DE2553595A1 - Isoindol-derivate - Google Patents
Isoindol-derivateInfo
- Publication number
- DE2553595A1 DE2553595A1 DE19752553595 DE2553595A DE2553595A1 DE 2553595 A1 DE2553595 A1 DE 2553595A1 DE 19752553595 DE19752553595 DE 19752553595 DE 2553595 A DE2553595 A DE 2553595A DE 2553595 A1 DE2553595 A1 DE 2553595A1
- Authority
- DE
- Germany
- Prior art keywords
- chloro
- ethyl
- carboxylic acid
- phenylisoindole
- alkyl
- 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.)
- Withdrawn
Links
- VHMICKWLTGFITH-UHFFFAOYSA-N 2H-isoindole Chemical class C1=CC=CC2=CNC=C21 VHMICKWLTGFITH-UHFFFAOYSA-N 0.000 title 1
- 150000001875 compounds Chemical class 0.000 claims description 135
- 125000000217 alkyl group Chemical group 0.000 claims description 70
- -1 butylmethylamino Chemical group 0.000 claims description 65
- 238000000034 method Methods 0.000 claims description 64
- 239000001257 hydrogen Substances 0.000 claims description 60
- 229910052739 hydrogen Inorganic materials 0.000 claims description 60
- 239000002253 acid Substances 0.000 claims description 54
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 50
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 49
- 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 48
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 47
- 150000002431 hydrogen Chemical class 0.000 claims description 43
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 40
- ZMANZCXQSJIPKH-UHFFFAOYSA-N triethylamine Natural products CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 40
- 229910052757 nitrogen Inorganic materials 0.000 claims description 35
- 230000002829 reductive effect Effects 0.000 claims description 30
- 150000002518 isoindoles Chemical class 0.000 claims description 25
- 238000002360 preparation method Methods 0.000 claims description 25
- 239000007858 starting material Substances 0.000 claims description 25
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 20
- 125000003118 aryl group Chemical group 0.000 claims description 19
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 17
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
- 125000004432 carbon atom Chemical group C* 0.000 claims description 14
- 239000003638 chemical reducing agent Substances 0.000 claims description 14
- 239000000460 chlorine Substances 0.000 claims description 14
- 229910052801 chlorine Inorganic materials 0.000 claims description 14
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 14
- 150000003839 salts Chemical class 0.000 claims description 14
- 239000007787 solid Substances 0.000 claims description 14
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 13
- PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 13
- 229910052731 fluorine Inorganic materials 0.000 claims description 13
- 239000011737 fluorine Substances 0.000 claims description 13
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
- 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 12
- 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 12
- 150000001412 amines Chemical class 0.000 claims description 12
- 150000002148 esters Chemical class 0.000 claims description 12
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 11
- 229910052736 halogen Inorganic materials 0.000 claims description 10
- 150000002367 halogens Chemical class 0.000 claims description 10
- 125000002947 alkylene group Chemical group 0.000 claims description 9
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 8
- 239000001301 oxygen Substances 0.000 claims description 8
- 229910052760 oxygen Inorganic materials 0.000 claims description 8
- 125000006239 protecting group Chemical group 0.000 claims description 8
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 7
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 6
- VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 6
- 239000005977 Ethylene Substances 0.000 claims description 6
- 150000004678 hydrides Chemical class 0.000 claims description 6
- 150000002829 nitrogen Chemical class 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- 125000003545 alkoxy group Chemical group 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims description 5
- 125000003258 trimethylene group Chemical group [H]C([H])([*:2])C([H])([H])C([H])([H])[*:1] 0.000 claims description 5
- 230000001539 anorectic effect Effects 0.000 claims description 4
- 150000004985 diamines Chemical class 0.000 claims description 4
- KJBNKHARGBQFNU-UHFFFAOYSA-N ethyl 5-chloro-2-[3-(n-methylanilino)propyl]-3-phenylisoindole-1-carboxylate Chemical compound C=1C=CC=CC=1C1=C2C=C(Cl)C=CC2=C(C(=O)OCC)N1CCCN(C)C1=CC=CC=C1 KJBNKHARGBQFNU-UHFFFAOYSA-N 0.000 claims description 4
- GGXACZHGRLFVTN-UHFFFAOYSA-N ethyl 2-[3-[bis(2-hydroxyethyl)amino]propyl]-5-chloro-3-phenylisoindole-1-carboxylate Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)OCC)N(CCCN(CCO)CCO)C=1C1=CC=CC=C1 GGXACZHGRLFVTN-UHFFFAOYSA-N 0.000 claims description 3
- LTLBLEMDZRWPIK-UHFFFAOYSA-N ethyl 5-chloro-2-[2-(diethylamino)ethyl]-3-phenylisoindole-1-carboxylate Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)OCC)N(CCN(CC)CC)C=1C1=CC=CC=C1 LTLBLEMDZRWPIK-UHFFFAOYSA-N 0.000 claims description 3
- INIOXOMHSKYVQY-UHFFFAOYSA-N ethyl 5-chloro-3-(4-chlorophenyl)-2-[2-(diethylamino)ethyl]isoindole-1-carboxylate Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)OCC)N(CCN(CC)CC)C=1C1=CC=C(Cl)C=C1 INIOXOMHSKYVQY-UHFFFAOYSA-N 0.000 claims description 3
- 239000007788 liquid Substances 0.000 claims description 3
- 229910052720 vanadium Inorganic materials 0.000 claims description 3
- GXVDGHDPKVFNRI-UHFFFAOYSA-N ethyl 2-[2-(diethylamino)ethyl]-3-phenyl-5-(trifluoromethyl)isoindole-1-carboxylate Chemical compound C=12C=C(C(F)(F)F)C=CC2=C(C(=O)OCC)N(CCN(CC)CC)C=1C1=CC=CC=C1 GXVDGHDPKVFNRI-UHFFFAOYSA-N 0.000 claims description 2
- NFHCBTGZMZZIHK-UHFFFAOYSA-N ethyl 2-[5-[butyl(methyl)amino]-3,3-dimethylpentyl]-5-chloro-3-phenylisoindole-1-carboxylate Chemical compound CCCCN(C)CCC(C)(C)CCN1C(C(=O)OCC)=C2C=CC(Cl)=CC2=C1C1=CC=CC=C1 NFHCBTGZMZZIHK-UHFFFAOYSA-N 0.000 claims description 2
- BVPSSFSWWXSMKD-UHFFFAOYSA-N ethyl 2h-isoindole-1-carboxylate Chemical compound C1=CC=CC2=C(C(=O)OCC)NC=C21 BVPSSFSWWXSMKD-UHFFFAOYSA-N 0.000 claims description 2
- DHQFORWGYNVBFD-UHFFFAOYSA-N ethyl 3-phenyl-2h-isoindole-1-carboxylate Chemical compound C=12C=CC=CC2=C(C(=O)OCC)NC=1C1=CC=CC=C1 DHQFORWGYNVBFD-UHFFFAOYSA-N 0.000 claims description 2
- LMGPLZLYVWQHOL-UHFFFAOYSA-N ethyl 5,7-dichloro-2-[2-(diethylamino)ethyl]-3-phenylisoindole-1-carboxylate Chemical compound C=12C=C(Cl)C=C(Cl)C2=C(C(=O)OCC)N(CCN(CC)CC)C=1C1=CC=CC=C1 LMGPLZLYVWQHOL-UHFFFAOYSA-N 0.000 claims description 2
- LSBGNSAWFVKGFD-UHFFFAOYSA-N ethyl 5-chloro-2-[2-[di(propan-2-yl)amino]ethyl]-3-phenylisoindole-1-carboxylate Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)OCC)N(CCN(C(C)C)C(C)C)C=1C1=CC=CC=C1 LSBGNSAWFVKGFD-UHFFFAOYSA-N 0.000 claims description 2
- GZXRKQGDDHDZPN-UHFFFAOYSA-N ethyl 5-chloro-2-[3-(diethylamino)propyl]-3-phenylisoindole-1-carboxylate Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)OCC)N(CCCN(CC)CC)C=1C1=CC=CC=C1 GZXRKQGDDHDZPN-UHFFFAOYSA-N 0.000 claims description 2
- HJRHORDAXBASDT-UHFFFAOYSA-N ethyl 5-chloro-3-(3,4-dichlorophenyl)-2-[2-(diethylamino)ethyl]isoindole-1-carboxylate Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)OCC)N(CCN(CC)CC)C=1C1=CC=C(Cl)C(Cl)=C1 HJRHORDAXBASDT-UHFFFAOYSA-N 0.000 claims description 2
- FWGRICBTPNQQGE-UHFFFAOYSA-N ethyl 5-chloro-3-phenyl-2-[4-(propan-2-ylamino)pentyl]isoindole-1-carboxylate Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)OCC)N(CCCC(C)NC(C)C)C=1C1=CC=CC=C1 FWGRICBTPNQQGE-UHFFFAOYSA-N 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- GYYLFMRZCRQERN-UHFFFAOYSA-N 5-chloro-2-[2-(diethylamino)ethyl]-n-ethyl-3-phenylisoindole-1-carboxamide Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)NCC)N(CCN(CC)CC)C=1C1=CC=CC=C1 GYYLFMRZCRQERN-UHFFFAOYSA-N 0.000 claims 2
- LDRNLJGRTRWILI-UHFFFAOYSA-N 5-chloro-2-[2-(diethylamino)ethyl]-n-methyl-3-phenylisoindole-1-carboxamide Chemical compound CCN(CC)CCN1C(C(=O)NC)=C2C=CC(Cl)=CC2=C1C1=CC=CC=C1 LDRNLJGRTRWILI-UHFFFAOYSA-N 0.000 claims 2
- CNXICFYQWONCMJ-UHFFFAOYSA-N ethyl 5-chloro-2-[2-(dibutylamino)ethyl]-3-phenylisoindole-1-carboxylate Chemical compound CCCCN(CCCC)CCN1C(C(=O)OCC)=C2C=CC(Cl)=CC2=C1C1=CC=CC=C1 CNXICFYQWONCMJ-UHFFFAOYSA-N 0.000 claims 2
- OPFCHBKDUGIKBK-UHFFFAOYSA-N ethyl 6-chloro-2-[2-(diethylamino)ethyl]-3-phenylisoindole-1-carboxylate Chemical compound C=12C=CC(Cl)=CC2=C(C(=O)OCC)N(CCN(CC)CC)C=1C1=CC=CC=C1 OPFCHBKDUGIKBK-UHFFFAOYSA-N 0.000 claims 2
- CUSVXLOKRWPLLN-UHFFFAOYSA-N propan-2-yl 5-chloro-2-[2-(diethylamino)ethyl]-3-phenylisoindole-1-carboxylate Chemical compound CCN(CC)CCN1C(C(=O)OC(C)C)=C2C=CC(Cl)=CC2=C1C1=CC=CC=C1 CUSVXLOKRWPLLN-UHFFFAOYSA-N 0.000 claims 2
- 125000001424 substituent group Chemical group 0.000 claims 2
- LWJRQLBLYDLYII-UHFFFAOYSA-N 2-methylpropyl 5-chloro-2-[2-(diethylamino)ethyl]-3-phenylisoindole-1-carboxylate Chemical compound CCN(CC)CCN1C(C(=O)OCC(C)C)=C2C=CC(Cl)=CC2=C1C1=CC=CC=C1 LWJRQLBLYDLYII-UHFFFAOYSA-N 0.000 claims 1
- 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 claims 1
- QXAMGWKESXGGNV-UHFFFAOYSA-N 7-(diethylamino)-1-benzopyran-2-one Chemical compound C1=CC(=O)OC2=CC(N(CC)CC)=CC=C21 QXAMGWKESXGGNV-UHFFFAOYSA-N 0.000 claims 1
- 125000003310 benzodiazepinyl group Chemical class N1N=C(C=CC2=C1C=CC=C2)* 0.000 claims 1
- ZJVLPSVFGSNJRW-UHFFFAOYSA-N benzyl 5-chloro-2-[2-(diethylamino)ethyl]-3-phenylisoindole-1-carboxylate Chemical compound C=12C=CC(Cl)=CC2=C(C=2C=CC=CC=2)N(CCN(CC)CC)C=1C(=O)OCC1=CC=CC=C1 ZJVLPSVFGSNJRW-UHFFFAOYSA-N 0.000 claims 1
- 239000000969 carrier Substances 0.000 claims 1
- 125000001309 chloro group Chemical group Cl* 0.000 claims 1
- QPRUWJHECXPAAN-UHFFFAOYSA-N ethyl 2-[3-[bis(2-methoxyethyl)amino]propyl]-5-chloro-3-phenylisoindole-1-carboxylate Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)OCC)N(CCCN(CCOC)CCOC)C=1C1=CC=CC=C1 QPRUWJHECXPAAN-UHFFFAOYSA-N 0.000 claims 1
- UUYRKYSSYOHUOW-UHFFFAOYSA-N ethyl 3-(4-chlorophenyl)-2-[2-(diethylamino)ethyl]isoindole-1-carboxylate Chemical compound C=12C=CC=CC2=C(C(=O)OCC)N(CCN(CC)CC)C=1C1=CC=C(Cl)C=C1 UUYRKYSSYOHUOW-UHFFFAOYSA-N 0.000 claims 1
- BJOREDQILVARTM-UHFFFAOYSA-N ethyl 5-chloro-2-[2-(diethylamino)ethyl]-3-(2-fluorophenyl)isoindole-1-carboxylate Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)OCC)N(CCN(CC)CC)C=1C1=CC=CC=C1F BJOREDQILVARTM-UHFFFAOYSA-N 0.000 claims 1
- CRXURJGMOTVRHA-UHFFFAOYSA-N ethyl 5-chloro-2-[3-(cyclohexylamino)propyl]-3-phenylisoindole-1-carboxylate Chemical compound C=1C=CC=CC=1C1=C2C=C(Cl)C=CC2=C(C(=O)OCC)N1CCCNC1CCCCC1 CRXURJGMOTVRHA-UHFFFAOYSA-N 0.000 claims 1
- 239000004615 ingredient Substances 0.000 claims 1
- 231100000252 nontoxic Toxicity 0.000 claims 1
- 230000003000 nontoxic effect Effects 0.000 claims 1
- 239000000546 pharmaceutical excipient Substances 0.000 claims 1
- 230000001225 therapeutic effect Effects 0.000 claims 1
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 216
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 183
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 115
- 239000000243 solution Substances 0.000 description 98
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 97
- 238000002844 melting Methods 0.000 description 76
- 230000008018 melting Effects 0.000 description 76
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 75
- 229940073584 methylene chloride Drugs 0.000 description 72
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 64
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 48
- 239000000203 mixture Substances 0.000 description 46
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 43
- 229910052938 sodium sulfate Inorganic materials 0.000 description 42
- 235000011152 sodium sulphate Nutrition 0.000 description 42
- 238000006243 chemical reaction Methods 0.000 description 33
- 239000011780 sodium chloride Substances 0.000 description 32
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
- VLKZOEOYAKHREP-UHFFFAOYSA-N hexane Substances CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 30
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 27
- 125000004494 ethyl ester group Chemical group 0.000 description 26
- 239000011541 reaction mixture Substances 0.000 description 26
- 238000001953 recrystallisation Methods 0.000 description 26
- 239000003921 oil Substances 0.000 description 25
- 235000019198 oils Nutrition 0.000 description 25
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 24
- 238000001816 cooling Methods 0.000 description 24
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 20
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 20
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 20
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 19
- 239000005457 ice water Substances 0.000 description 19
- 239000012312 sodium hydride Substances 0.000 description 19
- 229910000104 sodium hydride Inorganic materials 0.000 description 19
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 18
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 18
- 239000012074 organic phase Substances 0.000 description 17
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 16
- 239000000284 extract Substances 0.000 description 16
- 239000003960 organic solvent Substances 0.000 description 16
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 15
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 15
- 239000013078 crystal Substances 0.000 description 15
- 239000000741 silica gel Substances 0.000 description 15
- 229910002027 silica gel Inorganic materials 0.000 description 15
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 14
- 229960000583 acetic acid Drugs 0.000 description 14
- 239000003480 eluent Substances 0.000 description 14
- 239000000047 product Substances 0.000 description 14
- 238000010992 reflux Methods 0.000 description 14
- 238000003756 stirring Methods 0.000 description 14
- GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Chemical compound 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 12
- 239000012362 glacial acetic acid Substances 0.000 description 12
- 239000000725 suspension Substances 0.000 description 12
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 12
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 10
- 229910052783 alkali metal Inorganic materials 0.000 description 10
- 238000002425 crystallisation Methods 0.000 description 10
- 230000008025 crystallization Effects 0.000 description 10
- 239000006185 dispersion Substances 0.000 description 10
- 235000019253 formic acid Nutrition 0.000 description 10
- 239000002480 mineral oil Substances 0.000 description 10
- 235000010446 mineral oil Nutrition 0.000 description 10
- BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- 239000007864 aqueous solution Substances 0.000 description 9
- 229910052786 argon Inorganic materials 0.000 description 9
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 description 9
- 239000010410 layer Substances 0.000 description 9
- 229920006395 saturated elastomer Polymers 0.000 description 9
- 239000002904 solvent Substances 0.000 description 9
- RAGSWDIQBBZLLL-UHFFFAOYSA-N 2-chloroethyl(diethyl)azanium;chloride Chemical compound Cl.CCN(CC)CCCl RAGSWDIQBBZLLL-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 238000001704 evaporation Methods 0.000 description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 description 7
- 229910000029 sodium carbonate Inorganic materials 0.000 description 7
- OIFBSDVPJOWBCH-UHFFFAOYSA-N Diethyl carbonate Chemical compound CCOC(=O)OCC OIFBSDVPJOWBCH-UHFFFAOYSA-N 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 6
- 239000002775 capsule Substances 0.000 description 6
- 239000003795 chemical substances by application Substances 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
- 239000012279 sodium borohydride Substances 0.000 description 6
- 229910000033 sodium borohydride Inorganic materials 0.000 description 6
- BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 6
- 229920002261 Corn starch Polymers 0.000 description 5
- 239000008120 corn starch Substances 0.000 description 5
- JARRFJLRNFBULQ-UHFFFAOYSA-N ethyl 5-chloro-2-[2-(diethylamino)ethyl]-3-phenylisoindole-1-carboxylate;hydrochloride Chemical compound Cl.C=12C=C(Cl)C=CC2=C(C(=O)OCC)N(CCN(CC)CC)C=1C1=CC=CC=C1 JARRFJLRNFBULQ-UHFFFAOYSA-N 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 229910000027 potassium carbonate Inorganic materials 0.000 description 5
- 239000002244 precipitate Substances 0.000 description 5
- 150000003254 radicals Chemical class 0.000 description 5
- 239000012047 saturated solution Substances 0.000 description 5
- QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 5
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- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 1
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- 241001465754 Metazoa Species 0.000 description 1
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- NHNBFGGVMKEFGY-UHFFFAOYSA-N Nitrate Chemical compound [O-][N+]([O-])=O NHNBFGGVMKEFGY-UHFFFAOYSA-N 0.000 description 1
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 description 1
- 241000700159 Rattus Species 0.000 description 1
- 229920002472 Starch Polymers 0.000 description 1
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 150000008065 acid anhydrides Chemical class 0.000 description 1
- 238000005903 acid hydrolysis reaction Methods 0.000 description 1
- 230000001476 alcoholic effect Effects 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 238000005904 alkaline hydrolysis reaction Methods 0.000 description 1
- 125000005907 alkyl ester group Chemical group 0.000 description 1
- 150000001351 alkyl iodides Chemical class 0.000 description 1
- 125000005278 alkyl sulfonyloxy group Chemical group 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 229910021529 ammonia Inorganic materials 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 239000012435 aralkylating agent Substances 0.000 description 1
- 150000004945 aromatic hydrocarbons Chemical class 0.000 description 1
- 125000005279 aryl sulfonyloxy group Chemical group 0.000 description 1
- 235000010323 ascorbic acid Nutrition 0.000 description 1
- 229960005070 ascorbic acid Drugs 0.000 description 1
- 239000011668 ascorbic acid Substances 0.000 description 1
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- 150000001557 benzodiazepines Chemical class 0.000 description 1
- HREXFDIZSAUXBO-UHFFFAOYSA-N benzyl n-(2-bromoethyl)carbamate Chemical compound BrCCNC(=O)OCC1=CC=CC=C1 HREXFDIZSAUXBO-UHFFFAOYSA-N 0.000 description 1
- STLGQBDVSTWGIP-UHFFFAOYSA-N bis(2-methoxyethyl) carbonate Chemical compound COCCOC(=O)OCCOC STLGQBDVSTWGIP-UHFFFAOYSA-N 0.000 description 1
- UXXXZMDJQLPQPH-UHFFFAOYSA-N bis(2-methylpropyl) carbonate Chemical compound CC(C)COC(=O)OCC(C)C UXXXZMDJQLPQPH-UHFFFAOYSA-N 0.000 description 1
- JKJWYKGYGWOAHT-UHFFFAOYSA-N bis(prop-2-enyl) carbonate Chemical compound C=CCOC(=O)OCC=C JKJWYKGYGWOAHT-UHFFFAOYSA-N 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000000872 buffer Substances 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
- 125000001589 carboacyl group Chemical group 0.000 description 1
- 150000001728 carbonyl compounds Chemical class 0.000 description 1
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 1
- 239000012876 carrier material Substances 0.000 description 1
- 238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
- OZECDDHOAMNMQI-UHFFFAOYSA-H cerium(3+);trisulfate Chemical compound [Ce+3].[Ce+3].[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O.[O-]S([O-])(=O)=O OZECDDHOAMNMQI-UHFFFAOYSA-H 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
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- 229960004106 citric acid Drugs 0.000 description 1
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- 238000004140 cleaning Methods 0.000 description 1
- 239000012141 concentrate Substances 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- GCFAUZGWPDYAJN-UHFFFAOYSA-N cyclohexyl 3-phenylprop-2-enoate Chemical compound C=1C=CC=CC=1C=CC(=O)OC1CCCCC1 GCFAUZGWPDYAJN-UHFFFAOYSA-N 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 description 1
- 238000000354 decomposition reaction Methods 0.000 description 1
- 150000008050 dialkyl sulfates Chemical class 0.000 description 1
- PIZLBWGMERQCOC-UHFFFAOYSA-N dibenzyl carbonate Chemical compound C=1C=CC=CC=1COC(=O)OCC1=CC=CC=C1 PIZLBWGMERQCOC-UHFFFAOYSA-N 0.000 description 1
- FYIBPWZEZWVDQB-UHFFFAOYSA-N dicyclohexyl carbonate Chemical compound C1CCCCC1OC(=O)OC1CCCCC1 FYIBPWZEZWVDQB-UHFFFAOYSA-N 0.000 description 1
- ZBCBWPMODOFKDW-UHFFFAOYSA-N diethanolamine Chemical compound OCCNCCO ZBCBWPMODOFKDW-UHFFFAOYSA-N 0.000 description 1
- CCAFPWNGIUBUSD-UHFFFAOYSA-N diethyl sulfoxide Chemical compound CCS(=O)CC CCAFPWNGIUBUSD-UHFFFAOYSA-N 0.000 description 1
- SBZXBUIDTXKZTM-UHFFFAOYSA-N diglyme Chemical compound COCCOCCOC SBZXBUIDTXKZTM-UHFFFAOYSA-N 0.000 description 1
- OKQDSOXFNBWWJL-UHFFFAOYSA-N dihexyl carbonate Chemical compound CCCCCCOC(=O)OCCCCCC OKQDSOXFNBWWJL-UHFFFAOYSA-N 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000003113 dilution method Methods 0.000 description 1
- IEJIGPNLZYLLBP-UHFFFAOYSA-N dimethyl carbonate Chemical compound COC(=O)OC IEJIGPNLZYLLBP-UHFFFAOYSA-N 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- QKIUAMUSENSFQQ-UHFFFAOYSA-N dimethylazanide Chemical compound C[N-]C QKIUAMUSENSFQQ-UHFFFAOYSA-N 0.000 description 1
- 239000002552 dosage form Substances 0.000 description 1
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- 239000000839 emulsion Substances 0.000 description 1
- 239000012259 ether extract Substances 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
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- PGGQCDUTKQCONV-UHFFFAOYSA-N ethyl 2-(2-aminoethyl)-5-chloro-3-phenylisoindole-1-carboxylate Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)OCC)N(CCN)C=1C1=CC=CC=C1 PGGQCDUTKQCONV-UHFFFAOYSA-N 0.000 description 1
- XWPAMFGOWISHSS-UHFFFAOYSA-N ethyl 2-[2-(diethylamino)ethyl]-3-phenyl-5-(trifluoromethyl)isoindole-1-carboxylate;hydrochloride Chemical compound Cl.C=12C=C(C(F)(F)F)C=CC2=C(C(=O)OCC)N(CCN(CC)CC)C=1C1=CC=CC=C1 XWPAMFGOWISHSS-UHFFFAOYSA-N 0.000 description 1
- CPSTZUDOIHUYDZ-UHFFFAOYSA-N ethyl 2-[2-(diethylamino)ethyl]-3-phenylisoindole-1-carboxylate;hydrochloride Chemical compound Cl.C=12C=CC=CC2=C(C(=O)OCC)N(CCN(CC)CC)C=1C1=CC=CC=C1 CPSTZUDOIHUYDZ-UHFFFAOYSA-N 0.000 description 1
- YIVRZUOACQDDIY-UHFFFAOYSA-N ethyl 3-(2-benzoyl-5-chloroanilino)-3-oxo-2-(phenylmethoxycarbonylamino)propanoate Chemical compound C=1C(Cl)=CC=C(C(=O)C=2C=CC=CC=2)C=1NC(=O)C(C(=O)OCC)NC(=O)OCC1=CC=CC=C1 YIVRZUOACQDDIY-UHFFFAOYSA-N 0.000 description 1
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- BNGAOKPBBCKPFJ-UHFFFAOYSA-N ethyl 5-chloro-2-(2-methylsulfonyloxyethyl)-3-phenylisoindole-1-carboxylate Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)OCC)N(CCOS(C)(=O)=O)C=1C1=CC=CC=C1 BNGAOKPBBCKPFJ-UHFFFAOYSA-N 0.000 description 1
- YDSHFBXLZMPFMZ-UHFFFAOYSA-N ethyl 5-chloro-2-(4-oxocyclohexa-1,5-dien-1-yl)-3-phenylisoindole-1-carboxylate Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)OCC)N(C=2C=CC(=O)CC=2)C=1C1=CC=CC=C1 YDSHFBXLZMPFMZ-UHFFFAOYSA-N 0.000 description 1
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- YRKNTPVRCVNFGD-UHFFFAOYSA-N ethyl 5-chloro-3-phenyl-2-[4-(propan-2-ylamino)pentyl]isoindole-1-carboxylate;hydrochloride Chemical compound Cl.C=12C=C(Cl)C=CC2=C(C(=O)OCC)N(CCCC(C)NC(C)C)C=1C1=CC=CC=C1 YRKNTPVRCVNFGD-UHFFFAOYSA-N 0.000 description 1
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- 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
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 1
- 238000007327 hydrogenolysis reaction Methods 0.000 description 1
- UTWGRMYWDUMKNY-UHFFFAOYSA-N indole-1-carboxylic acid Chemical compound C1=CC=C2N(C(=O)O)C=CC2=C1 UTWGRMYWDUMKNY-UHFFFAOYSA-N 0.000 description 1
- 239000011261 inert gas Substances 0.000 description 1
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- INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 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
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- 235000001055 magnesium Nutrition 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
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- 125000005905 mesyloxy group Chemical group 0.000 description 1
- VUQUOGPMUUJORT-UHFFFAOYSA-N methyl 4-methylbenzenesulfonate Chemical compound COS(=O)(=O)C1=CC=C(C)C=C1 VUQUOGPMUUJORT-UHFFFAOYSA-N 0.000 description 1
- YMAYUMRHEXHILQ-UHFFFAOYSA-N methyl 5-chloro-2-[2-(diethylamino)ethyl]-3-phenylisoindole-1-carboxylate;hydrochloride Chemical compound Cl.CCN(CC)CCN1C(C(=O)OC)=C2C=CC(Cl)=CC2=C1C1=CC=CC=C1 YMAYUMRHEXHILQ-UHFFFAOYSA-N 0.000 description 1
- JQINOVWQDJTIFQ-UHFFFAOYSA-N methyl 5-chloro-3-phenyl-2h-isoindole-1-carboxylate Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)OC)NC=1C1=CC=CC=C1 JQINOVWQDJTIFQ-UHFFFAOYSA-N 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
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- XPJFRXRLUAPFNQ-UHFFFAOYSA-N n-benzyl-1-chlorobutan-2-amine Chemical compound CCC(CCl)NCC1=CC=CC=C1 XPJFRXRLUAPFNQ-UHFFFAOYSA-N 0.000 description 1
- WDYFJVKIRVKYID-UHFFFAOYSA-N n-benzyl-5-chloro-3-phenyl-2h-isoindole-1-carboxamide Chemical compound C=12C=C(Cl)C=CC2=C(C(=O)NCC=2C=CC=CC=2)NC=1C1=CC=CC=C1 WDYFJVKIRVKYID-UHFFFAOYSA-N 0.000 description 1
- GWHSVFQLPXJHBX-UHFFFAOYSA-N n-butyl-n-(2-chloroethyl)butan-1-amine Chemical compound CCCCN(CCCl)CCCC GWHSVFQLPXJHBX-UHFFFAOYSA-N 0.000 description 1
- 239000012299 nitrogen atmosphere Substances 0.000 description 1
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 1
- OSDZHDOKXGSWOD-UHFFFAOYSA-N nitroxyl;hydrochloride Chemical compound Cl.O=N OSDZHDOKXGSWOD-UHFFFAOYSA-N 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 230000003204 osmotic effect Effects 0.000 description 1
- 229940116315 oxalic acid Drugs 0.000 description 1
- 235000006408 oxalic acid Nutrition 0.000 description 1
- 230000020477 pH reduction Effects 0.000 description 1
- FJKROLUGYXJWQN-UHFFFAOYSA-N papa-hydroxy-benzoic acid Natural products OC(=O)C1=CC=C(O)C=C1 FJKROLUGYXJWQN-UHFFFAOYSA-N 0.000 description 1
- 238000007911 parenteral administration Methods 0.000 description 1
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
- 235000019271 petrolatum Nutrition 0.000 description 1
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
- UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 description 1
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 description 1
- 125000004193 piperazinyl group Chemical group 0.000 description 1
- 229920001515 polyalkylene glycol Polymers 0.000 description 1
- 239000000843 powder Substances 0.000 description 1
- 239000003755 preservative agent Substances 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 125000006308 propyl amino group Chemical group 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 239000011347 resin Substances 0.000 description 1
- 229920005989 resin Polymers 0.000 description 1
- 229960004889 salicylic acid Drugs 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 0.000 description 1
- JUDUFOKGIZUSFP-UHFFFAOYSA-M silver;4-methylbenzenesulfonate Chemical compound [Ag+].CC1=CC=C(S([O-])(=O)=O)C=C1 JUDUFOKGIZUSFP-UHFFFAOYSA-M 0.000 description 1
- 150000003385 sodium Chemical class 0.000 description 1
- HRZFUMHJMZEROT-UHFFFAOYSA-L sodium disulfite Chemical compound [Na+].[Na+].[O-]S(=O)S([O-])(=O)=O HRZFUMHJMZEROT-UHFFFAOYSA-L 0.000 description 1
- 235000009518 sodium iodide Nutrition 0.000 description 1
- 235000010262 sodium metabisulphite Nutrition 0.000 description 1
- 159000000000 sodium salts Chemical class 0.000 description 1
- 239000003381 stabilizer Substances 0.000 description 1
- 238000010561 standard procedure Methods 0.000 description 1
- 239000008107 starch Substances 0.000 description 1
- 235000019698 starch Nutrition 0.000 description 1
- 230000004936 stimulating effect Effects 0.000 description 1
- 239000000829 suppository Substances 0.000 description 1
- 229960001367 tartaric acid Drugs 0.000 description 1
- 235000002906 tartaric acid Nutrition 0.000 description 1
- 239000011975 tartaric acid Substances 0.000 description 1
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 1
- 125000005424 tosyloxy group Chemical group S(=O)(=O)(C1=CC=C(C)C=C1)O* 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 235000015112 vegetable and seed oil Nutrition 0.000 description 1
- 239000008158 vegetable oil Substances 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
- 238000005303 weighing Methods 0.000 description 1
- 239000000080 wetting agent Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D307/00—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom
- C07D307/77—Heterocyclic compounds containing five-membered rings having one oxygen atom as the only ring hetero atom ortho- or peri-condensed with carbocyclic rings or ring systems
- C07D307/87—Benzo [c] furans; Hydrogenated benzo [c] furans
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Indole Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| CH1579574A CH605749A5 (en) | 1974-11-28 | 1974-11-28 | 2-Aminoalkyl-3-phenyl isoindole derivs |
| CH1234275A CH620431A5 (en) | 1975-09-23 | 1975-09-23 | Process for the preparation of novel isoindole derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| DE2553595A1 true DE2553595A1 (de) | 1976-08-12 |
Family
ID=25710097
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| DE19752553595 Withdrawn DE2553595A1 (de) | 1974-11-28 | 1975-11-28 | Isoindol-derivate |
Country Status (23)
| Country | Link |
|---|---|
| US (1) | US3996374A (en, 2012) |
| JP (1) | JPS51125276A (en, 2012) |
| KR (1) | KR800000530B1 (en, 2012) |
| AR (4) | AR214713A1 (en, 2012) |
| AT (1) | AT352109B (en, 2012) |
| BR (1) | BR7507900A (en, 2012) |
| CA (1) | CA1070698A (en, 2012) |
| DD (1) | DD123459A5 (en, 2012) |
| DE (1) | DE2553595A1 (en, 2012) |
| DK (1) | DK537275A (en, 2012) |
| ES (4) | ES442976A1 (en, 2012) |
| FI (1) | FI753356A7 (en, 2012) |
| FR (1) | FR2292472A1 (en, 2012) |
| GB (3) | GB1526270A (en, 2012) |
| HU (1) | HU173877B (en, 2012) |
| IE (2) | IE42932B1 (en, 2012) |
| IL (1) | IL48441A (en, 2012) |
| LU (1) | LU73870A1 (en, 2012) |
| NL (1) | NL7513935A (en, 2012) |
| NO (1) | NO754001L (en, 2012) |
| NZ (1) | NZ179201A (en, 2012) |
| PH (1) | PH12932A (en, 2012) |
| SE (1) | SE405356B (en, 2012) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997016412A1 (de) * | 1995-10-30 | 1997-05-09 | Basf Aktiengesellschaft | Phenylessigsäurederivate, verfahren und zwischenprodukte zu ihrer herstellung und ihre verwendung zur bekämpfung von schadpilzen und tierischen schädlingen |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4077978A (en) * | 1974-11-28 | 1978-03-07 | Hoffmann-La Roche Inc. | Isoindole derivatives |
| US4122265A (en) * | 1976-05-21 | 1978-10-24 | Hoffmann-La Roche Inc. | Derivatives of 3-phenylisoindole-1-carboxylic acid |
| AT348512B (de) * | 1976-08-02 | 1979-02-26 | Hoffmann La Roche | Verfahren zur herstellung von isoindol- derivaten |
| ES2097583T3 (es) * | 1989-05-17 | 1997-04-01 | Shionogi & Co | Procedimiento de preparacion de derivados de alcoxiiminoacetamida y un intermediario de este procedimiento. |
| US5312988A (en) * | 1993-05-28 | 1994-05-17 | Hoechst Celanese Corporation | Amines derived from THPE |
Family Cites Families (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| NL6612891A (en, 2012) * | 1965-09-15 | 1967-03-16 | ||
| US3466298A (en) * | 1967-03-14 | 1969-09-09 | American Home Prod | Process for the preparation of 2-(2-aminoethyl)isoindolines |
| US3879415A (en) * | 1967-03-30 | 1975-04-22 | Hoffmann La Roche | Novel 2{8 2-(1,3-diazacycloalk-2-enyl){9 benzophenone derivatives and novel 1,3-diazacycloalkenyl {8 2,1-a{9 {0 isoindole derivatives |
-
1975
- 1975-11-07 IL IL48441A patent/IL48441A/xx unknown
- 1975-11-10 NZ NZ179201A patent/NZ179201A/xx unknown
- 1975-11-20 US US05/633,514 patent/US3996374A/en not_active Expired - Lifetime
- 1975-11-25 AR AR261338A patent/AR214713A1/es active
- 1975-11-25 FR FR7535985A patent/FR2292472A1/fr active Granted
- 1975-11-26 DD DD189708A patent/DD123459A5/xx unknown
- 1975-11-26 JP JP50140866A patent/JPS51125276A/ja active Pending
- 1975-11-26 LU LU73870A patent/LU73870A1/xx unknown
- 1975-11-26 ES ES442976A patent/ES442976A1/es not_active Expired
- 1975-11-26 HU HU75HO1854A patent/HU173877B/hu unknown
- 1975-11-26 SE SE7513326A patent/SE405356B/xx unknown
- 1975-11-27 IE IE2583/75A patent/IE42932B1/en unknown
- 1975-11-27 NO NO754001A patent/NO754001L/no unknown
- 1975-11-27 GB GB6708/77A patent/GB1526270A/en not_active Expired
- 1975-11-27 GB GB6707/77A patent/GB1526269A/en not_active Expired
- 1975-11-27 DK DK537275A patent/DK537275A/da not_active Application Discontinuation
- 1975-11-27 BR BR7507900A patent/BR7507900A/pt unknown
- 1975-11-27 GB GB48804/75A patent/GB1526267A/en not_active Expired
- 1975-11-27 KR KR7502590A patent/KR800000530B1/ko not_active Expired
- 1975-11-27 CA CA240,663A patent/CA1070698A/en not_active Expired
- 1975-11-27 IE IE123/79A patent/IE42933B1/en unknown
- 1975-11-27 AT AT903975A patent/AT352109B/de not_active IP Right Cessation
- 1975-11-27 FI FI753356A patent/FI753356A7/fi not_active Application Discontinuation
- 1975-11-28 PH PH17818A patent/PH12932A/en unknown
- 1975-11-28 DE DE19752553595 patent/DE2553595A1/de not_active Withdrawn
- 1975-11-28 NL NL7513935A patent/NL7513935A/xx not_active Application Discontinuation
-
1976
- 1976-07-30 AR AR264149A patent/AR214295A1/es active
- 1976-07-30 AR AR264148A patent/AR219283A1/es active
- 1976-07-30 AR AR264147A patent/AR217808A1/es active
- 1976-09-07 ES ES451295A patent/ES451295A1/es not_active Expired
- 1976-09-07 ES ES451294A patent/ES451294A1/es not_active Expired
- 1976-09-07 ES ES451296A patent/ES451296A1/es not_active Expired
Cited By (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| WO1997016412A1 (de) * | 1995-10-30 | 1997-05-09 | Basf Aktiengesellschaft | Phenylessigsäurederivate, verfahren und zwischenprodukte zu ihrer herstellung und ihre verwendung zur bekämpfung von schadpilzen und tierischen schädlingen |
| US6509379B1 (en) | 1995-10-30 | 2003-01-21 | Basf Aktiengesellschaft | Phenylacetic acid derivatives, process and intermediate products for their preparation, and their use as fungicides and pesticides |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| 8139 | Disposal/non-payment of the annual fee |