JPS637538B2 - - Google Patents

Info

Publication number: JPS637538B2
Authority: JP; Japan
Prior art keywords: solution; add; hydrochloride; under reduced; reduced pressure
Prior art date: 1973-09-25
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

Application number

JP744484A

Other languages

English (en)

Japanese (ja)

Other versions

JPS59144738A (ja

Inventor

Esu Saari Uorufuretsudo

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Merck and Co Inc

Original Assignee

Merck and Co Inc

Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)

1973-09-25

Filing date

1984-01-20

Publication date

1988-02-17

1984-01-20 Application filed by Merck and Co Inc filed Critical Merck and Co Inc

1984-08-18 Publication of JPS59144738A publication Critical patent/JPS59144738A/ja

1985-04-12 Priority to AU41084/85A priority Critical patent/AU559959B2/en

1988-02-17 Publication of JPS637538B2 publication Critical patent/JPS637538B2/ja

Status Granted legal-status Critical Current

Links

-1 acyclic carboxylic acid Chemical class 0.000 claims description 131
239000002253 acid Substances 0.000 claims description 47
150000001875 compounds Chemical class 0.000 claims description 43
150000003839 salts Chemical class 0.000 claims description 35
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 24
239000001257 hydrogen Substances 0.000 claims description 24
229910052739 hydrogen Inorganic materials 0.000 claims description 24
125000004432 carbon atom Chemical group C* 0.000 claims description 8
125000002252 acyl group Chemical class 0.000 claims description 6
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
125000000217 alkyl group Chemical group 0.000 claims description 4
125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 4
239000004305 biphenyl Substances 0.000 claims description 4
235000010290 biphenyl Nutrition 0.000 claims description 4
125000006267 biphenyl group Chemical group 0.000 claims description 4
ZUOUZKKEUPVFJK-UHFFFAOYSA-N phenylbenzene Natural products C1=CC=CC=C1C1=CC=CC=C1 ZUOUZKKEUPVFJK-UHFFFAOYSA-N 0.000 claims description 4
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 3
150000001734 carboxylic acid salts Chemical group 0.000 claims description 2
230000032050 esterification Effects 0.000 claims description 2
238000005886 esterification reaction Methods 0.000 claims description 2
229910052736 halogen Inorganic materials 0.000 claims description 2
150000002367 halogens Chemical class 0.000 claims description 2
239000000243 solution Substances 0.000 description 240
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 239
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 220
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 158
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 142
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 142
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 112
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 98
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 97
238000004519 manufacturing process Methods 0.000 description 95
229910001868 water Inorganic materials 0.000 description 93
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 87
238000003756 stirring Methods 0.000 description 85
239000000203 mixture Substances 0.000 description 83
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 81
235000019441 ethanol Nutrition 0.000 description 73
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 66
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 63
239000003054 catalyst Substances 0.000 description 56
239000000047 product Substances 0.000 description 56
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 54
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 54
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 53
239000002904 solvent Substances 0.000 description 51
238000001914 filtration Methods 0.000 description 48
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 48
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 47
239000000741 silica gel Substances 0.000 description 46
229910002027 silica gel Inorganic materials 0.000 description 46
239000007787 solid Substances 0.000 description 46
239000012141 concentrate Substances 0.000 description 44
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 43
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 38
239000000284 extract Substances 0.000 description 38
239000007788 liquid Substances 0.000 description 37
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 33
229910000041 hydrogen chloride Inorganic materials 0.000 description 33
239000011541 reaction mixture Substances 0.000 description 33
229910000029 sodium carbonate Inorganic materials 0.000 description 32
238000004809 thin layer chromatography Methods 0.000 description 32
238000004458 analytical method Methods 0.000 description 30
229910052799 carbon Inorganic materials 0.000 description 30
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 29
229960000583 acetic acid Drugs 0.000 description 29
229910052763 palladium Inorganic materials 0.000 description 27
229910052757 nitrogen Inorganic materials 0.000 description 23
239000003921 oil Substances 0.000 description 23
235000019198 oils Nutrition 0.000 description 23
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 21
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 21
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 21
CJCSPKMFHVPWAR-JTQLQIEISA-N alpha-methyl-L-dopa Chemical class OC(=O)[C@](N)(C)CC1=CC=C(O)C(O)=C1 CJCSPKMFHVPWAR-JTQLQIEISA-N 0.000 description 20
238000002844 melting Methods 0.000 description 20
230000008018 melting Effects 0.000 description 20
FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 18
239000002244 precipitate Substances 0.000 description 17
238000010521 absorption reaction Methods 0.000 description 16
238000001035 drying Methods 0.000 description 15
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 14
238000001953 recrystallisation Methods 0.000 description 14
239000011780 sodium chloride Substances 0.000 description 14
239000012453 solvate Substances 0.000 description 14
229960002317 succinimide Drugs 0.000 description 14
DKAGJZJALZXOOV-UHFFFAOYSA-N hydrate;hydrochloride Chemical compound O.Cl DKAGJZJALZXOOV-UHFFFAOYSA-N 0.000 description 13
229910052943 magnesium sulfate Inorganic materials 0.000 description 13
235000019341 magnesium sulphate Nutrition 0.000 description 13
238000000034 method Methods 0.000 description 13
IKHGUXGNUITLKF-UHFFFAOYSA-N Acetaldehyde Chemical compound CC=O IKHGUXGNUITLKF-UHFFFAOYSA-N 0.000 description 12
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
239000002585 base Substances 0.000 description 12
150000002148 esters Chemical class 0.000 description 12
239000007789 gas Substances 0.000 description 12
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 12
239000002002 slurry Substances 0.000 description 11
238000012360 testing method Methods 0.000 description 11
UZFMOKQJFYMBGY-UHFFFAOYSA-N 4-hydroxy-TEMPO Chemical compound CC1(C)CC(O)CC(C)(C)N1[O] UZFMOKQJFYMBGY-UHFFFAOYSA-N 0.000 description 10
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 10
238000000354 decomposition reaction Methods 0.000 description 10
239000004615 ingredient Substances 0.000 description 10
DWKPPFQULDPWHX-VKHMYHEASA-N l-alanyl ester Chemical compound COC(=O)[C@H](C)N DWKPPFQULDPWHX-VKHMYHEASA-N 0.000 description 10
229910021578 Iron(III) chloride Inorganic materials 0.000 description 9
239000012153 distilled water Substances 0.000 description 9
238000001704 evaporation Methods 0.000 description 9
230000008020 evaporation Effects 0.000 description 9
239000005457 ice water Substances 0.000 description 9
RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 description 9
238000001556 precipitation Methods 0.000 description 9
238000010992 reflux Methods 0.000 description 9
239000000126 substance Substances 0.000 description 9
KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical compound O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 description 9
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
239000003610 charcoal Substances 0.000 description 8
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
229920006395 saturated elastomer Polymers 0.000 description 8
239000011734 sodium Substances 0.000 description 8
229910052708 sodium Inorganic materials 0.000 description 8
JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 8
FUOOLUPWFVMBKG-UHFFFAOYSA-N 2-Aminoisobutyric acid Chemical compound CC(C)(N)C(O)=O FUOOLUPWFVMBKG-UHFFFAOYSA-N 0.000 description 7
206010020772 Hypertension Diseases 0.000 description 7
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 7
238000006243 chemical reaction Methods 0.000 description 7
238000004587 chromatography analysis Methods 0.000 description 7
238000010828 elution Methods 0.000 description 7
239000000463 material Substances 0.000 description 7
239000000725 suspension Substances 0.000 description 7
239000000052 vinegar Substances 0.000 description 7
VXJJFIUCQHAHGD-UHFFFAOYSA-N 1-(1-chloroethyl)pyrrolidine-2,5-dione Chemical compound CC(Cl)N1C(=O)CCC1=O VXJJFIUCQHAHGD-UHFFFAOYSA-N 0.000 description 6
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
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 6
241001465754 Metazoa Species 0.000 description 6
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 6
239000012346 acetyl chloride Substances 0.000 description 6
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 6
239000012458 free base 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
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 6
159000000000 sodium salts Chemical class 0.000 description 6
VZCYOOQTPOCHFL-OWOJBTEDSA-N Fumaric acid Chemical compound OC(=O)\C=C\C(O)=O VZCYOOQTPOCHFL-OWOJBTEDSA-N 0.000 description 5
239000005909 Kieselgur Substances 0.000 description 5
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 5
230000000694 effects Effects 0.000 description 5
238000010438 heat treatment Methods 0.000 description 5
XLYOFNOQVPJJNP-ZSJDYOACSA-N heavy water Substances [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 description 5
239000011777 magnesium Substances 0.000 description 5
229910052749 magnesium Inorganic materials 0.000 description 5
230000003287 optical effect Effects 0.000 description 5
235000006408 oxalic acid Nutrition 0.000 description 5
NWUYHJFMYQTDRP-UHFFFAOYSA-N 1,2-bis(ethenyl)benzene;1-ethenyl-2-ethylbenzene;styrene Chemical compound C=CC1=CC=CC=C1.CCC1=CC=CC=C1C=C.C=CC1=CC=CC=C1C=C NWUYHJFMYQTDRP-UHFFFAOYSA-N 0.000 description 4
QFHPUEPQOHXZSF-UHFFFAOYSA-N 2-amino-2-methylpropanoic acid;hydrochloride Chemical compound Cl.CC(C)(N)C(O)=O QFHPUEPQOHXZSF-UHFFFAOYSA-N 0.000 description 4
125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 description 4
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 4
GDFAOVXKHJXLEI-VKHMYHEASA-N N-methyl-L-alanine Chemical compound C[NH2+][C@@H](C)C([O-])=O GDFAOVXKHJXLEI-VKHMYHEASA-N 0.000 description 4
LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 4
230000002378 acidificating effect Effects 0.000 description 4
239000013543 active substance Substances 0.000 description 4
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 4
229910052782 aluminium Inorganic materials 0.000 description 4
230000003276 anti-hypertensive effect Effects 0.000 description 4
239000012223 aqueous fraction Substances 0.000 description 4
239000003729 cation exchange resin Substances 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
238000002425 crystallisation Methods 0.000 description 4
230000008025 crystallization Effects 0.000 description 4
239000003937 drug carrier Substances 0.000 description 4
239000006260 foam Substances 0.000 description 4
238000004108 freeze drying Methods 0.000 description 4
239000007903 gelatin capsule Substances 0.000 description 4
230000014509 gene expression Effects 0.000 description 4
229940091173 hydantoin Drugs 0.000 description 4
238000005984 hydrogenation reaction Methods 0.000 description 4
239000012452 mother liquor Substances 0.000 description 4
229960003966 nicotinamide Drugs 0.000 description 4
239000011570 nicotinamide Substances 0.000 description 4
239000006187 pill Substances 0.000 description 4
239000000843 powder Substances 0.000 description 4
239000000454 talc Substances 0.000 description 4
229910052623 talc Inorganic materials 0.000 description 4
229940095064 tartrate Drugs 0.000 description 4
230000001225 therapeutic effect Effects 0.000 description 4
HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 4
235000021419 vinegar Nutrition 0.000 description 4
238000005406 washing Methods 0.000 description 4
239000011592 zinc chloride Substances 0.000 description 4
235000005074 zinc chloride Nutrition 0.000 description 4
LELWHPFBIHGMGF-UHFFFAOYSA-N 1-(1-chloroethyl)pyrrole-2,5-dione Chemical compound CC(Cl)N1C(=O)C=CC1=O LELWHPFBIHGMGF-UHFFFAOYSA-N 0.000 description 3
ZSLUVFAKFWKJRC-IGMARMGPSA-N 232Th Chemical compound [232Th] ZSLUVFAKFWKJRC-IGMARMGPSA-N 0.000 description 3
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 3
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical class Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 3
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 3
LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 3
229910052776 Thorium Inorganic materials 0.000 description 3
229910021627 Tin(IV) chloride Inorganic materials 0.000 description 3
QNAYBMKLOCPYGJ-UHFFFAOYSA-M alaninate Chemical compound CC(N)C([O-])=O QNAYBMKLOCPYGJ-UHFFFAOYSA-M 0.000 description 3
239000003957 anion exchange resin Substances 0.000 description 3
238000009835 boiling Methods 0.000 description 3
239000001110 calcium chloride Substances 0.000 description 3
229910001628 calcium chloride Inorganic materials 0.000 description 3
239000002775 capsule Substances 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
GGRHYQCXXYLUTL-UHFFFAOYSA-N chloromethyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OCCl GGRHYQCXXYLUTL-UHFFFAOYSA-N 0.000 description 3
238000001816 cooling Methods 0.000 description 3
239000012043 crude product Substances 0.000 description 3
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 3
150000004683 dihydrates Chemical class 0.000 description 3
238000004090 dissolution Methods 0.000 description 3
239000012259 ether extract Substances 0.000 description 3
239000002024 ethyl acetate extract Substances 0.000 description 3
238000000605 extraction Methods 0.000 description 3
239000000706 filtrate Substances 0.000 description 3
239000008101 lactose Substances 0.000 description 3
235000019359 magnesium stearate Nutrition 0.000 description 3
NLKNQRATVPKPDG-UHFFFAOYSA-M potassium iodide Chemical compound [K+].[I-] NLKNQRATVPKPDG-UHFFFAOYSA-M 0.000 description 3
230000001376 precipitating effect Effects 0.000 description 3
230000008569 process Effects 0.000 description 3
239000012047 saturated solution Substances 0.000 description 3
VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 3
NSWICVLRGXOPTD-UHFFFAOYSA-N 3-(chloromethyl)-1-methylimidazolidine-2,4-dione Chemical compound CN1CC(=O)N(CCl)C1=O NSWICVLRGXOPTD-UHFFFAOYSA-N 0.000 description 2
ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 2
UKEXVAGOKJKLLI-RSAXXLAASA-N Cl.OC=1C=C(CC[C@H](N)C(=O)OCCOC2=CC=CC=C2)C=CC1O Chemical compound Cl.OC=1C=C(CC[C@H](N)C(=O)OCCOC2=CC=CC=C2)C=CC1O UKEXVAGOKJKLLI-RSAXXLAASA-N 0.000 description 2
TWRXJAOTZQYOKJ-UHFFFAOYSA-L Magnesium chloride Chemical compound [Mg+2].[Cl-].[Cl-] TWRXJAOTZQYOKJ-UHFFFAOYSA-L 0.000 description 2
125000003047 N-acetyl group Chemical group 0.000 description 2
UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 2
WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
ATUOYWHBWRKTHZ-UHFFFAOYSA-N Propane Chemical compound CCC ATUOYWHBWRKTHZ-UHFFFAOYSA-N 0.000 description 2
WUGQZFFCHPXWKQ-UHFFFAOYSA-N Propanolamine Chemical compound NCCCO WUGQZFFCHPXWKQ-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
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 2
241000384512 Trachichthyidae Species 0.000 description 2
125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
230000009471 action Effects 0.000 description 2
235000001014 amino acid Nutrition 0.000 description 2
150000001413 amino acids Chemical class 0.000 description 2
230000003796 beauty Effects 0.000 description 2
HSDAJNMJOMSNEV-UHFFFAOYSA-N benzyl chloroformate Chemical compound ClC(=O)OCC1=CC=CC=C1 HSDAJNMJOMSNEV-UHFFFAOYSA-N 0.000 description 2
230000037396 body weight Effects 0.000 description 2
BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 2
150000004649 carbonic acid derivatives Chemical class 0.000 description 2
230000008859 change Effects 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
125000001309 chloro group Chemical group Cl* 0.000 description 2
229930002875 chlorophyll Natural products 0.000 description 2
235000019804 chlorophyll Nutrition 0.000 description 2
239000002274 desiccant Substances 0.000 description 2
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 2
OPTDDWCXQQYKGU-UHFFFAOYSA-N diphenyldichloromethane Chemical compound C=1C=CC=CC=1C(Cl)(Cl)C1=CC=CC=C1 OPTDDWCXQQYKGU-UHFFFAOYSA-N 0.000 description 2
229920001971 elastomer Polymers 0.000 description 2
238000009472 formulation Methods 0.000 description 2
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229910000028 potassium bicarbonate Inorganic materials 0.000 description 1
239000011736 potassium bicarbonate Substances 0.000 description 1
239000001103 potassium chloride Substances 0.000 description 1
235000011164 potassium chloride Nutrition 0.000 description 1
TYJJADVDDVDEDZ-UHFFFAOYSA-M potassium hydrogencarbonate Chemical compound [K+].OC([O-])=O TYJJADVDDVDEDZ-UHFFFAOYSA-M 0.000 description 1
239000003755 preservative agent Substances 0.000 description 1
125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
238000012545 processing Methods 0.000 description 1
239000001294 propane Substances 0.000 description 1
230000001698 pyrogenic effect Effects 0.000 description 1
VMXUWOKSQNHOCA-UKTHLTGXSA-N ranitidine Chemical compound [O-][N+](=O)\C=C(/NC)NCCSCC1=CC=C(CN(C)C)O1 VMXUWOKSQNHOCA-UKTHLTGXSA-N 0.000 description 1
239000002994 raw material Substances 0.000 description 1
230000004044 response Effects 0.000 description 1
238000009738 saturating Methods 0.000 description 1
UQDJGEHQDNVPGU-UHFFFAOYSA-N serine phosphoethanolamine Chemical compound [NH3+]CCOP([O-])(=O)OCC([NH3+])C([O-])=O UQDJGEHQDNVPGU-UHFFFAOYSA-N 0.000 description 1
239000008159 sesame oil Substances 0.000 description 1
235000011803 sesame oil Nutrition 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
150000003385 sodium Chemical class 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 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
235000010265 sodium sulphite Nutrition 0.000 description 1
239000008247 solid mixture Substances 0.000 description 1
239000000600 sorbitol Substances 0.000 description 1
235000010356 sorbitol Nutrition 0.000 description 1
239000008107 starch Substances 0.000 description 1
235000019698 starch Nutrition 0.000 description 1
238000010025 steaming Methods 0.000 description 1
239000008117 stearic acid Substances 0.000 description 1
239000012258 stirred mixture Substances 0.000 description 1
JDVPQXZIJDEHAN-UHFFFAOYSA-M succinamate Chemical compound NC(=O)CCC([O-])=O JDVPQXZIJDEHAN-UHFFFAOYSA-M 0.000 description 1
YOEWQQVKRJEPAE-UHFFFAOYSA-L succinylcholine chloride (anhydrous) Chemical compound [Cl-].[Cl-].C[N+](C)(C)CCOC(=O)CCC(=O)OCC[N+](C)(C)C YOEWQQVKRJEPAE-UHFFFAOYSA-L 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
239000000829 suppository Substances 0.000 description 1
239000000375 suspending agent Substances 0.000 description 1
239000003826 tablet Substances 0.000 description 1
235000012222 talc Nutrition 0.000 description 1
238000002560 therapeutic procedure Methods 0.000 description 1
DLFVBJFMPXGRIB-UHFFFAOYSA-N thioacetamide Natural products CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 1
230000001988 toxicity Effects 0.000 description 1
231100000419 toxicity Toxicity 0.000 description 1
KHPCPRHQVVSZAH-UHFFFAOYSA-N trans-cinnamyl beta-D-glucopyranoside Natural products OC1C(O)C(O)C(CO)OC1OCC=CC1=CC=CC=C1 KHPCPRHQVVSZAH-UHFFFAOYSA-N 0.000 description 1
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1

Landscapes

Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Acyclic And Carbocyclic Compounds In Medicinal Compositions (AREA)
Heterocyclic Compounds That Contain Two Or More Ring Oxygen Atoms (AREA)
Pyrrole Compounds (AREA)
Peptides Or Proteins (AREA)

JP744484A 1973-09-25 1984-01-20 アミノ酸エステル Granted JPS59144738A (ja)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
AU41084/85A AU559959B2 (en)	1984-01-20	1985-04-12	Image processing system

Applications Claiming Priority (3)

Application Number	Priority Date	Filing Date
US40060973A	1973-09-25	1973-09-25
US482102		1990-02-20
US400609		1995-03-08

Publications (2)

Publication Number	Publication Date
JPS59144738A JPS59144738A (ja)	1984-08-18
JPS637538B2 true JPS637538B2 (es)	1988-02-17

Family

ID=23584292

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
JP744484A Granted JPS59144738A (ja)	1973-09-25	1984-01-20	アミノ酸エステル
JP744584A Pending JPS59144739A (ja)	1973-09-25	1984-01-20	アミノ酸エステル

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
JP744584A Pending JPS59144739A (ja)	1973-09-25	1984-01-20	アミノ酸エステル

Country Status (3)

Country	Link
JP (2)	JPS59144738A (es)
PL (1)	PL94447B1 (es)
ZA (1)	ZA746038B (es)

1974
- 1974-09-24 PL PL17429674A patent/PL94447B1/pl unknown
- 1974-09-24 ZA ZA00746038A patent/ZA746038B/xx unknown
1984
- 1984-01-20 JP JP744484A patent/JPS59144738A/ja active Granted
- 1984-01-20 JP JP744584A patent/JPS59144739A/ja active Pending

Also Published As

Publication number	Publication date
JPS59144739A (ja)	1984-08-18
ZA746038B (en)	1976-04-28
JPS59144738A (ja)	1984-08-18
PL94447B1 (pl)	1977-08-31

Publication	Publication Date	Title
JP2529172B2 (ja)	1996-08-28	アミノ酸から誘導される新規な光学異性体と、その製造方法と、その医薬への応用
SU818479A3 (ru)	1981-03-30	Способ получени меркаптоацилами-НОКиСлОТ
US3983138A (en)	1976-09-28	Amino acid esters
RU2128160C1 (ru)	1999-03-27	Трометаминная соль (+)-(s)-2-(3-бензоилфенил)пропионовой кислоты, способ ее получения, фармацевтическая композиция
JPH0346463B2 (es)	1991-07-16
FR2513250A1 (fr)	1983-03-25	Nouvelles cyclobutene-3,4-diones substituees
JPH09503214A (ja)	1997-03-31	抗炎症活性及び／又は鎮痛活性を有する硝酸エステル類及びそれらの製造方法
JP2013006839A (ja)	2013-01-10	ペリンドプリル
US4218474A (en)	1980-08-19	Derivatives of L- and DL-4-hydroxyphenylglycine
NZ198826A (en)	1984-07-06	Bicyclic compounds and pharmaceutical compositions
JPH0547538B2 (es)	1993-07-19
FR2473042A1 (fr)	1981-07-10	Nouveaux derives de piperazinone utiles notamment comme intermediaire de synthese des derives de l'enkephaline, et leur preparation
SU1241986A3 (ru)	1986-06-30	Способ получени производных бензамида,их гидрохлоридов или оптических изомеров
US5319096A (en)	1994-06-07	(1H-indol-1-yl)-2-(amino) acetamides and related (1H-indol-1-yl)-(aminoalkyl)amides, pharmaceutical composition and use
US4038411A (en)	1977-07-26	Antihypertensive amino acid esters
JPH0559105B2 (es)	1993-08-30
FR2503709A1 (fr)	1982-10-15	Nouveaux derives piperaziniques contenant un cycle oxirane, leur procede de preparation et leur application en therapeutique
JPH0517439A (ja)	1993-01-26	光学的に活性な二環式イミノ−α−カルボン酸エステルのラセミ体の分割法で得られた化合物
FR2534915A1 (fr)	1984-04-27	Nouveaux derives de 2-(phenoxymethyl)-morpholine, utilisation en therapeutique et procede de preparation
JPS637538B2 (es)	1988-02-17
JPS632545B2 (es)	1988-01-19
US4051169A (en)	1977-09-27	Amino acid esters
RU2004539C1 (ru)	1993-12-15	Полистиролсульфонат 4-[3-[этил[-3-(пропилсульфинил)-пропил) амино)-2-оксипропокси]бензонитрила в виде смеси стереоизомеров или чистого стереоизомера, обладающий антиаритмическим действием
US4143146A (en)	1979-03-06	Esters of α-methyl-3,4-OR-phenylalanines
EP0564499A1 (en)	1993-10-13	Novel amines, process for producing them and medicaments containing said compounds.