NO790397L - Piperazinderivater. - Google Patents
Piperazinderivater.Info
- Publication number
- NO790397L NO790397L NO790397A NO790397A NO790397L NO 790397 L NO790397 L NO 790397L NO 790397 A NO790397 A NO 790397A NO 790397 A NO790397 A NO 790397A NO 790397 L NO790397 L NO 790397L
- Authority
- NO
- Norway
- Prior art keywords
- denotes
- compound
- formula
- group
- solution
- Prior art date
Links
- 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 title description 2
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical class C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 146
- 239000000203 mixture Substances 0.000 claims description 122
- -1 2-hydroxy-3-iso-propylaminopropoxy Chemical group 0.000 claims description 50
- 238000000034 method Methods 0.000 claims description 38
- 239000001257 hydrogen Substances 0.000 claims description 32
- 229910052739 hydrogen Inorganic materials 0.000 claims description 32
- 150000003839 salts Chemical class 0.000 claims description 32
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
- 239000002253 acid Substances 0.000 claims description 26
- 125000000217 alkyl group Chemical group 0.000 claims description 24
- YZTJYBJCZXZGCT-UHFFFAOYSA-N phenylpiperazine Chemical class C1CNCCN1C1=CC=CC=C1 YZTJYBJCZXZGCT-UHFFFAOYSA-N 0.000 claims description 22
- 238000002360 preparation method Methods 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 19
- DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 claims description 18
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 18
- 150000001412 amines Chemical class 0.000 claims description 12
- 125000006239 protecting group Chemical group 0.000 claims description 10
- SWEJBCLKZFYKJU-QFIPXVFZSA-N (2s)-1-[4-[2-(4-phenylpiperazin-1-yl)ethoxy]phenoxy]-3-(propan-2-ylamino)propan-2-ol Chemical compound C1=CC(OC[C@@H](O)CNC(C)C)=CC=C1OCCN1CCN(C=2C=CC=CC=2)CC1 SWEJBCLKZFYKJU-QFIPXVFZSA-N 0.000 claims description 7
- 125000003545 alkoxy group Chemical group 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 6
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 5
- 239000002876 beta blocker Substances 0.000 claims description 4
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 4
- 239000003638 chemical reducing agent Substances 0.000 claims description 4
- 239000007858 starting material Substances 0.000 claims description 4
- XBDVEVUYNVAKJF-SANMLTNESA-N (2s)-1-[4-[6-(4-phenylpiperazin-1-yl)hexoxy]phenoxy]-3-(propan-2-ylamino)propan-2-ol Chemical compound C1=CC(OC[C@@H](O)CNC(C)C)=CC=C1OCCCCCCN1CCN(C=2C=CC=CC=2)CC1 XBDVEVUYNVAKJF-SANMLTNESA-N 0.000 claims description 3
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 3
- 230000003287 optical effect Effects 0.000 claims description 2
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims 3
- BVPWJMCABCPUQY-UHFFFAOYSA-N 4-amino-5-chloro-2-methoxy-N-[1-(phenylmethyl)-4-piperidinyl]benzamide Chemical compound COC1=CC(N)=C(Cl)C=C1C(=O)NC1CCN(CC=2C=CC=CC=2)CC1 BVPWJMCABCPUQY-UHFFFAOYSA-N 0.000 claims 1
- 235000009581 Balanites aegyptiaca Nutrition 0.000 claims 1
- 239000002552 dosage form Substances 0.000 claims 1
- 239000003814 drug Substances 0.000 claims 1
- 229940079593 drug Drugs 0.000 claims 1
- 238000004519 manufacturing process Methods 0.000 claims 1
- 239000002731 stomach secretion inhibitor Substances 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 318
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 279
- 239000000243 solution Substances 0.000 description 231
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 206
- HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 205
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Natural products CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 187
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 162
- 238000006243 chemical reaction Methods 0.000 description 135
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 121
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 115
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 110
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 90
- 239000007787 solid Substances 0.000 description 72
- 239000002904 solvent Substances 0.000 description 72
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 68
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 64
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 57
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 55
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 52
- 238000010992 reflux Methods 0.000 description 43
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 42
- 239000003921 oil Substances 0.000 description 42
- 235000019198 oils Nutrition 0.000 description 42
- 239000011541 reaction mixture Substances 0.000 description 42
- 238000002425 crystallisation Methods 0.000 description 35
- 230000008025 crystallization Effects 0.000 description 35
- 238000001914 filtration Methods 0.000 description 35
- 239000000463 material Substances 0.000 description 34
- 239000000047 product Substances 0.000 description 34
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 32
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 30
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 30
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 29
- 239000000538 analytical sample Substances 0.000 description 29
- 239000010410 layer Substances 0.000 description 29
- 229910000027 potassium carbonate Inorganic materials 0.000 description 29
- 229960001760 dimethyl sulfoxide Drugs 0.000 description 28
- 239000000284 extract Substances 0.000 description 28
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 26
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 24
- 239000013078 crystal Substances 0.000 description 24
- 229910052938 sodium sulfate Inorganic materials 0.000 description 24
- 235000011152 sodium sulphate Nutrition 0.000 description 24
- 239000002585 base Substances 0.000 description 23
- 239000012044 organic layer Substances 0.000 description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
- 239000000706 filtrate Substances 0.000 description 21
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 20
- 238000003756 stirring Methods 0.000 description 20
- 239000000376 reactant Substances 0.000 description 19
- 238000001953 recrystallisation Methods 0.000 description 19
- 239000003054 catalyst Substances 0.000 description 18
- 150000002118 epoxides Chemical class 0.000 description 18
- 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 17
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 17
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 16
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 15
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 15
- CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 15
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 14
- 150000001298 alcohols Chemical class 0.000 description 14
- 150000002170 ethers Chemical class 0.000 description 14
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 description 14
- 230000002829 reductive effect Effects 0.000 description 14
- 239000000523 sample Substances 0.000 description 14
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 13
- 229910052786 argon Inorganic materials 0.000 description 13
- 239000011976 maleic acid Substances 0.000 description 13
- 238000001704 evaporation Methods 0.000 description 12
- 230000008020 evaporation Effects 0.000 description 12
- 150000003944 halohydrins Chemical class 0.000 description 12
- 239000000543 intermediate Substances 0.000 description 12
- JJWLVOIRVHMVIS-UHFFFAOYSA-N isopropylamine Chemical compound CC(C)N JJWLVOIRVHMVIS-UHFFFAOYSA-N 0.000 description 12
- 239000000741 silica gel Substances 0.000 description 12
- 229910002027 silica gel Inorganic materials 0.000 description 12
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 12
- 235000017557 sodium bicarbonate Nutrition 0.000 description 12
- 150000008044 alkali metal hydroxides Chemical class 0.000 description 11
- 239000012258 stirred mixture Substances 0.000 description 11
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- 239000012043 crude product Substances 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- 238000010934 O-alkylation reaction Methods 0.000 description 9
- 150000001408 amides Chemical group 0.000 description 9
- 238000001816 cooling Methods 0.000 description 9
- 150000002148 esters Chemical class 0.000 description 9
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 9
- 229910000029 sodium carbonate Inorganic materials 0.000 description 9
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 8
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 8
- 238000009835 boiling Methods 0.000 description 8
- IJOOHPMOJXWVHK-UHFFFAOYSA-N chlorotrimethylsilane Chemical compound C[Si](C)(C)Cl IJOOHPMOJXWVHK-UHFFFAOYSA-N 0.000 description 8
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 8
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 8
- 238000007327 hydrogenolysis reaction Methods 0.000 description 8
- 239000005457 ice water Substances 0.000 description 8
- 239000012442 inert solvent Substances 0.000 description 8
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 8
- 239000002244 precipitate Substances 0.000 description 8
- 150000003512 tertiary amines Chemical class 0.000 description 8
- FBPFZTCFMRRESA-KVTDHHQDSA-N D-Mannitol Chemical compound OC[C@@H](O)[C@@H](O)[C@H](O)[C@H](O)CO FBPFZTCFMRRESA-KVTDHHQDSA-N 0.000 description 7
- JEDZLBFUGJTJGQ-UHFFFAOYSA-N [Na].COCCO[AlH]OCCOC Chemical compound [Na].COCCO[AlH]OCCOC JEDZLBFUGJTJGQ-UHFFFAOYSA-N 0.000 description 7
- 239000002168 alkylating agent Substances 0.000 description 7
- 229940100198 alkylating agent Drugs 0.000 description 7
- 229910052799 carbon Inorganic materials 0.000 description 7
- 229910052736 halogen Inorganic materials 0.000 description 7
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 7
- 150000003141 primary amines Chemical class 0.000 description 7
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 7
- NTIAVUBMOJPJPM-UHFFFAOYSA-N 1-(2-chloroethyl)-4-phenylpiperazine Chemical compound C1CN(CCCl)CCN1C1=CC=CC=C1 NTIAVUBMOJPJPM-UHFFFAOYSA-N 0.000 description 6
- PLIKAWJENQZMHA-UHFFFAOYSA-N 4-aminophenol Chemical compound NC1=CC=C(O)C=C1 PLIKAWJENQZMHA-UHFFFAOYSA-N 0.000 description 6
- CURLTUGMZLYLDI-UHFFFAOYSA-N Carbon dioxide Chemical compound O=C=O CURLTUGMZLYLDI-UHFFFAOYSA-N 0.000 description 6
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
- 239000012267 brine Substances 0.000 description 6
- 239000003153 chemical reaction reagent Substances 0.000 description 6
- 125000004122 cyclic group Chemical group 0.000 description 6
- 229910052500 inorganic mineral Inorganic materials 0.000 description 6
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 6
- 235000010755 mineral Nutrition 0.000 description 6
- 239000011707 mineral Substances 0.000 description 6
- 239000012419 sodium bis(2-methoxyethoxy)aluminum hydride Substances 0.000 description 6
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 6
- 210000001519 tissue Anatomy 0.000 description 6
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 6
- JWZZKOKVBUJMES-UHFFFAOYSA-N (+-)-Isoprenaline Chemical compound CC(C)NCC(O)C1=CC=C(O)C(O)=C1 JWZZKOKVBUJMES-UHFFFAOYSA-N 0.000 description 5
- DBVOADYMWPGUPF-UHFFFAOYSA-N 2-(4-prop-2-enoxyphenyl)acetic acid Chemical compound OC(=O)CC1=CC=C(OCC=C)C=C1 DBVOADYMWPGUPF-UHFFFAOYSA-N 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 5
- BRLQWZUYTZBJKN-UHFFFAOYSA-N Epichlorohydrin Chemical compound ClCC1CO1 BRLQWZUYTZBJKN-UHFFFAOYSA-N 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 5
- 239000005557 antagonist Substances 0.000 description 5
- 239000000010 aprotic solvent Substances 0.000 description 5
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 5
- 239000003610 charcoal Substances 0.000 description 5
- 239000012230 colorless oil Substances 0.000 description 5
- 239000006184 cosolvent Substances 0.000 description 5
- MHDVGSVTJDSBDK-UHFFFAOYSA-N dibenzyl ether Chemical compound C=1C=CC=CC=1COCC1=CC=CC=C1 MHDVGSVTJDSBDK-UHFFFAOYSA-N 0.000 description 5
- 230000000694 effects Effects 0.000 description 5
- 150000002367 halogens Chemical class 0.000 description 5
- 229940039009 isoproterenol Drugs 0.000 description 5
- 238000002156 mixing Methods 0.000 description 5
- 229910000510 noble metal Inorganic materials 0.000 description 5
- 230000035484 reaction time Effects 0.000 description 5
- 239000002002 slurry Substances 0.000 description 5
- 239000011734 sodium Substances 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- HDPNBNXLBDFELL-UHFFFAOYSA-N 1,1,1-trimethoxyethane Chemical compound COC(C)(OC)OC HDPNBNXLBDFELL-UHFFFAOYSA-N 0.000 description 4
- NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 4
- 239000005711 Benzoic acid Substances 0.000 description 4
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
- VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 4
- 239000012300 argon atmosphere Substances 0.000 description 4
- 235000010233 benzoic acid Nutrition 0.000 description 4
- 230000000903 blocking effect Effects 0.000 description 4
- 239000007795 chemical reaction product Substances 0.000 description 4
- 239000013058 crude material Substances 0.000 description 4
- 238000010828 elution Methods 0.000 description 4
- RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 4
- 239000012467 final product Substances 0.000 description 4
- 239000012458 free base Substances 0.000 description 4
- 210000002837 heart atrium Anatomy 0.000 description 4
- 125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 4
- 150000004678 hydrides Chemical class 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- 238000011065 in-situ storage Methods 0.000 description 4
- 235000010355 mannitol Nutrition 0.000 description 4
- ZGEGCLOFRBLKSE-UHFFFAOYSA-N methylene hexane Natural products CCCCCC=C ZGEGCLOFRBLKSE-UHFFFAOYSA-N 0.000 description 4
- VYQNWZOUAUKGHI-UHFFFAOYSA-N monobenzone Chemical compound C1=CC(O)=CC=C1OCC1=CC=CC=C1 VYQNWZOUAUKGHI-UHFFFAOYSA-N 0.000 description 4
- 229910052763 palladium Inorganic materials 0.000 description 4
- LCPDWSOZIOUXRV-UHFFFAOYSA-N phenoxyacetic acid Chemical compound OC(=O)COC1=CC=CC=C1 LCPDWSOZIOUXRV-UHFFFAOYSA-N 0.000 description 4
- 229910052697 platinum Inorganic materials 0.000 description 4
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 238000006894 reductive elimination reaction Methods 0.000 description 4
- 229910052708 sodium Inorganic materials 0.000 description 4
- GETQZCLCWQTVFV-UHFFFAOYSA-N trimethylamine Chemical compound CN(C)C GETQZCLCWQTVFV-UHFFFAOYSA-N 0.000 description 4
- 239000005051 trimethylchlorosilane Substances 0.000 description 4
- QNYBOILAKBSWFG-SNVBAGLBSA-N (2s)-2-(phenylmethoxymethyl)oxirane Chemical compound C([C@H]1OC1)OCC1=CC=CC=C1 QNYBOILAKBSWFG-SNVBAGLBSA-N 0.000 description 3
- UCTWMZQNUQWSLP-VIFPVBQESA-N (R)-adrenaline Chemical compound CNC[C@H](O)C1=CC=C(O)C(O)=C1 UCTWMZQNUQWSLP-VIFPVBQESA-N 0.000 description 3
- 229930182837 (R)-adrenaline Natural products 0.000 description 3
- SLSUCDCLLBIAHT-OAQYLSRUSA-N 1-[2-[4-[[(2s)-oxiran-2-yl]methoxy]phenoxy]ethyl]-4-phenylpiperazine Chemical compound C=1C=C(OC[C@H]2OC2)C=CC=1OCCN(CC1)CCN1C1=CC=CC=C1 SLSUCDCLLBIAHT-OAQYLSRUSA-N 0.000 description 3
- NBRLVMZEWJJYEK-UHFFFAOYSA-N 1-phenyl-4-[2-(4-phenylmethoxyphenoxy)ethyl]piperazine Chemical compound C=1C=C(OCC=2C=CC=CC=2)C=CC=1OCCN(CC1)CCN1C1=CC=CC=C1 NBRLVMZEWJJYEK-UHFFFAOYSA-N 0.000 description 3
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/16—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms
- C07D295/18—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms acylated on ring nitrogen atoms by radicals derived from carboxylic acids, or sulfur or nitrogen analogues thereof
- C07D295/182—Radicals derived from carboxylic acids
- C07D295/185—Radicals derived from carboxylic acids from aliphatic carboxylic acids
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
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- C07D317/00—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms
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- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
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- C07D317/08—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3
- C07D317/10—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings
- C07D317/32—Heterocyclic compounds containing five-membered rings having two oxygen atoms as the only ring hetero atoms having the hetero atoms in positions 1 and 3 not condensed with other rings 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
- C07D317/34—Oxygen atoms
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- Chemical & Material Sciences (AREA)
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- Cardiology (AREA)
- Biomedical Technology (AREA)
- Neurology (AREA)
- Neurosurgery (AREA)
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Applications Claiming Priority (1)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
US05/875,966 US4202978A (en) | 1978-02-08 | 1978-02-08 | (S)-1-[2-(4-(2-Hydroxy-s-(1-alkylaminopropoxy)phenylalkyl]-4-phenylpiperazines |
Publications (1)
Publication Number | Publication Date |
---|---|
NO790397L true NO790397L (no) | 1979-08-09 |
Family
ID=25366682
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
NO790397A NO790397L (no) | 1978-02-08 | 1979-02-07 | Piperazinderivater. |
Country Status (22)
Country | Link |
---|---|
US (1) | US4202978A (fi) |
EP (1) | EP0005142A1 (fi) |
JP (1) | JPS54117488A (fi) |
AU (1) | AU4402979A (fi) |
BR (1) | BR7900752A (fi) |
CU (1) | CU35033A (fi) |
DE (1) | DE2904799A1 (fi) |
DK (1) | DK50779A (fi) |
ES (4) | ES8306125A1 (fi) |
FI (1) | FI790381A (fi) |
FR (2) | FR2416888A1 (fi) |
GB (1) | GB2014145A (fi) |
GR (1) | GR72416B (fi) |
IE (1) | IE790233L (fi) |
IL (1) | IL56600A0 (fi) |
LU (1) | LU80887A1 (fi) |
MC (1) | MC1252A1 (fi) |
NL (1) | NL7900975A (fi) |
NO (1) | NO790397L (fi) |
PT (1) | PT69194A (fi) |
SE (1) | SE7901099L (fi) |
ZA (1) | ZA79397B (fi) |
Families Citing this family (27)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US3857588A (en) * | 1973-02-05 | 1974-12-31 | H Curtin | Pipe coupling |
US4281189A (en) * | 1979-09-06 | 1981-07-28 | Hoffmann-La Roche Inc. | Sulfonamide intermediates for adrenergic blocking agents |
US4301300A (en) * | 1979-09-06 | 1981-11-17 | Hoffmann-La Roche Inc. | Sulfonamide intermediates for adrenergic blocking agents |
JPS6224254Y2 (fi) * | 1979-09-17 | 1987-06-20 | ||
DE2937595A1 (de) * | 1979-09-18 | 1981-04-02 | Bayer Ag, 5090 Leverkusen | Verfahren zur herstellung von 1-azolyl-1-phenoxy-alkan-2-onen |
US4387103A (en) * | 1980-11-28 | 1983-06-07 | American Hospital Supply Corporation | Method for treatment or prophylaxis of cardiac disorders |
CA1262128A (en) * | 1981-08-27 | 1989-10-03 | Christian N. Hubschwerlen | .beta.-lactams |
GB8303946D0 (en) * | 1983-02-12 | 1983-03-16 | Recordati Chem Pharm | Antihypertensive n-piperazinylalkanoylanilides |
DE3319027A1 (de) * | 1983-05-26 | 1984-11-29 | Boehringer Mannheim Gmbh, 6800 Mannheim | Verfahren zur herstellung von optisch aktiven carbazol-derivaten, neue r- und s-carbazol-derivate, sowie arzneimittel, die diese verbindungen enthalten |
FR2585355B2 (fr) * | 1985-07-26 | 1988-11-25 | Cortial | Nouvelles n1-((aminoalcoxy)-4 isopropyl-5 methyl-2 phenoxy)-2 ethyl n4-phenyl piperazines, leur methode de preparation et leur application therapeutique |
EP0179009A1 (fr) * | 1984-09-19 | 1986-04-23 | Cortial S.A. | Nouvelles n1-(aminoalcoxy)-4 isopropyl-5 phénoxy)-2 éthyl n4-phényl pipérazines, leur méthode de préparation et leur application thérapeutique |
FR2570376B1 (fr) * | 1984-09-19 | 1987-09-25 | Cortial | Nouveaux (isopropyl-5 (((methoxy-2 phenyl) piperazinyl)-2 ethoxy)-4 methyl-2 phenoxy)-1 alkylamino-3 propanols-2, leur methode de preparation et leur application therapeutique |
JPS63502585A (ja) * | 1985-12-04 | 1988-09-29 | ザ デュポン メルク ファーマシュウティカル カンパニー | アリルオキシプロパノ−ルアミン類及びアリルエタノ−ルアミン類の合成法 |
US4990668A (en) * | 1985-12-04 | 1991-02-05 | E. I. Du Pont De Nemours And Company | Optically active aryloxypropanolamines and arylethanolamines |
DE3715482A1 (de) * | 1987-05-08 | 1988-11-24 | Bayer Ag | Schaedlingsbekaempfungsmittel auf basis von substituierten aminomethylheterocyclen |
US5047540A (en) * | 1987-12-17 | 1991-09-10 | Shionogi & Co., Ltd. | Lipid derivatives |
US5179124A (en) * | 1988-01-25 | 1993-01-12 | University Of Iowa Research Foundation | Anti-inflammatory for use in external and internal eye inflammations |
US4968718A (en) * | 1988-01-25 | 1990-11-06 | University Of Iowa Research Foundation | Topically effective, nonsteroidal drug for use in external and internal eye inflammations |
JPH05255089A (ja) * | 1991-12-18 | 1993-10-05 | Sanwa Kagaku Kenkyusho Co Ltd | 抗ウイルス剤 |
US5380755A (en) * | 1992-07-24 | 1995-01-10 | The Du Pont Merck Pharmaceutical Company | Alkyl and alkylbenzyl ethers of substituted hydroquinones |
US5661163A (en) | 1995-06-07 | 1997-08-26 | Merck & Co., Inc. | Alpha-1a adrenergic receptor antagonists |
ZA98900B (en) * | 1997-02-07 | 1998-08-03 | Shell Int Research | Process for the manufacture of epoxy compounds |
WO2004002973A1 (ja) * | 2002-06-28 | 2004-01-08 | Kaneka Corporation | 光学活性1−置換アミノー2,3−エポキシプロパンの製造方法並びにその合成中間体およびそれらの製造方法 |
JP4953754B2 (ja) * | 2006-10-19 | 2012-06-13 | 株式会社トクヤマ | ハロヒドリン化合物 |
CA3001857A1 (en) * | 2015-10-14 | 2017-04-20 | Aquinnah Pharmaceuticals, Inc. | Compounds, compositions and methods of use against stress granules |
PT117440B (pt) | 2021-09-03 | 2024-04-26 | Hovione Farm S A | Processo para a preparação de aminas cíclicas cloroaquilo substituídas |
AU2023242443A1 (en) * | 2022-03-28 | 2024-08-29 | F. Hoffmann-La Roche Ag | Synthesis of isomerically pure polyol-based phosphoramidites |
Family Cites Families (7)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
FR1349636A (fr) * | 1962-02-26 | 1964-01-17 | Soc Ind Fab Antibiotiques Sifa | Nouveaux dérivés de la pipérazine, et procédé de préparation |
GB1058822A (en) * | 1963-07-30 | 1967-02-15 | Ici Ltd | 3-amino-2-hydroxypropoxy heterocyclic derivatives |
US3524851A (en) * | 1966-10-21 | 1970-08-18 | Merck & Co Inc | 1-phenoxy-3-morpholino alkylamino-2-propanols |
GB1185045A (en) * | 1966-11-03 | 1970-03-18 | Ici Ltd | Amine Derivatives |
DE1670200A1 (de) * | 1967-03-22 | 1972-03-02 | Byk Gulden Lomberg Chem Fab | Neue arylsubstituierte Piperazinylcarbonsaeureanilide und Verfahren zu deren Herstellung |
CA956632A (en) * | 1969-05-16 | 1974-10-22 | Yoshitomi Pharmaceutical Industries | Phenoxy-aminopropanol derivatives |
CH585693A5 (fi) * | 1974-02-08 | 1977-03-15 | Ciba Geigy Ag |
-
1978
- 1978-02-08 US US05/875,966 patent/US4202978A/en not_active Expired - Lifetime
-
1979
- 1979-01-30 ZA ZA79397A patent/ZA79397B/xx unknown
- 1979-02-02 FR FR7902733A patent/FR2416888A1/fr active Pending
- 1979-02-05 CU CU7935033A patent/CU35033A/es unknown
- 1979-02-06 LU LU80887A patent/LU80887A1/de unknown
- 1979-02-06 IL IL56600A patent/IL56600A0/xx unknown
- 1979-02-06 FI FI790381A patent/FI790381A/fi unknown
- 1979-02-06 MC MC791361A patent/MC1252A1/xx unknown
- 1979-02-06 JP JP1191279A patent/JPS54117488A/ja active Pending
- 1979-02-06 GR GR58277A patent/GR72416B/el unknown
- 1979-02-07 AU AU44029/79A patent/AU4402979A/en not_active Abandoned
- 1979-02-07 NO NO790397A patent/NO790397L/no unknown
- 1979-02-07 BR BR7900752A patent/BR7900752A/pt unknown
- 1979-02-07 IE IE790233A patent/IE790233L/xx unknown
- 1979-02-07 NL NL7900975A patent/NL7900975A/xx not_active Application Discontinuation
- 1979-02-07 ES ES477509A patent/ES8306125A1/es not_active Expired
- 1979-02-07 DK DK50779A patent/DK50779A/da not_active Application Discontinuation
- 1979-02-07 GB GB7904336A patent/GB2014145A/en not_active Withdrawn
- 1979-02-07 PT PT7969194A patent/PT69194A/pt unknown
- 1979-02-07 SE SE7901099A patent/SE7901099L/xx not_active Application Discontinuation
- 1979-02-08 DE DE19792904799 patent/DE2904799A1/de not_active Withdrawn
- 1979-02-08 EP EP79100363A patent/EP0005142A1/de not_active Withdrawn
- 1979-09-04 FR FR7922072A patent/FR2490645A1/fr active Pending
- 1979-10-23 ES ES485272A patent/ES485272A1/es not_active Expired
- 1979-10-23 ES ES485274A patent/ES485274A1/es not_active Expired
- 1979-10-23 ES ES485273A patent/ES485273A1/es not_active Expired
Also Published As
Publication number | Publication date |
---|---|
ES485272A1 (es) | 1980-07-01 |
IL56600A0 (en) | 1979-10-31 |
MC1252A1 (fr) | 1980-01-14 |
PT69194A (en) | 1979-03-01 |
NL7900975A (nl) | 1979-08-10 |
GB2014145A (en) | 1979-08-22 |
CU35033A (en) | 1981-12-04 |
LU80887A1 (de) | 1980-09-24 |
US4202978A (en) | 1980-05-13 |
ES477509A0 (es) | 1982-09-01 |
ES8306125A1 (es) | 1982-09-01 |
SE7901099L (sv) | 1979-10-08 |
ZA79397B (en) | 1980-02-27 |
ES485274A1 (es) | 1980-07-16 |
DK50779A (da) | 1979-09-19 |
AU4402979A (en) | 1979-08-16 |
FR2416888A1 (fr) | 1979-09-07 |
IE790233L (en) | 1979-08-08 |
GR72416B (fi) | 1983-11-03 |
BR7900752A (pt) | 1979-09-04 |
DE2904799A1 (de) | 1979-08-09 |
FI790381A (fi) | 1979-08-09 |
JPS54117488A (en) | 1979-09-12 |
FR2490645A1 (fr) | 1982-03-26 |
ES485273A1 (es) | 1980-07-01 |
EP0005142A1 (de) | 1979-11-14 |
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