical compound [O-]P([O-])([O-])=O NBIIXXVUZAFLBC-UHFFFAOYSA-K 0.000 description 3
239000010452 phosphate Substances 0.000 description 3
238000007363 ring formation reaction Methods 0.000 description 3
DEWLEGDTCGBNGU-UHFFFAOYSA-N 1,3-dichloropropan-2-ol Chemical compound ClCC(O)CCl DEWLEGDTCGBNGU-UHFFFAOYSA-N 0.000 description 2
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 2
BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 2
YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
239000000538 analytical sample Substances 0.000 description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 2
229910052799 carbon Inorganic materials 0.000 description 2
238000004440 column chromatography Methods 0.000 description 2
239000003814 drug Substances 0.000 description 2
239000012442 inert solvent Substances 0.000 description 2
UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
239000002480 mineral oil Substances 0.000 description 2
235000010446 mineral oil Nutrition 0.000 description 2
229910052757 nitrogen Inorganic materials 0.000 description 2
239000012299 nitrogen atmosphere Substances 0.000 description 2
150000002924 oxiranes Chemical class 0.000 description 2
239000001301 oxygen Substances 0.000 description 2
229910052760 oxygen Inorganic materials 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
239000002243 precursor Substances 0.000 description 2
238000006798 ring closing metathesis reaction Methods 0.000 description 2
238000000926 separation method Methods 0.000 description 2
JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 2
239000007787 solid Substances 0.000 description 2
239000000725 suspension Substances 0.000 description 2
230000000304 vasodilatating effect Effects 0.000 description 2
IIWFWTZUDSPWTQ-UHFFFAOYSA-N 1,2-dichloropropan-2-yl phenyl carbonate Chemical compound C1(=CC=CC=C1)OC(OC(CCl)(Cl)C)=O IIWFWTZUDSPWTQ-UHFFFAOYSA-N 0.000 description 1
IFXQVNUAEAGXOV-UHFFFAOYSA-N 2-(2-methoxyphenoxy)acetaldehyde Chemical compound COC1=CC=CC=C1OCC=O IFXQVNUAEAGXOV-UHFFFAOYSA-N 0.000 description 1
KNWPXZOMSZABHD-UHFFFAOYSA-N 2-(2-methoxyphenoxy)ethanamine;hydrochloride Chemical compound Cl.COC1=CC=CC=C1OCCN KNWPXZOMSZABHD-UHFFFAOYSA-N 0.000 description 1
230000005526 G1 to G0 transition Effects 0.000 description 1
WYNCHZVNFNFDNH-UHFFFAOYSA-N Oxazolidine Chemical compound C1COCN1 WYNCHZVNFNFDNH-UHFFFAOYSA-N 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
239000012346 acetyl chloride Substances 0.000 description 1
125000003158 alcohol group Chemical group 0.000 description 1
238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
239000012080 ambient air Substances 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
230000003276 anti-hypertensive effect Effects 0.000 description 1
239000003963 antioxidant agent Substances 0.000 description 1
230000003078 antioxidant effect Effects 0.000 description 1
238000013459 approach Methods 0.000 description 1
239000008346 aqueous phase Substances 0.000 description 1
229910052786 argon Inorganic materials 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
235000015241 bacon Nutrition 0.000 description 1
230000009286 beneficial effect Effects 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
238000005574 benzylation reaction Methods 0.000 description 1
230000004071 biological effect Effects 0.000 description 1
230000000903 blocking effect Effects 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
239000007795 chemical reaction product Substances 0.000 description 1
238000013375 chromatographic separation Methods 0.000 description 1
238000009833 condensation Methods 0.000 description 1
230000005494 condensation Effects 0.000 description 1
238000001816 cooling Methods 0.000 description 1
229940079593 drug Drugs 0.000 description 1
230000000694 effects Effects 0.000 description 1
150000002148 esters Chemical class 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000001914 filtration Methods 0.000 description 1
239000012467 final product Substances 0.000 description 1
239000012458 free base Substances 0.000 description 1
239000000383 hazardous chemical Substances 0.000 description 1
239000013067 intermediate product Substances 0.000 description 1
238000011835 investigation Methods 0.000 description 1
239000000463 material Substances 0.000 description 1
229910052987 metal hydride Inorganic materials 0.000 description 1
150000004681 metal hydrides Chemical class 0.000 description 1
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
238000002156 mixing Methods 0.000 description 1
238000007040 multi-step synthesis reaction Methods 0.000 description 1
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 description 1
125000004433 nitrogen atom Chemical group N* 0.000 description 1
239000003921 oil Substances 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
125000000160 oxazolidinyl group Chemical group 0.000 description 1
AHWALFGBDFAJAI-UHFFFAOYSA-N phenyl carbonochloridate Chemical compound ClC(=O)OC1=CC=CC=C1 AHWALFGBDFAJAI-UHFFFAOYSA-N 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910052700 potassium Inorganic materials 0.000 description 1
125000006239 protecting group Chemical group 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
238000003756 stirring Methods 0.000 description 1
239000000126 substance Substances 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D263/00—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings
- C07D263/02—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings
- C07D263/08—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member
- C07D263/16—Heterocyclic compounds containing 1,3-oxazole or hydrogenated 1,3-oxazole rings not condensed with other rings having one double bond between ring members or between a ring member and a non-ring member with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D263/18—Oxygen atoms
- C07D263/20—Oxygen atoms attached in position 2
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/04—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups from amines with formation of carbamate groups
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/16—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C69/00—Esters of carboxylic acids; Esters of carbonic or haloformic acids
- C07C69/96—Esters of carbonic or haloformic acids
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/56—Ring systems containing three or more rings
- C07D209/80—[b, c]- or [b, d]-condensed
- C07D209/82—Carbazoles; Hydrogenated carbazoles
- C07D209/88—Carbazoles; Hydrogenated carbazoles with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to carbon atoms of the ring system
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D413/00—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms
- C07D413/02—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings
- C07D413/12—Heterocyclic compounds containing two or more hetero rings, at least one ring having nitrogen and oxygen atoms as the only ring hetero atoms containing two hetero rings linked by a chain containing hetero atoms as chain links

Landscapes

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

NO20025476A 2000-05-18 2002-11-15 Fremgangsmate og mellomprodukter for fremstilling av 1-(9H-karbazol-4-yloksy)-3-[2-(2-metoksyfenoksy)-etylamino]-propan-2-ol, karvedilol eller syreaddisjonssalter derav NO323828B1 (no)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
DK200000801A DK174645B1 (da)	2000-05-18	2000-05-18	Fremgangsmåde og mellemprodukter til fremstillingen af 1-(9H-carbazol-4-yloxy)-3-[2-(2-methoxy-phenoxy)-ethylamino]-propan-2-ol, carvedilol og syreadditionssalte deraf
PCT/DK2001/000306 WO2001087837A1 (en)	2000-05-18	2001-05-03	Process and intermediates for the preparation of 1-(9h-carbazol-4-yloxy)-3-[2-(2-methoxy-phenoxy)-ethylamino]-propan-2-ol, carvedilol or acid addition salts thereof

Publications (3)

Publication Number	Publication Date
NO20025476L NO20025476L (no)	2002-11-15
NO20025476D0 NO20025476D0 (no)	2002-11-15
NO323828B1 true NO323828B1 (no)	2007-07-09

Family

ID=8159503

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
NO20025476A NO323828B1 (no)	2000-05-18	2002-11-15	Fremgangsmate og mellomprodukter for fremstilling av 1-(9H-karbazol-4-yloksy)-3-[2-(2-metoksyfenoksy)-etylamino]-propan-2-ol, karvedilol eller syreaddisjonssalter derav

Country Status (8)

Country	Link
EP (3)	EP1367052B1 (de)
AT (3)	ATE322481T1 (de)
CA (1)	CA2407103A1 (de)
DK (4)	DK174645B1 (de)
ES (3)	ES2268275T3 (de)
NO (1)	NO323828B1 (de)
PT (3)	PT1375474E (de)
WO (1)	WO2001087837A1 (de)

Families Citing this family (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
AU2003251627A1 (en)	2002-06-27	2004-01-19	Sb Pharmco Puerto Rico Inc.	Carvedilol hydrobromide
MXPA04012923A (es) *	2002-06-27	2005-03-31	Sb Pharmco Inc	Sales de fosfato de carvedilol y/o solvatos de las mismas, composiciones correspondientes y/o metodos de tratamiento.
WO2004094378A1 (en)	2003-04-21	2004-11-04	Matrix Laboratories Ltd	Process for the preparation of carvedilol form-ii
JP2007512372A (ja) *	2003-11-25	2007-05-17	エスビー・ファルムコ・プエルト・リコ・インコーポレイテッド	カルベジロール塩、対応する組成物、送達および／または治療方法
KR100746455B1 (ko) *	2006-02-23	2007-08-03	안국약품 주식회사	고광학순도의 키랄 카베딜롤의 제조방법

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3152168A (en) *	1961-09-05	1964-10-06	Monsanto Co	Haloalkyl pentahalophenyl carbonates
DE2815926A1 (de) *	1978-04-13	1979-10-18	Boehringer Mannheim Gmbh	Neue carbazolyl-(4)-oxy-propanolamin-derivate, verfahren zu ihrer herstellung und diese verbindungen enthaltende arzneimittel
FR2506769A2 (fr) *	1978-06-09	1982-12-03	Delalande Sa	Para-((cyano-5 n pentyl-1) phenyl)-3 methoxymethyl-5 oxazolidinone-2, son procede de preparation et ses applications en therapeutique
HU227441B1 (en) *	1997-11-24	2011-06-28	Egis Gyogyszergyar Nyilvanosan Muekoedoe Reszvenytarsasag	Process for producing carvedilol, enantiomers and salts thereof

2000
- 2000-05-18 DK DK200000801A patent/DK174645B1/da not_active IP Right Cessation
2001
- 2001-05-03 CA CA002407103A patent/CA2407103A1/en not_active Abandoned
- 2001-05-03 EP EP03077684A patent/EP1367052B1/de not_active Expired - Lifetime
- 2001-05-03 EP EP03077677A patent/EP1375474B1/de not_active Expired - Lifetime
- 2001-05-03 EP EP01929337A patent/EP1282601B1/de not_active Expired - Lifetime
- 2001-05-03 AT AT03077677T patent/ATE322481T1/de not_active IP Right Cessation
- 2001-05-03 DK DK03077684T patent/DK1367052T3/da active
- 2001-05-03 DK DK01929337T patent/DK1282601T3/da active
- 2001-05-03 PT PT03077677T patent/PT1375474E/pt unknown
- 2001-05-03 ES ES03077684T patent/ES2268275T3/es not_active Expired - Lifetime
- 2001-05-03 AT AT01929337T patent/ATE258165T1/de not_active IP Right Cessation
- 2001-05-03 PT PT01929337T patent/PT1282601E/pt unknown
- 2001-05-03 ES ES03077677T patent/ES2260575T3/es not_active Expired - Lifetime
- 2001-05-03 DK DK03077677T patent/DK1375474T3/da active
- 2001-05-03 PT PT03077684T patent/PT1367052E/pt unknown
- 2001-05-03 WO PCT/DK2001/000306 patent/WO2001087837A1/en not_active Ceased
- 2001-05-03 ES ES01929337T patent/ES2214414T3/es not_active Expired - Lifetime
- 2001-05-03 AT AT03077684T patent/ATE332892T1/de not_active IP Right Cessation
2002
- 2002-11-15 NO NO20025476A patent/NO323828B1/no unknown

Also Published As

Publication number	Publication date
EP1367052B1 (de)	2006-07-12
EP1375474A3 (de)	2004-10-06
ES2268275T3 (es)	2007-03-16
ATE258165T1 (de)	2004-02-15
EP1375474A2 (de)	2004-01-02
NO20025476L (no)	2002-11-15
EP1367052A2 (de)	2003-12-03
ATE332892T1 (de)	2006-08-15
PT1282601E (pt)	2004-06-30
EP1282601B1 (de)	2004-01-21
DK1282601T3 (da)	2004-05-24
NO20025476D0 (no)	2002-11-15
EP1375474B1 (de)	2006-04-05
ATE322481T1 (de)	2006-04-15
EP1282601A1 (de)	2003-02-12
CA2407103A1 (en)	2001-11-22
PT1375474E (pt)	2006-07-31
PT1367052E (pt)	2006-10-31
EP1367052A3 (de)	2003-12-10
DK1375474T3 (da)	2006-08-07
ES2214414T3 (es)	2004-09-16
DK1367052T3 (da)	2006-09-25
DK174645B1 (da)	2003-08-04
DK200000801A (da)	2001-11-19
ES2260575T3 (es)	2006-11-01
WO2001087837A1 (en)	2001-11-22

Publication	Publication Date	Title
CN104447445B (zh)	2016-07-06	一种合成阿普斯特中间体的制备方法
US11780810B2 (en)	2023-10-10	Intermediates for optically active piperidine derivatives and preparation methods thereof
CN118812481A (zh)	2024-10-22	杂环亚基乙酰胺衍生物的制造方法
US10428012B2 (en)	2019-10-01	Method of preparation of 4-isopropylamino-1-butanol
CN112661668B (zh)	2023-07-28	一种n-取代酰胺类化合物及其制备方法
EP1367052B1 (de)	2006-07-12	Zwischenverbindung für die Herstellung von Carvedilol
CN112824381B (zh)	2024-04-26	一种哌啶胺的制备方法
EP0123832B1 (de)	1987-11-19	Verfahren zur optischen Trennung einer Enantiomer-Mischung von Trans-3-((4-Methoxyphenoxy)-Methyl)-1-Methyl-4-Phenyl-Piperidin
TW460440B (en)	2001-10-21	A process for preparing A 3-amino-2-hydroxy-1-propyl ether
AU2017333054B2 (en)	2019-11-21	Method for preparing phenylalanine compound
JPH05506008A (ja)	1993-09-02	ホモキラルなアミンの製造方法、該アミンを製造するための中間体の製造方法及び該方法に従って製造された中間体
EP0125053B1 (de)	1986-09-17	Verfahren zur Herstellung sekundärer Amine
CN110724098A (zh)	2020-01-24	一种5,7-二氯-1,2,3,4-四氢异喹啉-6-羧酸盐酸盐的合成方法
NO160656B (no)	1989-02-06	Fremgangsm te for fremstilling av 1-((3,4-dimetoksy)amino)-3-(m-tolyloksy)-2-propanol.
WO2007132990A1 (en)	2007-11-22	Process for the preparation of chiral glycidylphthalimide in highly optical purity
JP4671091B2 (ja)	2011-04-13	１−置換−２−メチルピペラジンの製造方法
CA2217880C (en)	2004-02-24	Synthesis of optically active aminoindanol
JPWO2005000810A1 (ja)	2006-10-19	含窒素複素環化合物の製造方法
JPS63112543A (ja)	1988-05-17	アルコキシカルボニル置換フエノキシエチルアミン類の製造方法
EP3845518A1 (de)	2021-07-07	Verfahren zur herstellung von (1r,3s)-3-amino-1-cyclopentanol und salze davon
JPH0440355B2 (de)	1992-07-02
JP2005281168A (ja)	2005-10-13	３−ピロリジノールの製造法
HU226683B1 (en)	2009-06-29	Intermediat product of fluoxetine and process for its production
JP2007008827A (ja)	2007-01-18	末端にヘテロ芳香族置換基を有する光学活性モノアミノトリエステル誘導体の製造法
WO2007037242A1 (ja)	2007-04-05	光学活性ベンジルアミン誘導体の製造方法