DE1964510A1 - 1-Substituierte-3-substituierte Phenoxypyrrolidine und Verfahren zu deren Herstellung - Google Patents
1-Substituierte-3-substituierte Phenoxypyrrolidine und Verfahren zu deren HerstellungInfo
- Publication number
- DE1964510A1 DE1964510A1 DE19691964510 DE1964510A DE1964510A1 DE 1964510 A1 DE1964510 A1 DE 1964510A1 DE 19691964510 DE19691964510 DE 19691964510 DE 1964510 A DE1964510 A DE 1964510A DE 1964510 A1 DE1964510 A1 DE 1964510A1
- Authority
- DE
- Germany
- Prior art keywords
- substituted
- carbamoyl
- phenoxypyrrolidine
- benzyl
- methyl
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- -1 1-substituted-3-substituted phenoxypyrrolidines Chemical class 0.000 title claims description 33
- 238000000034 method Methods 0.000 title claims description 18
- 238000002360 preparation method Methods 0.000 title claims description 11
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 11
- 150000003839 salts Chemical class 0.000 claims description 11
- 239000002253 acid Substances 0.000 claims description 10
- AUSRRRUBMHIEJD-UHFFFAOYSA-N 1-phenoxypyrrolidine Chemical class C1CCCN1OC1=CC=CC=C1 AUSRRRUBMHIEJD-UHFFFAOYSA-N 0.000 claims description 6
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 5
- 238000006243 chemical reaction Methods 0.000 claims description 5
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
- SKZKKFZAGNVIMN-UHFFFAOYSA-N Salicilamide Chemical compound NC(=O)C1=CC=CC=C1O SKZKKFZAGNVIMN-UHFFFAOYSA-N 0.000 claims description 4
- 125000000217 alkyl group Chemical group 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 4
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 3
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 3
- ODZPKZBBUMBTMG-UHFFFAOYSA-N sodium amide Chemical compound [NH2-].[Na+] ODZPKZBBUMBTMG-UHFFFAOYSA-N 0.000 claims description 3
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 2
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 2
- 125000004202 aminomethyl group Chemical group [H]N([H])C([H])([H])* 0.000 claims description 2
- 125000001951 carbamoylamino group Chemical group C(N)(=O)N* 0.000 claims description 2
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 2
- FLVFPAIGVBQGET-UHFFFAOYSA-N 1-methylpyrrolidin-3-ol Chemical compound CN1CCC(O)C1 FLVFPAIGVBQGET-UHFFFAOYSA-N 0.000 claims 1
- 230000010933 acylation Effects 0.000 claims 1
- 238000005917 acylation reaction Methods 0.000 claims 1
- 150000001412 amines Chemical class 0.000 claims 1
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims 1
- 159000000000 sodium salts Chemical class 0.000 claims 1
- RWRDLPDLKQPQOW-UHFFFAOYSA-N Pyrrolidine Chemical compound C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 43
- 150000001875 compounds Chemical class 0.000 description 31
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 18
- 239000000243 solution Substances 0.000 description 16
- YXFVVABEGXRONW-UHFFFAOYSA-N toluene Substances CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 16
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 16
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 15
- 239000000203 mixture Substances 0.000 description 15
- 239000004480 active ingredient Substances 0.000 description 12
- 238000004458 analytical method Methods 0.000 description 9
- 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 description 8
- 239000002775 capsule Substances 0.000 description 7
- 238000010586 diagram Methods 0.000 description 7
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 6
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
- 239000008187 granular material Substances 0.000 description 6
- 239000008101 lactose Substances 0.000 description 6
- 239000000155 melt Substances 0.000 description 6
- 238000002844 melting Methods 0.000 description 5
- 230000008018 melting Effects 0.000 description 5
- 239000002904 solvent Substances 0.000 description 5
- 229920002261 Corn starch Polymers 0.000 description 4
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 4
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 4
- WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
- CJZGTCYPCWQAJB-UHFFFAOYSA-L calcium stearate Chemical compound [Ca+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O CJZGTCYPCWQAJB-UHFFFAOYSA-L 0.000 description 4
- 239000008116 calcium stearate Substances 0.000 description 4
- 235000013539 calcium stearate Nutrition 0.000 description 4
- 239000008120 corn starch Substances 0.000 description 4
- 229940099112 cornstarch Drugs 0.000 description 4
- HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 4
- 239000003921 oil Substances 0.000 description 4
- 235000019198 oils Nutrition 0.000 description 4
- 239000011541 reaction mixture Substances 0.000 description 4
- 239000000126 substance Substances 0.000 description 4
- SKHPQIQATRHESG-UHFFFAOYSA-N 3-phenoxypyrrolidine Chemical class C1NCCC1OC1=CC=CC=C1 SKHPQIQATRHESG-UHFFFAOYSA-N 0.000 description 3
- 235000019739 Dicalciumphosphate Nutrition 0.000 description 3
- MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 125000003118 aryl group Chemical group 0.000 description 3
- 238000009835 boiling Methods 0.000 description 3
- 239000001506 calcium phosphate Substances 0.000 description 3
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 3
- NEFBYIFKOOEVPA-UHFFFAOYSA-K dicalcium phosphate Chemical compound [Ca+2].[Ca+2].[O-]P([O-])([O-])=O NEFBYIFKOOEVPA-UHFFFAOYSA-K 0.000 description 3
- 229940038472 dicalcium phosphate Drugs 0.000 description 3
- 229910000390 dicalcium phosphate Inorganic materials 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000010410 layer Substances 0.000 description 3
- 238000007911 parenteral administration Methods 0.000 description 3
- 229960000581 salicylamide Drugs 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 3
- 239000000725 suspension Substances 0.000 description 3
- DNXIKVLOVZVMQF-UHFFFAOYSA-N (3beta,16beta,17alpha,18beta,20alpha)-17-hydroxy-11-methoxy-18-[(3,4,5-trimethoxybenzoyl)oxy]-yohimban-16-carboxylic acid, methyl ester Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(C(=O)OC)C(O)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 DNXIKVLOVZVMQF-UHFFFAOYSA-N 0.000 description 2
- CDAWCLOXVUBKRW-UHFFFAOYSA-N 2-aminophenol Chemical compound NC1=CC=CC=C1O CDAWCLOXVUBKRW-UHFFFAOYSA-N 0.000 description 2
- HDECRAPHCDXMIJ-UHFFFAOYSA-N 2-methylbenzenesulfonyl chloride Chemical compound CC1=CC=CC=C1S(Cl)(=O)=O HDECRAPHCDXMIJ-UHFFFAOYSA-N 0.000 description 2
- HCYAFALTSJYZDH-UHFFFAOYSA-N Desimpramine Chemical compound C1CC2=CC=CC=C2N(CCCNC)C2=CC=CC=C21 HCYAFALTSJYZDH-UHFFFAOYSA-N 0.000 description 2
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 2
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N Phenol Chemical compound OC1=CC=CC=C1 ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 description 2
- LCQMZZCPPSWADO-UHFFFAOYSA-N Reserpilin Natural products COC(=O)C1COCC2CN3CCc4c([nH]c5cc(OC)c(OC)cc45)C3CC12 LCQMZZCPPSWADO-UHFFFAOYSA-N 0.000 description 2
- QEVHRUUCFGRFIF-SFWBKIHZSA-N Reserpine Natural products O=C(OC)[C@@H]1[C@H](OC)[C@H](OC(=O)c2cc(OC)c(OC)c(OC)c2)C[C@H]2[C@@H]1C[C@H]1N(C2)CCc2c3c([nH]c12)cc(OC)cc3 QEVHRUUCFGRFIF-SFWBKIHZSA-N 0.000 description 2
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 2
- 229920002472 Starch Polymers 0.000 description 2
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric Acid Chemical compound [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
- 230000002378 acidificating effect Effects 0.000 description 2
- 125000005115 alkyl carbamoyl group Chemical group 0.000 description 2
- OSASVXMJTNOKOY-UHFFFAOYSA-N chlorobutanol Chemical compound CC(C)(O)C(Cl)(Cl)Cl OSASVXMJTNOKOY-UHFFFAOYSA-N 0.000 description 2
- 230000000052 comparative effect Effects 0.000 description 2
- 239000002274 desiccant Substances 0.000 description 2
- 229960003914 desipramine Drugs 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 238000009472 formulation Methods 0.000 description 2
- 238000007327 hydrogenolysis reaction Methods 0.000 description 2
- 239000004615 ingredient Substances 0.000 description 2
- 229910052500 inorganic mineral Inorganic materials 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 235000019359 magnesium stearate Nutrition 0.000 description 2
- 238000004519 manufacturing process Methods 0.000 description 2
- 239000000463 material Substances 0.000 description 2
- 239000011707 mineral Substances 0.000 description 2
- 231100000252 nontoxic Toxicity 0.000 description 2
- 230000003000 nontoxic effect Effects 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- 235000005985 organic acids Nutrition 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- BJOIZNZVOZKDIG-MDEJGZGSSA-N reserpine Chemical compound O([C@H]1[C@@H]([C@H]([C@H]2C[C@@H]3C4=C([C]5C=CC(OC)=CC5=N4)CCN3C[C@H]2C1)C(=O)OC)OC)C(=O)C1=CC(OC)=C(OC)C(OC)=C1 BJOIZNZVOZKDIG-MDEJGZGSSA-N 0.000 description 2
- 229960003147 reserpine Drugs 0.000 description 2
- MDMGHDFNKNZPAU-UHFFFAOYSA-N roserpine Natural products C1C2CN3CCC(C4=CC=C(OC)C=C4N4)=C4C3CC2C(OC(C)=O)C(OC)C1OC(=O)C1=CC(OC)=C(OC)C(OC)=C1 MDMGHDFNKNZPAU-UHFFFAOYSA-N 0.000 description 2
- 229910052938 sodium sulfate Inorganic materials 0.000 description 2
- 235000011152 sodium sulphate Nutrition 0.000 description 2
- 235000019698 starch Nutrition 0.000 description 2
- 238000007920 subcutaneous administration Methods 0.000 description 2
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 2
- HMGDLYUTYLPXDR-UHFFFAOYSA-N 1-benzyl-3-phenoxypyrrolidine Chemical class C=1C=CC=CC=1CN(C1)CCC1OC1=CC=CC=C1 HMGDLYUTYLPXDR-UHFFFAOYSA-N 0.000 description 1
- CWLUFVAFWWNXJZ-UHFFFAOYSA-N 1-hydroxypyrrolidine Chemical class ON1CCCC1 CWLUFVAFWWNXJZ-UHFFFAOYSA-N 0.000 description 1
- QTFVFOQCSACSKY-UHFFFAOYSA-N 1-methyl-3-phenoxypyrrolidine Chemical class C1N(C)CCC1OC1=CC=CC=C1 QTFVFOQCSACSKY-UHFFFAOYSA-N 0.000 description 1
- BOPZLFFVWLMGAT-UHFFFAOYSA-N 2-(1-benzylpyrrolidin-3-yl)oxybenzamide Chemical compound NC(=O)C1=CC=CC=C1OC1CN(CC=2C=CC=CC=2)CC1 BOPZLFFVWLMGAT-UHFFFAOYSA-N 0.000 description 1
- BUHYMJLFRZAFBF-UHFFFAOYSA-N 3,4,5-trimethoxybenzoyl chloride Chemical compound COC1=CC(C(Cl)=O)=CC(OC)=C1OC BUHYMJLFRZAFBF-UHFFFAOYSA-N 0.000 description 1
- QXSAKPUBHTZHKW-UHFFFAOYSA-N 4-hydroxybenzamide Chemical compound NC(=O)C1=CC=C(O)C=C1 QXSAKPUBHTZHKW-UHFFFAOYSA-N 0.000 description 1
- CKDWPUIZGOQOOM-UHFFFAOYSA-N Carbamyl chloride Chemical compound NC(Cl)=O CKDWPUIZGOQOOM-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 108010010803 Gelatin Proteins 0.000 description 1
- 241000883306 Huso huso Species 0.000 description 1
- 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 1
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- 241000699666 Mus <mouse, genus> Species 0.000 description 1
- 101100203658 Mus musculus Spag1 gene Proteins 0.000 description 1
- 241000699670 Mus sp. Species 0.000 description 1
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 1
- 235000019483 Peanut oil Nutrition 0.000 description 1
- FCLZCOCSZQNREK-UHFFFAOYSA-N Pyrrolidine, hydrochloride Chemical compound Cl.C1CCNC1 FCLZCOCSZQNREK-UHFFFAOYSA-N 0.000 description 1
- 244000061456 Solanum tuberosum Species 0.000 description 1
- 235000002595 Solanum tuberosum Nutrition 0.000 description 1
- 150000007513 acids Chemical class 0.000 description 1
- 125000004390 alkyl sulfonyl group Chemical group 0.000 description 1
- 125000003277 amino group Chemical group 0.000 description 1
- 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- 230000003042 antagnostic effect Effects 0.000 description 1
- 239000000935 antidepressant agent Substances 0.000 description 1
- 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
- SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 1
- 229940077388 benzenesulfonate Drugs 0.000 description 1
- CSKNSYBAZOQPLR-UHFFFAOYSA-N benzenesulfonyl chloride Chemical compound ClS(=O)(=O)C1=CC=CC=C1 CSKNSYBAZOQPLR-UHFFFAOYSA-N 0.000 description 1
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 description 1
- 239000003054 catalyst Substances 0.000 description 1
- 239000000460 chlorine Substances 0.000 description 1
- 229910052801 chlorine Inorganic materials 0.000 description 1
- 229960004926 chlorobutanol Drugs 0.000 description 1
- 235000015165 citric acid Nutrition 0.000 description 1
- 238000001816 cooling Methods 0.000 description 1
- 230000007423 decrease Effects 0.000 description 1
- 210000003298 dental enamel Anatomy 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 238000001704 evaporation Methods 0.000 description 1
- 230000008020 evaporation Effects 0.000 description 1
- 239000000284 extract Substances 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 229920000159 gelatin Polymers 0.000 description 1
- 239000008273 gelatin Substances 0.000 description 1
- 235000019322 gelatine Nutrition 0.000 description 1
- 235000011852 gelatine desserts Nutrition 0.000 description 1
- 238000007429 general method Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 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 1
- 230000002631 hypothermal effect Effects 0.000 description 1
- 238000007918 intramuscular administration Methods 0.000 description 1
- 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 229910052751 metal Chemical group 0.000 description 1
- 239000002184 metal Chemical group 0.000 description 1
- 125000002911 monocyclic heterocycle group Chemical group 0.000 description 1
- 125000002347 octyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 210000000056 organ Anatomy 0.000 description 1
- 239000012044 organic layer Substances 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- SOWBFZRMHSNYGE-UHFFFAOYSA-N oxamic acid Chemical class NC(=O)C(O)=O SOWBFZRMHSNYGE-UHFFFAOYSA-N 0.000 description 1
- 239000000312 peanut oil Substances 0.000 description 1
- 239000000546 pharmaceutical excipient Substances 0.000 description 1
- 230000000144 pharmacologic effect Effects 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 description 1
- 235000013855 polyvinylpyrrolidone Nutrition 0.000 description 1
- 229920000036 polyvinylpyrrolidone Polymers 0.000 description 1
- 229920001592 potato starch Polymers 0.000 description 1
- 239000002243 precursor Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 125000000467 secondary amino group Chemical group [H]N([*:1])[*:2] 0.000 description 1
- 239000000377 silicon dioxide Substances 0.000 description 1
- 239000002002 slurry Substances 0.000 description 1
- 239000011734 sodium Substances 0.000 description 1
- 229910052708 sodium Inorganic materials 0.000 description 1
- IUUWHXKQKONFCC-UHFFFAOYSA-M sodium (2-hydroxybenzoyl)azanide Chemical compound [Na+].C(C=1C(O)=CC=CC=1)(=O)[NH-] IUUWHXKQKONFCC-UHFFFAOYSA-M 0.000 description 1
- KKCBUQHMOMHUOY-UHFFFAOYSA-N sodium oxide Chemical compound [O-2].[Na+].[Na+] KKCBUQHMOMHUOY-UHFFFAOYSA-N 0.000 description 1
- 229910001948 sodium oxide Inorganic materials 0.000 description 1
- 239000007787 solid Substances 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 239000008174 sterile solution Substances 0.000 description 1
- 150000003871 sulfonates Chemical class 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid group Chemical class S(O)(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 239000007916 tablet composition Substances 0.000 description 1
- 239000000454 talc Substances 0.000 description 1
- 229910052623 talc Inorganic materials 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- 125000001302 tertiary amino group Chemical group 0.000 description 1
- 239000008215 water for injection Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D207/00—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D207/02—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D207/04—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members
- C07D207/10—Heterocyclic compounds containing five-membered rings not condensed with other rings, with one nitrogen atom as the only ring hetero atom with only hydrogen or carbon atoms directly attached to the ring nitrogen atom having no double bonds between ring members or between ring members and non-ring members 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
- C07D207/12—Oxygen or sulfur atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US78639568A | 1968-12-23 | 1968-12-23 |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE1964510A1 true DE1964510A1 (de) | 1970-07-09 |
Family
ID=25138456
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19691964510 Pending DE1964510A1 (de) | 1968-12-23 | 1969-12-23 | 1-Substituierte-3-substituierte Phenoxypyrrolidine und Verfahren zu deren Herstellung |
Country Status (7)
| Country | Link |
|---|---|
| US (1) | US3577415A (enExample) |
| BR (1) | BR6915184D0 (enExample) |
| CA (1) | CA931572A (enExample) |
| CH (1) | CH556335A (enExample) |
| DE (1) | DE1964510A1 (enExample) |
| FR (1) | FR2026923B1 (enExample) |
| GB (1) | GB1280020A (enExample) |
Cited By (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2757766A1 (de) * | 1976-12-28 | 1978-06-29 | Robins Co Inc A H | 1-substituierte-3-aminoaethoxypyrrolidine, ihre herstellung und verwendung als blutdrucksenkendes mittel |
| EP0147909A1 (en) * | 1983-12-05 | 1985-07-10 | A.H. Robins Company, Incorporated | Aryloxy-N-(aminoalkyl)-1-pyrrolidine and piperidine carboxamides and carbothioamides having antiarrhythmic activity |
| EP0338331A1 (de) * | 1988-04-19 | 1989-10-25 | Bayer Ag | 1,3-Disubstituierte Pyrrolidine |
| EP0107930B1 (en) * | 1982-09-30 | 1990-11-28 | A.H. ROBINS COMPANY, INCORPORATED (a Delaware corporation) | Fused aromatic oxazepinones and sulphur analogues thereof and their preparation and use in counteracting histamine |
| US5274097A (en) * | 1988-04-19 | 1993-12-28 | Bayer Aktiengesellschaft | 1,3-disubstituted pyrrolidines |
| WO2010059393A1 (en) * | 2008-10-30 | 2010-05-27 | Janssen Pharmaceutica Nv | Serotonin receptor modulators |
| US8575364B2 (en) | 2008-10-30 | 2013-11-05 | Janssen Pharmaceutica Nv | Modulators of serotonin receptor |
| AU2010335277B2 (en) * | 2009-12-22 | 2016-07-07 | F. Hoffmann-La Roche Ag | Substituted benzamide derivatives |
| US10508107B2 (en) | 2016-03-17 | 2019-12-17 | Hoffmann-La Roche Inc. | Morpholine derivative |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2834114A1 (de) * | 1978-08-01 | 1980-02-14 | Schering Ag | Polyalkoxyphenylpyrrolidone iii, verfahren zu ihrer herstellung und ihre verwendung |
| MX6634E (es) * | 1979-01-09 | 1985-09-12 | Robins Co Inc A H | Procedimiento para preparar el isomero trans de 3-ariloxi-4-hidroxipirrolidinas |
| US4251541A (en) * | 1979-01-09 | 1981-02-17 | A. H. Robins Company, Inc. | 1-Substituted-3-arylthio-4-hydroxypyrrolidines |
| US4727152A (en) * | 1982-09-30 | 1988-02-23 | A. H. Robins Company, Inc. | Intermediates useful in the preparation of fused aromatic oxazepinones, thiazepinones, diazepinones and sulfur analogs thereof |
| IE62338B1 (en) * | 1988-06-22 | 1995-01-25 | Kanegafuchi Chemical Ind | Process for preparing 3-pyrrolidinol |
| US5472958A (en) * | 1994-08-29 | 1995-12-05 | Abbott Laboratories | 2-((nitro)phenoxymethyl) heterocyclic compounds that enhance cognitive function |
| DE10135043A1 (de) * | 2001-07-11 | 2003-01-30 | Bayer Cropscience Gmbh | Substituierte 3-Heteroaryl(amino- oder oxy)-pyrrolidin-2-one, Verfahren zu deren Herstellung und Verwendung als Herbizide oder als Pflanzenwachstumsregulatoren |
| JP2010527915A (ja) * | 2007-04-26 | 2010-08-19 | アバロン ファーマシューティカルズ，インコーポレイテッド | 多重環化合物及びその用途 |
-
1968
- 1968-12-23 US US786395A patent/US3577415A/en not_active Expired - Lifetime
-
1969
- 1969-12-16 BR BR215184/69A patent/BR6915184D0/pt unknown
- 1969-12-19 GB GB61970/69A patent/GB1280020A/en not_active Expired
- 1969-12-19 CH CH1895669A patent/CH556335A/xx not_active IP Right Cessation
- 1969-12-22 FR FR696944425A patent/FR2026923B1/fr not_active Expired
- 1969-12-23 DE DE19691964510 patent/DE1964510A1/de active Pending
- 1969-12-23 CA CA070774A patent/CA931572A/en not_active Expired
Cited By (15)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE2757766A1 (de) * | 1976-12-28 | 1978-06-29 | Robins Co Inc A H | 1-substituierte-3-aminoaethoxypyrrolidine, ihre herstellung und verwendung als blutdrucksenkendes mittel |
| EP0107930B1 (en) * | 1982-09-30 | 1990-11-28 | A.H. ROBINS COMPANY, INCORPORATED (a Delaware corporation) | Fused aromatic oxazepinones and sulphur analogues thereof and their preparation and use in counteracting histamine |
| EP0147909A1 (en) * | 1983-12-05 | 1985-07-10 | A.H. Robins Company, Incorporated | Aryloxy-N-(aminoalkyl)-1-pyrrolidine and piperidine carboxamides and carbothioamides having antiarrhythmic activity |
| AU572747B2 (en) * | 1983-12-05 | 1988-05-12 | A.H. Robins Company, Incorporated | Aryloxy-n-(aminoalkyl)-1-pyrrolide and piperidine carboxamides and carbothiomides having antiarrythmic activity |
| US5274097A (en) * | 1988-04-19 | 1993-12-28 | Bayer Aktiengesellschaft | 1,3-disubstituted pyrrolidines |
| US5037841A (en) * | 1988-04-19 | 1991-08-06 | Bayer Aktiengesellschaft | 1,3-disubstituted pyrrolidines |
| EP0338331A1 (de) * | 1988-04-19 | 1989-10-25 | Bayer Ag | 1,3-Disubstituierte Pyrrolidine |
| WO2010059393A1 (en) * | 2008-10-30 | 2010-05-27 | Janssen Pharmaceutica Nv | Serotonin receptor modulators |
| US8575364B2 (en) | 2008-10-30 | 2013-11-05 | Janssen Pharmaceutica Nv | Modulators of serotonin receptor |
| US8642583B2 (en) | 2008-10-30 | 2014-02-04 | Janssen Pharmaceutica Nv | Serotonin receptor modulators |
| US8957059B2 (en) | 2008-10-30 | 2015-02-17 | Janssen Pharmaceutica Nv | Modulators of serotonin receptors |
| US9981909B2 (en) | 2008-10-30 | 2018-05-29 | Janssen Pharmaceutica Nv | Serotonin receptor modulators |
| AU2010335277B2 (en) * | 2009-12-22 | 2016-07-07 | F. Hoffmann-La Roche Ag | Substituted benzamide derivatives |
| US10508107B2 (en) | 2016-03-17 | 2019-12-17 | Hoffmann-La Roche Inc. | Morpholine derivative |
| US11312711B2 (en) | 2016-03-17 | 2022-04-26 | Hoffmann-La Roche Inc. | Morpholine derivative |
Also Published As
| Publication number | Publication date |
|---|---|
| FR2026923B1 (enExample) | 1973-06-08 |
| FR2026923A1 (enExample) | 1970-09-25 |
| US3577415A (en) | 1971-05-04 |
| CA931572A (en) | 1973-08-07 |
| CH556335A (de) | 1974-11-29 |
| BR6915184D0 (pt) | 1973-01-04 |
| GB1280020A (en) | 1972-07-05 |
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