JPH0460988B2 - - Google Patents
Info
- Publication number
- JPH0460988B2 JPH0460988B2 JP10405882A JP10405882A JPH0460988B2 JP H0460988 B2 JPH0460988 B2 JP H0460988B2 JP 10405882 A JP10405882 A JP 10405882A JP 10405882 A JP10405882 A JP 10405882A JP H0460988 B2 JPH0460988 B2 JP H0460988B2
- Authority
- JP
- Japan
- Prior art keywords
- group
- parts
- lower alkyl
- formula
- aminocarbonyl
- 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.)
- Expired
Links
- 150000001875 compounds Chemical class 0.000 claims description 98
- 125000000217 alkyl group Chemical group 0.000 claims description 61
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 54
- 238000000034 method Methods 0.000 claims description 48
- -1 cyano, amino Chemical group 0.000 claims description 39
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 38
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 34
- 239000001257 hydrogen Substances 0.000 claims description 34
- 229910052739 hydrogen Inorganic materials 0.000 claims description 34
- 238000006243 chemical reaction Methods 0.000 claims description 32
- GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 claims description 30
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 28
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 26
- 239000002253 acid Substances 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 23
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 18
- 125000005843 halogen group Chemical group 0.000 claims description 18
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 18
- 125000003118 aryl group Chemical group 0.000 claims description 16
- 150000001412 amines Chemical class 0.000 claims description 15
- 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 13
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 12
- 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 claims description 10
- VNRJGEMERJZKLQ-UHFFFAOYSA-N 2-piperazin-1-ylacetamide Chemical compound NC(=O)CN1CCNCC1 VNRJGEMERJZKLQ-UHFFFAOYSA-N 0.000 claims description 9
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 125000005129 aryl carbonyl group Chemical group 0.000 claims description 9
- 239000003153 chemical reaction reagent Substances 0.000 claims description 9
- 208000028867 ischemia Diseases 0.000 claims description 9
- 239000002904 solvent Substances 0.000 claims description 9
- 229910021529 ammonia Inorganic materials 0.000 claims description 8
- 239000002585 base Substances 0.000 claims description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 7
- 239000012442 inert solvent Substances 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 239000008194 pharmaceutical composition Substances 0.000 claims description 7
- 206010021143 Hypoxia Diseases 0.000 claims description 6
- 150000001350 alkyl halides Chemical class 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 125000000524 functional group Chemical group 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000001424 substituent group Chemical group 0.000 claims description 6
- 230000002378 acidificating effect Effects 0.000 claims description 5
- 125000004104 aryloxy group Chemical group 0.000 claims description 5
- 150000002431 hydrogen Chemical class 0.000 claims description 5
- 239000002609 medium Substances 0.000 claims description 5
- BSJWIZFCTFMJGT-UHFFFAOYSA-N 1-[4,4-bis(4-fluorophenyl)butyl]piperazine-2-carboxamide Chemical compound NC(=O)C1CNCCN1CCCC(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 BSJWIZFCTFMJGT-UHFFFAOYSA-N 0.000 claims description 4
- 125000001769 aryl amino group Chemical group 0.000 claims description 4
- 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 4
- 230000000747 cardiac effect Effects 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000001624 naphthyl group Chemical group 0.000 claims description 4
- 125000004076 pyridyl group Chemical group 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 4
- 206010002660 Anoxia Diseases 0.000 claims description 3
- 241000976983 Anoxia Species 0.000 claims description 3
- 239000003513 alkali Substances 0.000 claims description 3
- 230000007953 anoxia Effects 0.000 claims description 3
- 239000012736 aqueous medium Substances 0.000 claims description 3
- 230000008081 blood perfusion Effects 0.000 claims description 3
- 230000007954 hypoxia Effects 0.000 claims description 3
- 239000002841 Lewis acid Substances 0.000 claims description 2
- 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 2
- 239000012458 free base Substances 0.000 claims description 2
- 150000007517 lewis acids Chemical class 0.000 claims description 2
- 238000004519 manufacturing process Methods 0.000 claims description 2
- 229910052987 metal hydride Inorganic materials 0.000 claims description 2
- 150000004681 metal hydrides Chemical class 0.000 claims description 2
- 210000004165 myocardium Anatomy 0.000 claims description 2
- 231100000252 nontoxic Toxicity 0.000 claims description 2
- 230000003000 nontoxic effect Effects 0.000 claims description 2
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 13
- CUJPFPXNDSIBPG-UHFFFAOYSA-N 1,3-propanediyl Chemical group [CH2]C[CH2] CUJPFPXNDSIBPG-UHFFFAOYSA-N 0.000 claims 2
- 201000010099 disease Diseases 0.000 claims 1
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims 1
- 239000000543 intermediate Substances 0.000 description 125
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 123
- 239000000203 mixture Substances 0.000 description 97
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 83
- 239000000047 product Substances 0.000 description 69
- 239000000243 solution Substances 0.000 description 64
- 238000002844 melting Methods 0.000 description 63
- 230000008018 melting Effects 0.000 description 63
- 239000003480 eluent Substances 0.000 description 54
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 48
- 239000011541 reaction mixture Substances 0.000 description 45
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 41
- 238000003756 stirring Methods 0.000 description 40
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 38
- 229960001701 chloroform Drugs 0.000 description 38
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 30
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 29
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 28
- 238000004440 column chromatography Methods 0.000 description 28
- 239000000741 silica gel Substances 0.000 description 28
- 229910002027 silica gel Inorganic materials 0.000 description 28
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 27
- 239000003054 catalyst Substances 0.000 description 27
- 239000007788 liquid Substances 0.000 description 26
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 24
- 238000001816 cooling Methods 0.000 description 22
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 21
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 21
- 239000000284 extract Substances 0.000 description 19
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 17
- 239000004480 active ingredient Substances 0.000 description 17
- 238000007126 N-alkylation reaction Methods 0.000 description 16
- NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 15
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 14
- 229910000029 sodium carbonate Inorganic materials 0.000 description 14
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
- YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 12
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 12
- 239000012074 organic phase Substances 0.000 description 12
- 239000007858 starting material Substances 0.000 description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 11
- 238000010992 reflux Methods 0.000 description 11
- 238000010438 heat treatment Methods 0.000 description 10
- 239000007787 solid Substances 0.000 description 10
- 150000001732 carboxylic acid derivatives Chemical class 0.000 description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 9
- 238000002360 preparation method Methods 0.000 description 9
- 241000282472 Canis lupus familiaris Species 0.000 description 8
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 8
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 8
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 8
- 239000008346 aqueous phase Substances 0.000 description 8
- 238000005984 hydrogenation reaction Methods 0.000 description 8
- 150000004885 piperazines Chemical class 0.000 description 8
- 239000008280 blood Substances 0.000 description 7
- 210000004369 blood Anatomy 0.000 description 7
- 238000010586 diagram Methods 0.000 description 7
- 150000002148 esters Chemical class 0.000 description 7
- 125000006239 protecting group Chemical group 0.000 description 7
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 6
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- DNIAPMSPPWPWGF-UHFFFAOYSA-N Propylene glycol Chemical compound CC(O)CO DNIAPMSPPWPWGF-UHFFFAOYSA-N 0.000 description 6
- 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 6
- 230000029936 alkylation Effects 0.000 description 6
- 238000005804 alkylation reaction Methods 0.000 description 6
- 150000001408 amides Chemical class 0.000 description 6
- 238000009835 boiling Methods 0.000 description 6
- 210000003748 coronary sinus Anatomy 0.000 description 6
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 6
- LXCFILQKKLGQFO-UHFFFAOYSA-N methylparaben Chemical compound COC(=O)C1=CC=C(O)C=C1 LXCFILQKKLGQFO-UHFFFAOYSA-N 0.000 description 6
- 239000012258 stirred mixture Substances 0.000 description 6
- 239000003826 tablet Substances 0.000 description 6
- 229930192474 thiophene Natural products 0.000 description 6
- XNWFRZJHXBZDAG-UHFFFAOYSA-N 2-METHOXYETHANOL Chemical compound COCCO XNWFRZJHXBZDAG-UHFFFAOYSA-N 0.000 description 5
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 5
- 229960000583 acetic acid Drugs 0.000 description 5
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 5
- 125000004432 carbon atom Chemical group C* 0.000 description 5
- 238000002425 crystallisation Methods 0.000 description 5
- 230000008025 crystallization Effects 0.000 description 5
- 239000003937 drug carrier Substances 0.000 description 5
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 5
- 238000002474 experimental method Methods 0.000 description 5
- 125000004356 hydroxy functional group Chemical group O* 0.000 description 5
- 239000005457 ice water Substances 0.000 description 5
- 238000001990 intravenous administration Methods 0.000 description 5
- 239000003208 petroleum Substances 0.000 description 5
- 125000004193 piperazinyl group Chemical group 0.000 description 5
- FVAUCKIRQBBSSJ-UHFFFAOYSA-M sodium iodide Inorganic materials [Na+].[I-] FVAUCKIRQBBSSJ-UHFFFAOYSA-M 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- OZMORHVDUHRQLL-UHFFFAOYSA-N 1-fluoro-4-[1-(4-fluorophenyl)-4-iodobutyl]benzene Chemical compound C1=CC(F)=CC=C1C(CCCI)C1=CC=C(F)C=C1 OZMORHVDUHRQLL-UHFFFAOYSA-N 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- MFESCIUQSIBMSM-UHFFFAOYSA-N I-BCP Chemical compound ClCCCBr MFESCIUQSIBMSM-UHFFFAOYSA-N 0.000 description 4
- KYQCOXFCLRTKLS-UHFFFAOYSA-N Pyrazine Chemical compound C1=CN=CC=N1 KYQCOXFCLRTKLS-UHFFFAOYSA-N 0.000 description 4
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 4
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 4
- 229920002472 Starch Polymers 0.000 description 4
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
- 125000003158 alcohol group Chemical group 0.000 description 4
- HUMNYLRZRPPJDN-UHFFFAOYSA-N benzaldehyde Chemical compound O=CC1=CC=CC=C1 HUMNYLRZRPPJDN-UHFFFAOYSA-N 0.000 description 4
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 4
- 239000002775 capsule Substances 0.000 description 4
- 230000002612 cardiopulmonary effect Effects 0.000 description 4
- 239000003610 charcoal Substances 0.000 description 4
- 238000001035 drying Methods 0.000 description 4
- 238000001704 evaporation Methods 0.000 description 4
- 238000009472 formulation Methods 0.000 description 4
- 125000002346 iodo group Chemical group I* 0.000 description 4
- QELSKZZBTMNZEB-UHFFFAOYSA-N propylparaben Chemical compound CCCOC(=O)C1=CC=C(O)C=C1 QELSKZZBTMNZEB-UHFFFAOYSA-N 0.000 description 4
- 229920006395 saturated elastomer Polymers 0.000 description 4
- 239000012312 sodium hydride Substances 0.000 description 4
- 229910000104 sodium hydride Inorganic materials 0.000 description 4
- 235000019698 starch Nutrition 0.000 description 4
- FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 4
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 3
- 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 3
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 3
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 3
- 239000000440 bentonite Substances 0.000 description 3
- 229910000278 bentonite Inorganic materials 0.000 description 3
- SVPXDRXYRYOSEX-UHFFFAOYSA-N bentoquatam Chemical compound O.O=[Si]=O.O=[Al]O[Al]=O SVPXDRXYRYOSEX-UHFFFAOYSA-N 0.000 description 3
- 230000037396 body weight Effects 0.000 description 3
- 125000001246 bromo group Chemical group Br* 0.000 description 3
- 125000001309 chloro group Chemical group Cl* 0.000 description 3
- 210000001105 femoral artery Anatomy 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 239000004615 ingredient Substances 0.000 description 3
- 235000014655 lactic acid Nutrition 0.000 description 3
- 235000010270 methyl p-hydroxybenzoate Nutrition 0.000 description 3
- PYLWMHQQBFSUBP-UHFFFAOYSA-N monofluorobenzene Chemical compound FC1=CC=CC=C1 PYLWMHQQBFSUBP-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 239000012299 nitrogen atmosphere Substances 0.000 description 3
- 239000002244 precipitate Substances 0.000 description 3
- 235000010232 propyl p-hydroxybenzoate Nutrition 0.000 description 3
- 229960003415 propylparaben Drugs 0.000 description 3
- 238000000746 purification Methods 0.000 description 3
- 230000008707 rearrangement Effects 0.000 description 3
- 238000006268 reductive amination reaction Methods 0.000 description 3
- 239000011780 sodium chloride Substances 0.000 description 3
- 239000008107 starch Substances 0.000 description 3
- 238000001665 trituration Methods 0.000 description 3
- PRPGZLYWOJPAQZ-UHFFFAOYSA-N (4-fluorophenyl)-[2-(hydroxymethyl)phenyl]methanol Chemical compound OCC1=CC=CC=C1C(O)C1=CC=C(F)C=C1 PRPGZLYWOJPAQZ-UHFFFAOYSA-N 0.000 description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
- BVCJSDGVJGPPLY-UHFFFAOYSA-N 1,4-dibenzyl-2-(methoxymethyl)piperazine Chemical compound C1CN(CC=2C=CC=CC=2)C(COC)CN1CC1=CC=CC=C1 BVCJSDGVJGPPLY-UHFFFAOYSA-N 0.000 description 2
- UFBBMJWPPBNTGA-UHFFFAOYSA-N 1-(4-fluorophenyl)-1,3-dihydro-2-benzofuran Chemical compound C1=CC(F)=CC=C1C1C2=CC=CC=C2CO1 UFBBMJWPPBNTGA-UHFFFAOYSA-N 0.000 description 2
- IMEJYFCEYZLALP-UHFFFAOYSA-N 1-[4,4-bis(4-fluorophenyl)butyl]-2-(methoxymethyl)piperazine Chemical compound COCC1CNCCN1CCCC(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 IMEJYFCEYZLALP-UHFFFAOYSA-N 0.000 description 2
- ZVBLTWFIHCNRKJ-UHFFFAOYSA-N 1-[4-benzyl-2-(methoxymethyl)piperazin-1-yl]-2,2,2-trifluoroethanone Chemical compound C1CN(C(=O)C(F)(F)F)C(COC)CN1CC1=CC=CC=C1 ZVBLTWFIHCNRKJ-UHFFFAOYSA-N 0.000 description 2
- UXXLTPGCINZEFM-UHFFFAOYSA-N 1-[4-chloro-1-(4-fluorophenyl)butyl]-4-fluorobenzene Chemical compound C1=CC(F)=CC=C1C(CCCCl)C1=CC=C(F)C=C1 UXXLTPGCINZEFM-UHFFFAOYSA-N 0.000 description 2
- KEKZCXPIPPSFDE-UHFFFAOYSA-N 1-benzyl-3-(methoxymethyl)piperazine Chemical compound C1CNC(COC)CN1CC1=CC=CC=C1 KEKZCXPIPPSFDE-UHFFFAOYSA-N 0.000 description 2
- BMDBKYIQYZZARN-UHFFFAOYSA-N 2,2,2-trifluoro-1-[2-(methoxymethyl)piperazin-1-yl]ethanone Chemical compound COCC1CNCCN1C(=O)C(F)(F)F BMDBKYIQYZZARN-UHFFFAOYSA-N 0.000 description 2
- JPKIYKWSYBYKIS-UHFFFAOYSA-N 2,2-bis(4-fluorophenyl)acetonitrile Chemical compound C1=CC(F)=CC=C1C(C#N)C1=CC=C(F)C=C1 JPKIYKWSYBYKIS-UHFFFAOYSA-N 0.000 description 2
- JMQGXDAAZNTETE-UHFFFAOYSA-N 2-(3,3-dimethyl-5,6,8,8a-tetrahydro-1h-[1,3]oxazolo[3,4-a]pyrazin-7-yl)-n-(5-fluoro-2-methylphenyl)acetamide Chemical compound CC1=CC=C(F)C=C1NC(=O)CN1CC(COC2(C)C)N2CC1 JMQGXDAAZNTETE-UHFFFAOYSA-N 0.000 description 2
- FJAZVXUPZQSZKI-UHFFFAOYSA-N 2-(4-fluorobenzoyl)benzoic acid Chemical compound OC(=O)C1=CC=CC=C1C(=O)C1=CC=C(F)C=C1 FJAZVXUPZQSZKI-UHFFFAOYSA-N 0.000 description 2
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Landscapes
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Plural Heterocyclic Compounds (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US27662481A | 1981-06-23 | 1981-06-23 | |
| US276624 | 1981-06-23 | ||
| US362814 | 1994-12-22 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| JPS584774A JPS584774A (ja) | 1983-01-11 |
| JPH0460988B2 true JPH0460988B2 (es) | 1992-09-29 |
Family
ID=23057427
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP57104058A Granted JPS584774A (ja) | 1981-06-23 | 1982-06-18 | Ｎ−アリ−ル−ピペラジンアルカンアミド類 |
Country Status (2)
| Country | Link |
|---|---|
| JP (1) | JPS584774A (es) |
| ZA (1) | ZA824428B (es) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CA2657986A1 (en) * | 2000-02-22 | 2001-08-30 | Cv Therapeutics, Inc. | Substituted piperazine compounds |
| DE60329323D1 (de) * | 2003-01-03 | 2009-10-29 | Cv Therapeutics Inc | Substituierte heterozyklische verbindungen |
-
1982
- 1982-06-18 JP JP57104058A patent/JPS584774A/ja active Granted
- 1982-06-22 ZA ZA824428A patent/ZA824428B/xx unknown
Also Published As
| Publication number | Publication date |
|---|---|
| JPS584774A (ja) | 1983-01-11 |
| ZA824428B (en) | 1984-02-29 |
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