SK284366B6 - Deriváty 6-(4-fenylbutoxy)hexylamínu, spôsob jeho prípravy a spôsob prípravy salmeterolu - Google Patents

Deriváty 6-(4-fenylbutoxy)hexylamínu, spôsob jeho prípravy a spôsob prípravy salmeterolu Download PDF

Info

Publication number: SK284366B6
Authority: SK; Slovakia
Prior art keywords: group; formula; compound; benzyl; process according
Prior art date: 1998-09-28

Application number

SK386-2001A

Other languages

English (en)

Slovak (sk)

Other versions

SK3862001A3 (en

Inventor

Bellmunt Jordi Bessa

Barjoan Pere Dalmases

Olondriz Francisco Marquillas

Original Assignee

Vita Cientifica

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.)

1998-09-28

Filing date

1999-09-20

Publication date

2005-02-04

1999-09-20 Application filed by Vita Cientifica filed Critical Vita Cientifica

2002-09-10 Publication of SK3862001A3 publication Critical patent/SK3862001A3/sk

2005-02-04 Publication of SK284366B6 publication Critical patent/SK284366B6/sk

Links

238000000034 method Methods 0.000 title claims abstract description 35
GIIZNNXWQWCKIB-UHFFFAOYSA-N Serevent Chemical compound C1=C(O)C(CO)=CC(C(O)CNCCCCCCOCCCCC=2C=CC=CC=2)=C1 GIIZNNXWQWCKIB-UHFFFAOYSA-N 0.000 title claims abstract description 19
229960004017 salmeterol Drugs 0.000 title claims abstract description 18
238000002360 preparation method Methods 0.000 title claims abstract description 14
GNSOSZKMHANCMP-UHFFFAOYSA-N 6-(4-phenylbutoxy)hexan-1-amine Chemical class NCCCCCCOCCCCC1=CC=CC=C1 GNSOSZKMHANCMP-UHFFFAOYSA-N 0.000 title claims abstract description 13
150000001875 compounds Chemical class 0.000 claims abstract description 27
-1 cyclic acetals Chemical class 0.000 claims abstract description 26
125000002252 acyl group Chemical group 0.000 claims abstract description 19
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 19
125000005098 aryl alkoxy carbonyl group Chemical group 0.000 claims abstract description 19
125000005161 aryl oxy carbonyl group Chemical group 0.000 claims abstract description 19
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims abstract description 16
125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 10
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 10
150000002902 organometallic compounds Chemical class 0.000 claims abstract description 4
150000003839 salts Chemical class 0.000 claims abstract description 4
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 48
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 33
RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 30
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 22
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 22
238000006243 chemical reaction Methods 0.000 claims description 22
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 19
ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 19
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 18
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 15
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 15
125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 13
239000012442 inert solvent Substances 0.000 claims description 13
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 11
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 10
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 9
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 8
229910052739 hydrogen Inorganic materials 0.000 claims description 8
239000001257 hydrogen Substances 0.000 claims description 8
230000007062 hydrolysis Effects 0.000 claims description 8
238000006460 hydrolysis reaction Methods 0.000 claims description 8
239000002904 solvent Substances 0.000 claims description 7
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 6
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 6
150000001412 amines Chemical class 0.000 claims description 6
150000007530 organic bases Chemical class 0.000 claims description 6
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 5
230000029936 alkylation Effects 0.000 claims description 5
238000005804 alkylation reaction Methods 0.000 claims description 5
238000009835 boiling Methods 0.000 claims description 5
239000003054 catalyst Substances 0.000 claims description 5
150000007529 inorganic bases Chemical class 0.000 claims description 5
150000002576 ketones Chemical class 0.000 claims description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 4
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 4
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 4
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 4
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 4
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 4
229910052794 bromium Inorganic materials 0.000 claims description 4
239000003153 chemical reaction reagent Substances 0.000 claims description 4
229910052801 chlorine Inorganic materials 0.000 claims description 4
239000000460 chlorine Substances 0.000 claims description 4
150000002148 esters Chemical class 0.000 claims description 4
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
238000005984 hydrogenation reaction Methods 0.000 claims description 4
238000007327 hydrogenolysis reaction Methods 0.000 claims description 4
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 4
150000007522 mineralic acids Chemical class 0.000 claims description 4
150000007524 organic acids Chemical class 0.000 claims description 4
238000003420 transacetalization reaction Methods 0.000 claims description 4
RPLSBADGISFNSI-UHFFFAOYSA-N 2,2-dimethyl-1,3-dioxane Chemical compound CC1(C)OCCCO1 RPLSBADGISFNSI-UHFFFAOYSA-N 0.000 claims description 3
HDGHQFQMWUTHKL-UHFFFAOYSA-N 2-methyl-1,3-dioxane Chemical compound CC1OCCCO1 HDGHQFQMWUTHKL-UHFFFAOYSA-N 0.000 claims description 3
COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 claims description 3
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims description 3
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 3
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 3
125000003277 amino group Chemical group 0.000 claims description 3
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 3
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 3
239000003795 chemical substances by application Substances 0.000 claims description 3
125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 3
229910052744 lithium Inorganic materials 0.000 claims description 3
239000011777 magnesium Substances 0.000 claims description 3
229910052749 magnesium Inorganic materials 0.000 claims description 3
UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 3
125000004044 trifluoroacetyl group Chemical group FC(C(=O)*)(F)F 0.000 claims description 3
150000000093 1,3-dioxanes Chemical class 0.000 claims description 2
WNXJIVFYUVYPPR-UHFFFAOYSA-N 1,3-dioxolane Chemical compound C1COCO1 WNXJIVFYUVYPPR-UHFFFAOYSA-N 0.000 claims description 2
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
BVKZGUZCCUSVTD-UHFFFAOYSA-M Bicarbonate Chemical compound OC([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-M 0.000 claims description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-L Carbonate Chemical compound [O-]C([O-])=O BVKZGUZCCUSVTD-UHFFFAOYSA-L 0.000 claims description 2
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 claims description 2
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 2
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 2
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
125000004036 acetal group Chemical group 0.000 claims description 2
150000008064 anhydrides Chemical class 0.000 claims description 2
150000004982 aromatic amines Chemical class 0.000 claims description 2
150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 2
MJSHDCCLFGOEIK-UHFFFAOYSA-N benzyl (2,5-dioxopyrrolidin-1-yl) carbonate Chemical compound O=C1CCC(=O)N1OC(=O)OCC1=CC=CC=C1 MJSHDCCLFGOEIK-UHFFFAOYSA-N 0.000 claims description 2
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 claims description 2
FHRRJZZGSJXPRQ-UHFFFAOYSA-N benzyl phenylmethoxycarbonyl carbonate Chemical compound C=1C=CC=CC=1COC(=O)OC(=O)OCC1=CC=CC=C1 FHRRJZZGSJXPRQ-UHFFFAOYSA-N 0.000 claims description 2
125000004432 carbon atom Chemical group C* 0.000 claims description 2
229910052802 copper Inorganic materials 0.000 claims description 2
239000010949 copper Substances 0.000 claims description 2
ZFTFAPZRGNKQPU-UHFFFAOYSA-N dicarbonic acid Chemical class OC(=O)OC(O)=O ZFTFAPZRGNKQPU-UHFFFAOYSA-N 0.000 claims description 2
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 claims description 2
238000004519 manufacturing process Methods 0.000 claims description 2
229910052751 metal Inorganic materials 0.000 claims description 2
239000002184 metal Substances 0.000 claims description 2
229910052763 palladium Inorganic materials 0.000 claims description 2
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 2
DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 claims description 2
UJJDEOLXODWCGK-UHFFFAOYSA-N tert-butyl carbonochloridate Chemical compound CC(C)(C)OC(Cl)=O UJJDEOLXODWCGK-UHFFFAOYSA-N 0.000 claims description 2
150000003512 tertiary amines Chemical class 0.000 claims description 2
239000008096 xylene Substances 0.000 claims description 2
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 claims 3
JLTDJTHDQAWBAV-UHFFFAOYSA-N N,N-dimethylaniline Chemical compound CN(C)C1=CC=CC=C1 JLTDJTHDQAWBAV-UHFFFAOYSA-N 0.000 claims 2
150000002170 ethers Chemical class 0.000 claims 2
125000006091 1,3-dioxolane group Chemical class 0.000 claims 1
AOGYCOYQMAVAFD-UHFFFAOYSA-N chlorocarbonic acid Chemical class OC(Cl)=O AOGYCOYQMAVAFD-UHFFFAOYSA-N 0.000 claims 1
229940043279 diisopropylamine Drugs 0.000 claims 1
125000001033 ether group Chemical group 0.000 claims 1
230000003301 hydrolyzing effect Effects 0.000 claims 1
239000003960 organic solvent Substances 0.000 claims 1
125000004169 (C1-C6) alkyl group Chemical group 0.000 abstract 1
239000000203 mixture Substances 0.000 description 19
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
125000006239 protecting group Chemical group 0.000 description 10
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
239000012074 organic phase Substances 0.000 description 7
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
150000002118 epoxides Chemical class 0.000 description 5
230000002829 reductive effect Effects 0.000 description 5
238000003756 stirring Methods 0.000 description 5
HYRIAERKUPZOCS-UHFFFAOYSA-N 4-(6-bromohexoxy)butylbenzene Chemical compound BrCCCCCCOCCCCC1=CC=CC=C1 HYRIAERKUPZOCS-UHFFFAOYSA-N 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
WHDNTMUSIDMLHG-UHFFFAOYSA-N benzyl n-(2-oxoethyl)-n-[6-(4-phenylbutoxy)hexyl]carbamate Chemical compound C=1C=CC=CC=1COC(=O)N(CC=O)CCCCCCOCCCCC1=CC=CC=C1 WHDNTMUSIDMLHG-UHFFFAOYSA-N 0.000 description 4
WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 4
239000012043 crude product 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
239000000741 silica gel Substances 0.000 description 4
229910002027 silica gel Inorganic materials 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 3
UIALGZOSKLCMHF-UHFFFAOYSA-N 6-bromo-2,2-dimethyl-4h-1,3-benzodioxine Chemical compound BrC1=CC=C2OC(C)(C)OCC2=C1 UIALGZOSKLCMHF-UHFFFAOYSA-N 0.000 description 3
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
150000001299 aldehydes Chemical class 0.000 description 3
NHZPWFUYBUSPHT-UHFFFAOYSA-N benzyl n-(2,2-dimethoxyethyl)-n-[6-(4-phenylbutoxy)hexyl]carbamate Chemical compound C=1C=CC=CC=1COC(=O)N(CC(OC)OC)CCCCCCOCCCCC1=CC=CC=C1 NHZPWFUYBUSPHT-UHFFFAOYSA-N 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
150000002431 hydrogen Chemical class 0.000 description 3
239000000543 intermediate Substances 0.000 description 3
UTTFDCWJAKGSQZ-UHFFFAOYSA-N n-(2,2-diethoxyethyl)-6-(4-phenylbutoxy)hexan-1-amine Chemical compound CCOC(OCC)CNCCCCCCOCCCCC1=CC=CC=C1 UTTFDCWJAKGSQZ-UHFFFAOYSA-N 0.000 description 3
RRYAWKSPDXOGLM-UHFFFAOYSA-N n-(2,2-dimethoxyethyl)-6-(4-phenylbutoxy)hexan-1-amine;hydrobromide Chemical compound Br.COC(OC)CNCCCCCCOCCCCC1=CC=CC=C1 RRYAWKSPDXOGLM-UHFFFAOYSA-N 0.000 description 3
239000011541 reaction mixture Substances 0.000 description 3
229910052938 sodium sulfate Inorganic materials 0.000 description 3
235000011152 sodium sulphate Nutrition 0.000 description 3
239000007858 starting material Substances 0.000 description 3
NMPVEAUIHMEAQP-UHFFFAOYSA-N 2-Bromoacetaldehyde Chemical compound BrCC=O NMPVEAUIHMEAQP-UHFFFAOYSA-N 0.000 description 2
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 2
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
125000000217 alkyl group Chemical group 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
SXDOZUBVNVZPCM-UHFFFAOYSA-N benzyl n-(2,2-diethoxyethyl)-n-[6-(4-phenylbutoxy)hexyl]carbamate Chemical compound C=1C=CC=CC=1COC(=O)N(CC(OCC)OCC)CCCCCCOCCCCC1=CC=CC=C1 SXDOZUBVNVZPCM-UHFFFAOYSA-N 0.000 description 2
239000006227 byproduct Substances 0.000 description 2
238000004821 distillation Methods 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
150000003944 halohydrins Chemical class 0.000 description 2
AFVFQIVMOAPDHO-UHFFFAOYSA-N methanesulfonic acid Substances CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 2
JWLIKZBRVQRFNF-UHFFFAOYSA-N n-benzyl-6-(4-phenylbutoxy)hexan-1-amine Chemical compound C=1C=CC=CC=1CNCCCCCCOCCCCC1=CC=CC=C1 JWLIKZBRVQRFNF-UHFFFAOYSA-N 0.000 description 2
OUAYLCUKLZVMPS-UHFFFAOYSA-N n-benzyl-6-(4-phenylbutoxy)hexan-1-amine;hydrobromide Chemical compound Br.C=1C=CC=CC=1CNCCCCCCOCCCCC1=CC=CC=C1 OUAYLCUKLZVMPS-UHFFFAOYSA-N 0.000 description 2
KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
239000000725 suspension Substances 0.000 description 2
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
DNIAPMSPPWPWGF-GSVOUGTGSA-N (R)-(-)-Propylene glycol Chemical compound C[C@@H](O)CO DNIAPMSPPWPWGF-GSVOUGTGSA-N 0.000 description 1
DHKHKXVYLBGOIT-UHFFFAOYSA-N 1,1-Diethoxyethane Chemical compound CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 1
PAAZPARNPHGIKF-UHFFFAOYSA-N 1,2-dibromoethane Chemical compound BrCCBr PAAZPARNPHGIKF-UHFFFAOYSA-N 0.000 description 1
150000005530 1,2-dioxolanes Chemical class 0.000 description 1
VDFVNEFVBPFDSB-UHFFFAOYSA-N 1,3-dioxane Chemical compound C1COCOC1 VDFVNEFVBPFDSB-UHFFFAOYSA-N 0.000 description 1
SGRHVVLXEBNBDV-UHFFFAOYSA-N 1,6-dibromohexane Chemical compound BrCCCCCCBr SGRHVVLXEBNBDV-UHFFFAOYSA-N 0.000 description 1
OYCVIHNVPFDNLD-UHFFFAOYSA-N 1-(2,2-dimethyl-4h-1,3-benzodioxin-6-yl)-2-[6-(4-phenylbutoxy)hexylamino]ethanol Chemical compound C=1C=C2OC(C)(C)OCC2=CC=1C(O)CNCCCCCCOCCCCC1=CC=CC=C1 OYCVIHNVPFDNLD-UHFFFAOYSA-N 0.000 description 1
QKWWDTYDYOFRJL-UHFFFAOYSA-N 2,2-dimethoxyethanamine Chemical compound COC(CN)OC QKWWDTYDYOFRJL-UHFFFAOYSA-N 0.000 description 1
LILXDMFJXYAKMK-UHFFFAOYSA-N 2-bromo-1,1-diethoxyethane Chemical compound CCOC(CBr)OCC LILXDMFJXYAKMK-UHFFFAOYSA-N 0.000 description 1
KNKRHSVKIORZQB-UHFFFAOYSA-N 4-bromo-2-(hydroxymethyl)phenol Chemical compound OCC1=CC(Br)=CC=C1O KNKRHSVKIORZQB-UHFFFAOYSA-N 0.000 description 1
LDZLXQFDGRCELX-UHFFFAOYSA-N 4-phenylbutan-1-ol Chemical compound OCCCCC1=CC=CC=C1 LDZLXQFDGRCELX-UHFFFAOYSA-N 0.000 description 1
101100294106 Caenorhabditis elegans nhr-3 gene Proteins 0.000 description 1
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
MHZGKXUYDGKKIU-UHFFFAOYSA-N Decylamine Chemical compound CCCCCCCCCCN MHZGKXUYDGKKIU-UHFFFAOYSA-N 0.000 description 1
239000005909 Kieselgur Substances 0.000 description 1
YZDHUMDUHIAGDG-UHFFFAOYSA-N N-(2,2-diethoxyethyl)-5-(4-phenylbutoxy)hexan-1-amine Chemical compound CCOC(OCC)CNCCCCC(C)OCCCCC1=CC=CC=C1 YZDHUMDUHIAGDG-UHFFFAOYSA-N 0.000 description 1
LUNDKKXHGUCOSP-UHFFFAOYSA-N N-(4-phenylbutoxy)hexan-1-amine Chemical compound C1(=CC=CC=C1)CCCCONCCCCCC LUNDKKXHGUCOSP-UHFFFAOYSA-N 0.000 description 1
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
239000002253 acid Substances 0.000 description 1
230000002378 acidificating effect Effects 0.000 description 1
239000002168 alkylating agent Substances 0.000 description 1
229940100198 alkylating agent Drugs 0.000 description 1
150000001408 amides Chemical class 0.000 description 1
239000000010 aprotic solvent Substances 0.000 description 1
125000003118 aryl group Chemical group 0.000 description 1
208000006673 asthma Diseases 0.000 description 1
238000011914 asymmetric synthesis Methods 0.000 description 1
239000002585 base Substances 0.000 description 1
UTZLYIFQYGQUPA-UHFFFAOYSA-N benzyl 2,5-dioxopyrrolidine-1-carboxylate Chemical compound O=C1CCC(=O)N1C(=O)OCC1=CC=CC=C1 UTZLYIFQYGQUPA-UHFFFAOYSA-N 0.000 description 1
ZMYLKHCNPQKIIG-UHFFFAOYSA-N benzyl n-[2-(2,2-dimethyl-4h-1,3-benzodioxin-6-yl)-2-hydroxyethyl]-n-[6-(4-phenylbutoxy)hexyl]carbamate Chemical compound C=1C=C2OC(C)(C)OCC2=CC=1C(O)CN(C(=O)OCC=1C=CC=CC=1)CCCCCCOCCCCC1=CC=CC=C1 ZMYLKHCNPQKIIG-UHFFFAOYSA-N 0.000 description 1
230000031709 bromination Effects 0.000 description 1
238000005893 bromination reaction Methods 0.000 description 1
229940124630 bronchodilator Drugs 0.000 description 1
229910052799 carbon Inorganic materials 0.000 description 1
125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
230000003197 catalytic effect Effects 0.000 description 1
FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 description 1
238000007265 chloromethylation reaction Methods 0.000 description 1
229940125904 compound 1 Drugs 0.000 description 1
238000007796 conventional method Methods 0.000 description 1
238000006264 debenzylation reaction Methods 0.000 description 1
125000000950 dibromo group Chemical group Br* 0.000 description 1
238000001914 filtration Methods 0.000 description 1
VZCYOOQTPOCHFL-OWOJBTEDSA-L fumarate(2-) Chemical compound [O-]C(=O)\C=C\C([O-])=O VZCYOOQTPOCHFL-OWOJBTEDSA-L 0.000 description 1
229910052736 halogen Inorganic materials 0.000 description 1
150000002367 halogens Chemical class 0.000 description 1
SHFJWMWCIHQNCP-UHFFFAOYSA-M hydron;tetrabutylazanium;sulfate Chemical compound OS([O-])(=O)=O.CCCC[N+](CCCC)(CCCC)CCCC SHFJWMWCIHQNCP-UHFFFAOYSA-M 0.000 description 1
238000002955 isolation Methods 0.000 description 1
VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 1
125000000896 monocarboxylic acid group Chemical group 0.000 description 1
LEWCIOCPODWLKH-UHFFFAOYSA-N n-benzyl-n-(2,2-diethoxyethyl)-6-(4-phenylbutoxy)hexan-1-amine Chemical compound C=1C=CC=CC=1CN(CC(OCC)OCC)CCCCCCOCCCCC1=CC=CC=C1 LEWCIOCPODWLKH-UHFFFAOYSA-N 0.000 description 1
150000002828 nitro derivatives Chemical class 0.000 description 1
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
239000012044 organic layer Substances 0.000 description 1
125000002524 organometallic group Chemical group 0.000 description 1
239000012071 phase Substances 0.000 description 1
238000011084 recovery Methods 0.000 description 1
238000006722 reduction reaction Methods 0.000 description 1
238000006268 reductive amination reaction Methods 0.000 description 1
238000010992 reflux Methods 0.000 description 1
238000000926 separation method Methods 0.000 description 1
238000010898 silica gel chromatography Methods 0.000 description 1
230000001225 therapeutic effect Effects 0.000 description 1

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D319/00—Heterocyclic compounds containing six-membered rings having two oxygen atoms as the only ring hetero atoms
- C07D319/04—1,3-Dioxanes; Hydrogenated 1,3-dioxanes
- C07D319/08—1,3-Dioxanes; Hydrogenated 1,3-dioxanes condensed with carbocyclic rings or ring systems
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P11/00—Drugs for disorders of the respiratory system
- A61P11/08—Bronchodilators
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C213/00—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton
- C07C213/08—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions not involving the formation of amino groups, hydroxy groups or etherified or esterified hydroxy groups
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C217/28—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C217/00—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton
- C07C217/02—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C217/04—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated
- C07C217/28—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines
- C07C217/40—Compounds containing amino and etherified hydroxy groups bound to the same carbon skeleton having etherified hydroxy groups and amino groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton being acyclic and saturated having one amino group and at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the carbon skeleton, e.g. ethers of polyhydroxy amines having at least two singly-bound oxygen atoms, with at least one being part of an etherified hydroxy group, bound to the same carbon atom of the carbon skeleton, e.g. amino-ketals, ortho esters
- 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
- 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)
Health & Medical Sciences (AREA)
Chemical Kinetics & Catalysis (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
Life Sciences & Earth Sciences (AREA)
General Chemical & Material Sciences (AREA)
Medicinal Chemistry (AREA)
Bioinformatics & Cheminformatics (AREA)
Engineering & Computer Science (AREA)
Pharmacology & Pharmacy (AREA)
Pulmonology (AREA)
Animal Behavior & Ethology (AREA)
General Health & Medical Sciences (AREA)
Public Health (AREA)
Veterinary Medicine (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)

SK386-2001A 1998-09-28 1999-09-20 Deriváty 6-(4-fenylbutoxy)hexylamínu, spôsob jeho prípravy a spôsob prípravy salmeterolu SK284366B6 (sk)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
ES009802014A ES2142771B1 (es)	1998-09-28	1998-09-28	Nuevos derivados de la 6-(4-fenil-butoxi) hexilamina y procedimiento para la obtencion de salmeterol.
PCT/ES1999/000294 WO2000018722A2 (es)	1998-09-28	1999-09-20	Nuevos derivados de la 6-(4-fenilbutoxi)hexilamina y procedimiento para la obtencion de salmeterol

Publications (2)

Publication Number	Publication Date
SK3862001A3 SK3862001A3 (en)	2002-09-10
SK284366B6 true SK284366B6 (sk)	2005-02-04

Family

ID=8305274

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
SK386-2001A SK284366B6 (sk)	1998-09-28	1999-09-20	Deriváty 6-(4-fenylbutoxy)hexylamínu, spôsob jeho prípravy a spôsob prípravy salmeterolu

Country Status (24)

Country	Link
US (1)	US6388134B1 (pl)
EP (1)	EP1132373B1 (pl)
JP (1)	JP3786834B2 (pl)
KR (1)	KR100479256B1 (pl)
CN (1)	CN1189446C (pl)
AT (1)	ATE254596T1 (pl)
AU (1)	AU756042B2 (pl)
BR (1)	BR9913989A (pl)
CA (1)	CA2344647C (pl)
CZ (2)	CZ296902B6 (pl)
DE (1)	DE69912984D1 (pl)
EA (1)	EA003397B1 (pl)
ES (2)	ES2142771B1 (pl)
HU (1)	HUP0103969A3 (pl)
IL (1)	IL141991A (pl)
IS (1)	IS2016B (pl)
NO (2)	NO327780B1 (pl)
NZ (1)	NZ511157A (pl)
OA (1)	OA11660A (pl)
PL (1)	PL196116B1 (pl)
PT (1)	PT1132373E (pl)
SK (1)	SK284366B6 (pl)
TR (1)	TR200100862T2 (pl)
WO (1)	WO2000018722A2 (pl)

Families Citing this family (9)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
DE10209583B4 (de) *	2002-03-05	2006-01-19	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Verfahren zur Herstellung von 4-(6-Bromhexyloxy)-butylbenzol
US6835857B2 (en)	2002-03-05	2004-12-28	Boehringer Ingelheim Pharma Gmbh & Co. Kg	Process for the manufacture of 4-(6-bromohexyloxy)-butylbenzene
CA2625337C (en) *	2005-10-17	2014-03-18	Vinayak G. Gore	Novel process
ES2288114B1 (es) *	2006-04-26	2008-12-01	Quimica Sintetica S.A.	Nuevo procedimiento de sintesis de (6-(4-fenilbutoxi)hexil)aminas n-sustituidas y su uso en la sintesis de salmeterol xinafoato.
EP2127641A1 (en)	2008-05-26	2009-12-02	Inke, S.A.	Micronisable form of salmeterol xinafoate
CN101712622B (zh) *	2009-11-10	2012-10-03	浙江万里学院	抗哮喘药物沙美特罗的制备方法
CN103435505A (zh) *	2013-09-05	2013-12-11	南京工业大学	一种合成(r)-沙美特罗的方法
US9447067B2 (en) *	2014-10-03	2016-09-20	Amphastar Pahmaceuticals, Inc.	Method of preparing intermediate of salmeterol
KR20230001708U (ko)	2022-02-17	2023-08-24	유기택	재접착식 슬림 평면형 액자

Family Cites Families (3)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
ZW6584A1 (en) *	1983-04-18	1985-04-17	Glaxo Group Ltd	Phenethanolamine derivatives
EP0162576B1 (en) *	1984-04-17	1989-07-26	Glaxo Group Limited	Ethanolamine compounds
ES2065269B1 (es) *	1993-05-11	1995-10-01	S A L V A T Lab Sa	6-(4-(fenilbutoxi) hexilaminometil-4-hidroxi-a1,a3-bencenodimetanol. procedimiento para la obtencion del mismo y nuevos intermedios utilizados en su preparacion.

1998
- 1998-09-28 ES ES009802014A patent/ES2142771B1/es not_active Expired - Fee Related
1999
- 1999-09-20 AU AU59839/99A patent/AU756042B2/en not_active Ceased
- 1999-09-20 CA CA002344647A patent/CA2344647C/en not_active Expired - Fee Related
- 1999-09-20 PT PT99969711T patent/PT1132373E/pt unknown
- 1999-09-20 IL IL14199199A patent/IL141991A/en not_active IP Right Cessation
- 1999-09-20 EA EA200100391A patent/EA003397B1/ru not_active IP Right Cessation
- 1999-09-20 AT AT99969711T patent/ATE254596T1/de not_active IP Right Cessation
- 1999-09-20 DE DE69912984T patent/DE69912984D1/de not_active Expired - Lifetime
- 1999-09-20 TR TR2001/00862T patent/TR200100862T2/xx unknown
- 1999-09-20 ES ES99969711T patent/ES2212672T3/es not_active Expired - Lifetime
- 1999-09-20 EP EP99969711A patent/EP1132373B1/en not_active Expired - Lifetime
- 1999-09-20 CZ CZ20033118A patent/CZ296902B6/cs not_active IP Right Cessation
- 1999-09-20 NZ NZ511157A patent/NZ511157A/xx not_active IP Right Cessation
- 1999-09-20 US US09/806,538 patent/US6388134B1/en not_active Expired - Lifetime
- 1999-09-20 OA OA1200100079A patent/OA11660A/en unknown
- 1999-09-20 PL PL348572A patent/PL196116B1/pl not_active IP Right Cessation
- 1999-09-20 CN CNB998114324A patent/CN1189446C/zh not_active Expired - Fee Related
- 1999-09-20 JP JP2000572184A patent/JP3786834B2/ja not_active Expired - Fee Related
- 1999-09-20 KR KR10-2001-7003977A patent/KR100479256B1/ko not_active Expired - Fee Related
- 1999-09-20 WO PCT/ES1999/000294 patent/WO2000018722A2/es not_active Ceased
- 1999-09-20 HU HU0103969A patent/HUP0103969A3/hu unknown
- 1999-09-20 SK SK386-2001A patent/SK284366B6/sk not_active IP Right Cessation
- 1999-09-20 BR BR9913989-8A patent/BR9913989A/pt not_active Application Discontinuation
- 1999-09-20 CZ CZ20010958A patent/CZ296901B6/cs not_active IP Right Cessation
2001
- 2001-03-08 IS IS5880A patent/IS2016B/is unknown
- 2001-03-08 NO NO20011197A patent/NO327780B1/no not_active IP Right Cessation
2008
- 2008-10-16 NO NO20084343A patent/NO20084343L/no not_active Application Discontinuation

Also Published As

Publication number	Publication date
ES2142771A1 (es)	2000-04-16
AU5983999A (en)	2000-04-17
ES2142771B1 (es)	2001-01-01
HUP0103969A2 (hu)	2002-05-29
CN1320114A (zh)	2001-10-31
BR9913989A (pt)	2001-06-19
WO2000018722A2 (es)	2000-04-06
ES2212672T3 (es)	2004-07-16
NZ511157A (en)	2002-12-20
ATE254596T1 (de)	2003-12-15
OA11660A (en)	2004-12-08
EA003397B1 (ru)	2003-04-24
KR100479256B1 (ko)	2005-03-30
CZ296901B6 (cs)	2006-07-12
SK3862001A3 (en)	2002-09-10
TR200100862T2 (tr)	2001-07-23
CA2344647C (en)	2005-07-05
US6388134B1 (en)	2002-05-14
JP3786834B2 (ja)	2006-06-14
IS5880A (is)	2001-03-08
PT1132373E (pt)	2004-03-31
IS2016B (is)	2005-06-15
CN1189446C (zh)	2005-02-16
CZ296902B6 (cs)	2006-07-12
NO327780B1 (no)	2009-09-21
AU756042B2 (en)	2003-01-02
PL348572A1 (en)	2002-06-03
DE69912984D1 (de)	2003-12-24
IL141991A (en)	2004-03-28
WO2000018722A3 (es)	2000-07-06
EA200100391A1 (ru)	2001-10-22
CA2344647A1 (en)	2000-04-06
EP1132373A2 (en)	2001-09-12
NO20011197D0 (no)	2001-03-08
JP2002525349A (ja)	2002-08-13
IL141991A0 (en)	2002-03-10
KR20010079948A (ko)	2001-08-22
CZ2001958A3 (cs)	2001-08-15
NO20011197L (no)	2001-03-28
HUP0103969A3 (en)	2003-05-28
PL196116B1 (pl)	2007-12-31
NO20084343L (no)	2001-03-28
EP1132373B1 (en)	2003-11-19

Legal Events

Date	Code	Title	Description
2011-06-06	MM4A	Patent lapsed due to non-payment of maintenance fees	Effective date: 20100920

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JP2023002679A (ja)	2023-01-10	チトクロームｐ４５０モノオキシゲナーゼの阻害剤およびそれに関わる中間体
EP2200983A1 (fr)	2010-06-30	Procede de preparation d'une piperidine disubstituee et intermediaires
CZ284256B6 (cs)	1998-10-14	Nový způsob výroby formoterolu a příbuzných sloučenin
SK3862001A3 (en)	2002-09-10	New derivatives of 6-(4-phenylbutoxy)hexylamine and process for producing salmeterol
JP4299677B2 (ja)	2009-07-22	コンブレタスタチンの製造方法
US5618968A (en)	1997-04-08	N-substituted derivatives of N-methyl-3-(p-trifluoromethylphenoxy)-3-phenylpropylamine and the procedure for their preparation
EP2666771A1 (en)	2013-11-27	Synthesis of Aminocyclopentanetriol Derivatives
WO2008155613A1 (en)	2008-12-24	An improved process for preparing purine derivative
WO2014154908A1 (en)	2014-10-02	Selective alkylation of cyclopentyl alcohols
FR2528422A1 (fr)	1983-12-16	Nouveaux derives du 1,2,3,4-tetrahydronaphtalene, procede pour leur preparation et composition pharmaceutique contenant ces derives
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SK284168B6 (sk)	2004-10-05	Alkoxyfuranónamínové deriváty, spôsob ich prípravy, ich použitie a medziprodukty na ich prípravu
SK29099A3 (en)	1999-08-06	Process for the preparation of fluoxetine
Pujol et al.	1996	Novel tricyclic spiropiperidines. Synthesis and adrenergic activity of spiro [1, 3-benzodioxolopiperidines] and spiro [1, 3-benzodioxanepiperidines]
PL182914B1 (pl)	2002-04-30	Sposób wytwarzania (-)-N-metylo-N-[4-(4-fenylo-4-acetyloaminopiperydyn-1-ylo)-2-(3,4-dichlorofenylo)butylo]benzamidu
HUP0104259A2 (en)	2002-08-28	A process for the synthesis of ritonavir
MXPA01003222A (en)	2002-06-05	New derivatives of 6-(4-phenylbutoxy)hexylamine and process for producing salmeterol
SK4732000A3 (en)	2001-03-12	Preparation of asymmetric cyclic ureas through a monoacylated diamine intermediate
JPH054949A (ja)	1993-01-14	光学活性シクロブチルアミン類の製造方法
EP0318036A2 (en)	1989-05-31	Phenoxypropyl derivatives