DD259189A5

DD259189A5 - Verfahren zur herstellung neuer hydropyridin-derivate

Verfahren zur herstellung neuer hydropyridin-derivate Download PDF

Info

Publication number: DD259189A5
Authority: DD; German Democratic Republic
Prior art keywords: carboxylic acid; salt; hydroxy; ethyl ester; acid ethyl
Prior art date: 1985-08-27

Application number

DD86293839A

Other languages

German (de)

English (en)

Inventor

Georg Von Sprecher

Wolfgang Froestl

Armin Zuest

Original Assignee

Ciba-Geigy Ag,Ch

Priority date

1985-08-27

Filing date

1986-08-25

Publication date

1988-08-17

1986-08-25 Application filed by Ciba-Geigy Ag,Ch filed Critical Ciba-Geigy Ag,Ch

1988-08-17 Publication of DD259189A5 publication Critical patent/DD259189A5/de

Links

238000000034 method Methods 0.000 title claims abstract description 82
238000002360 preparation method Methods 0.000 title claims abstract description 35
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 title claims abstract description 17
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 70
125000004432 carbon atom Chemical group C* 0.000 claims abstract description 39
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 38
125000003545 alkoxy group Chemical group 0.000 claims abstract description 35
125000000217 alkyl group Chemical group 0.000 claims abstract description 28
229910052739 hydrogen Inorganic materials 0.000 claims abstract description 25
239000001257 hydrogen Substances 0.000 claims abstract description 24
229910052736 halogen Inorganic materials 0.000 claims abstract description 22
150000002367 halogens Chemical class 0.000 claims abstract description 22
125000004453 alkoxycarbonyl group Chemical group 0.000 claims abstract description 20
150000002431 hydrogen Chemical class 0.000 claims abstract description 16
125000004423 acyloxy group Chemical group 0.000 claims abstract description 14
125000002947 alkylene group Chemical group 0.000 claims abstract description 13
125000003277 amino group Chemical group 0.000 claims abstract description 11
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 11
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 10
125000001118 alkylidene group Chemical group 0.000 claims abstract description 9
125000005605 benzo group Chemical group 0.000 claims abstract description 9
WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid group Chemical group C(C1=CC=CC=C1)(=O)O WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims abstract description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims abstract description 7
125000005115 alkyl carbamoyl group Chemical group 0.000 claims abstract description 6
229910052799 carbon Inorganic materials 0.000 claims abstract description 4
229920006395 saturated elastomer Polymers 0.000 claims abstract description 4
-1 5-Methoxybenzocyclobuten-1 -yl Chemical group 0.000 claims description 139
150000003839 salts Chemical class 0.000 claims description 134
150000001875 compounds Chemical class 0.000 claims description 112
239000000203 mixture Substances 0.000 claims description 63
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 43
239000002253 acid Substances 0.000 claims description 31
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 19
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 19
125000004429 atom Chemical group 0.000 claims description 14
125000004122 cyclic group Chemical group 0.000 claims description 13
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
125000004093 cyano group Chemical group *C#N 0.000 claims description 6
150000001450 anions Chemical class 0.000 claims description 5
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 claims description 4
125000001841 imino group Chemical group [H]N=* 0.000 claims description 4
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 4
XIWBSOUNZWSFKU-UHFFFAOYSA-N ethyl piperidine-3-carboxylate Chemical compound CCOC(=O)C1CCCNC1 XIWBSOUNZWSFKU-UHFFFAOYSA-N 0.000 claims description 3
125000004129 indan-1-yl group Chemical class [H]C1=C([H])C([H])=C2C(=C1[H])C([H])([H])C([H])([H])C2([H])* 0.000 claims description 3
125000006239 protecting group Chemical group 0.000 claims description 3
VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 2
239000005977 Ethylene Substances 0.000 claims description 2
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 2
LFDJBPPJFWTQOS-UHFFFAOYSA-N ethyl 1-[(5-methoxy-2,3-dihydro-1h-inden-2-yl)methyl]-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)CN1CC1CC2=CC(OC)=CC=C2C1 LFDJBPPJFWTQOS-UHFFFAOYSA-N 0.000 claims description 2
SDYHCWDOLLRGHT-UHFFFAOYSA-N methyl 1-[2-(6-methoxy-2,3-dihydro-1h-inden-1-yl)ethyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OC)=CCCN1CCC1C2=CC(OC)=CC=C2CC1 SDYHCWDOLLRGHT-UHFFFAOYSA-N 0.000 claims description 2
RMZQUHGQYLQKIC-UHFFFAOYSA-N 1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(8),2,4,6-tetraenyl)methyl]piperidine-3-carboxylic acid Chemical compound C12=CC(OC)=CC=C2C=C1CN1CCCC(C(O)=O)C1 RMZQUHGQYLQKIC-UHFFFAOYSA-N 0.000 claims 1
125000003302 alkenyloxy group Chemical group 0.000 claims 1
WUTHWYLJRZFWIT-JCNKGUCWSA-N ethyl (3r,4r)-4-hydroxy-1-[(7-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)methyl]piperidine-3-carboxylate Chemical compound C1C[C@@H](O)[C@H](C(=O)OCC)CN1CC1C2=CC(OC)=CC=C2CCC1 WUTHWYLJRZFWIT-JCNKGUCWSA-N 0.000 claims 1
ZBYKDEIZQLFOCC-UHFFFAOYSA-N ethyl 1-(6-methoxy-2,3-dihydro-1h-inden-1-yl)-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)CN1C1C2=CC(OC)=CC=C2CC1 ZBYKDEIZQLFOCC-UHFFFAOYSA-N 0.000 claims 1
JFBZZYORKLGCOK-UHFFFAOYSA-N ethyl 1-(7-bicyclo[4.2.0]octa-1,3,5,7-tetraenyl)-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)CN1C1=CC2=CC=CC=C12 JFBZZYORKLGCOK-UHFFFAOYSA-N 0.000 claims 1
FXBUXUOZKHERJT-UHFFFAOYSA-N ethyl 1-[(4-chloro-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)methyl]-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)CN1CC1=CC2=CC=C(Cl)C=C12 FXBUXUOZKHERJT-UHFFFAOYSA-N 0.000 claims 1
WLCPBCHFDPDGDI-UHFFFAOYSA-N ethyl 1-[(4-chloro-7-bicyclo[4.2.0]octa-1(8),2,4,6-tetraenyl)methyl]-4-hydroxy-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OCC)=C(O)CCN1CC1=C(C=C(Cl)C=C2)C2=C1 WLCPBCHFDPDGDI-UHFFFAOYSA-N 0.000 claims 1
XEPPCWBHENIJRW-UHFFFAOYSA-N ethyl 1-[(4-methoxy-8-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)methyl]-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)CN1CC1=CC2=CC(OC)=CC=C12 XEPPCWBHENIJRW-UHFFFAOYSA-N 0.000 claims 1
QAOYFXZQEHSYTI-UHFFFAOYSA-N ethyl 1-[(6-methoxy-2,3-dihydro-1h-inden-1-yl)methyl]-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)CN1CC1C2=CC(OC)=CC=C2CC1 QAOYFXZQEHSYTI-UHFFFAOYSA-N 0.000 claims 1
DTECNHFTJJPPCC-UHFFFAOYSA-N ethyl 1-[2-(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4-trienylidene)ethyl]-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)CN1CC=C1C2=CC(OC)=CC=C2C1 DTECNHFTJJPPCC-UHFFFAOYSA-N 0.000 claims 1
HPFSJRSDRANYQS-UHFFFAOYSA-N ethyl 1-[2-(6-methoxy-2,3-dihydro-1h-inden-1-yl)ethyl]-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OCC)CN1CCC1C2=CC(OC)=CC=C2CC1 HPFSJRSDRANYQS-UHFFFAOYSA-N 0.000 claims 1
BTEBPFQFNASPOQ-UHFFFAOYSA-N ethyl 4-iminopiperidine-3-carboxylate Chemical compound CCOC(=O)C1CNCCC1=N BTEBPFQFNASPOQ-UHFFFAOYSA-N 0.000 claims 1
MTUGRKZTMIJTCF-VNCLPFQGSA-N methyl (3r,4r)-4-hydroxy-1-(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)piperidine-3-carboxylate Chemical compound C1C[C@@H](O)[C@H](C(=O)OC)CN1C1CC2=CC(OC)=CC=C2CC1 MTUGRKZTMIJTCF-VNCLPFQGSA-N 0.000 claims 1
GVAVPPMSQKUHIR-UHFFFAOYSA-N methyl 1-(5-methoxy-2,3-dihydro-1h-inden-2-yl)-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OC)=CCCN1C1CC2=CC(OC)=CC=C2C1 GVAVPPMSQKUHIR-UHFFFAOYSA-N 0.000 claims 1
FWXQRMJNMBKTJI-UHFFFAOYSA-N methyl 1-[(5-methoxy-2,3-dihydro-1h-inden-2-yl)methyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OC)=CCCN1CC1CC2=CC(OC)=CC=C2C1 FWXQRMJNMBKTJI-UHFFFAOYSA-N 0.000 claims 1
ZOHQIWWFJAUEMC-UHFFFAOYSA-N methyl 1-[(6-methoxy-2,3-dihydro-1h-inden-1-yl)methyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OC)=CCCN1CC1C2=CC(OC)=CC=C2CC1 ZOHQIWWFJAUEMC-UHFFFAOYSA-N 0.000 claims 1
JTOFVGPEDUADTD-UHFFFAOYSA-N methyl 1-[(6-methoxy-2,3-dihydro-1h-inden-1-yl)methyl]-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OC)CN1CC1C2=CC(OC)=CC=C2CC1 JTOFVGPEDUADTD-UHFFFAOYSA-N 0.000 claims 1
DIAVOXYNTHHDFL-UHFFFAOYSA-N methyl 1-[(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)methyl]-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OC)CN1CC1CC2=CC(OC)=CC=C2CC1 DIAVOXYNTHHDFL-UHFFFAOYSA-N 0.000 claims 1
BFQJBEYGXCVWOG-UHFFFAOYSA-N methyl 1-[2-(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)ethyl]-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OC)CN1CCC1=CC2=CC=C(OC)C=C12 BFQJBEYGXCVWOG-UHFFFAOYSA-N 0.000 claims 1
VVEIESYVPHIUHK-UHFFFAOYSA-N methyl 4-hydroxy-1-[(6-methoxy-2,3-dihydro-1H-inden-1-yl)methyl]-3,6-dihydro-2H-pyridine-5-carboxylate Chemical compound COC(=O)C=1CN(CCC1O)CC1CCC2=CC=C(C=C12)OC VVEIESYVPHIUHK-UHFFFAOYSA-N 0.000 claims 1
JJUATGNHBSSJDC-UHFFFAOYSA-N methyl 4-hydroxy-1-[(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)methyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OC)=C(O)CCN1CC1CC2=CC(OC)=CC=C2CC1 JJUATGNHBSSJDC-UHFFFAOYSA-N 0.000 claims 1
101100490437 Mus musculus Acvrl1 gene Proteins 0.000 abstract 1
150000001721 carbon Chemical group 0.000 abstract 1
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 236
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 190
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 173
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 132
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 117
239000000243 solution Substances 0.000 description 100
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 67
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 66
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 60
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 48
239000007858 starting material Substances 0.000 description 44
239000012074 organic phase Substances 0.000 description 43
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 39
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 39
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 39
239000011541 reaction mixture Substances 0.000 description 39
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 38
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 38
238000003756 stirring Methods 0.000 description 37
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 36
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 35
239000003921 oil Substances 0.000 description 32
235000019198 oils Nutrition 0.000 description 32
229910052938 sodium sulfate Inorganic materials 0.000 description 32
235000011152 sodium sulphate Nutrition 0.000 description 32
XBDQKXXYIPTUBI-UHFFFAOYSA-N Propionic acid Substances CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 29
239000000741 silica gel Substances 0.000 description 28
229910002027 silica gel Inorganic materials 0.000 description 28
238000006243 chemical reaction Methods 0.000 description 27
238000001816 cooling Methods 0.000 description 26
QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 25
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 24
239000002585 base Substances 0.000 description 24
239000002904 solvent Substances 0.000 description 22
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 20
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 20
239000012312 sodium hydride Substances 0.000 description 20
229910000104 sodium hydride Inorganic materials 0.000 description 20
229910052943 magnesium sulfate Inorganic materials 0.000 description 19
235000019341 magnesium sulphate Nutrition 0.000 description 19
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 19
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 18
239000000725 suspension Substances 0.000 description 18
239000004480 active ingredient Substances 0.000 description 17
238000004587 chromatography analysis Methods 0.000 description 17
AFVFQIVMOAPDHO-UHFFFAOYSA-N methanesulfonic acid Substances CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 16
238000011282 treatment Methods 0.000 description 16
239000006185 dispersion Substances 0.000 description 15
125000004494 ethyl ester group Chemical group 0.000 description 15
239000000284 extract Substances 0.000 description 15
238000010992 reflux Methods 0.000 description 15
JIGUQPWFLRLWPJ-UHFFFAOYSA-N Ethyl acrylate Chemical compound CCOC(=O)C=C JIGUQPWFLRLWPJ-UHFFFAOYSA-N 0.000 description 14
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 13
239000002480 mineral oil Substances 0.000 description 13
235000010446 mineral oil Nutrition 0.000 description 13
IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 13
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 12
BAPJBEWLBFYGME-UHFFFAOYSA-N Methyl acrylate Chemical compound COC(=O)C=C BAPJBEWLBFYGME-UHFFFAOYSA-N 0.000 description 12
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
239000012043 crude product Substances 0.000 description 11
239000005457 ice water Substances 0.000 description 11
HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Substances [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 11
230000002378 acidificating effect Effects 0.000 description 10
229910021529 ammonia Inorganic materials 0.000 description 10
QMMFVYPAHWMCMS-UHFFFAOYSA-N Dimethyl sulfide Chemical compound CSC QMMFVYPAHWMCMS-UHFFFAOYSA-N 0.000 description 9
239000012359 Methanesulfonyl chloride Substances 0.000 description 9
229910052783 alkali metal Inorganic materials 0.000 description 9
150000001412 amines Chemical class 0.000 description 9
239000012280 lithium aluminium hydride Substances 0.000 description 9
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 9
239000012279 sodium borohydride Substances 0.000 description 9
229910000033 sodium borohydride Inorganic materials 0.000 description 9
239000003826 tablet Substances 0.000 description 9
239000000454 talc Substances 0.000 description 9
229910052623 talc Inorganic materials 0.000 description 9
235000012222 talc Nutrition 0.000 description 9
XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 8
XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 8
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 8
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 8
PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 8
229920002472 Starch Polymers 0.000 description 8
150000007513 acids Chemical class 0.000 description 8
229910052500 inorganic mineral Inorganic materials 0.000 description 8
239000008101 lactose Substances 0.000 description 8
VNWKTOKETHGBQD-UHFFFAOYSA-N methane Chemical compound C VNWKTOKETHGBQD-UHFFFAOYSA-N 0.000 description 8
OJURWUUOVGOHJZ-UHFFFAOYSA-N methyl 2-[(2-acetyloxyphenyl)methyl-[2-[(2-acetyloxyphenyl)methyl-(2-methoxy-2-oxoethyl)amino]ethyl]amino]acetate Chemical compound C=1C=CC=C(OC(C)=O)C=1CN(CC(=O)OC)CCN(CC(=O)OC)CC1=CC=CC=C1OC(C)=O OJURWUUOVGOHJZ-UHFFFAOYSA-N 0.000 description 8
235000010755 mineral Nutrition 0.000 description 8
239000011707 mineral Substances 0.000 description 8
239000000825 pharmaceutical preparation Substances 0.000 description 8
239000012071 phase Substances 0.000 description 8
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 8
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 8
MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 7
229960000583 acetic acid Drugs 0.000 description 7
239000013543 active substance Substances 0.000 description 7
239000002775 capsule Substances 0.000 description 7
239000003795 chemical substances by application Substances 0.000 description 7
239000000155 melt Substances 0.000 description 7
229940098779 methanesulfonic acid Drugs 0.000 description 7
230000001777 nootropic effect Effects 0.000 description 7
PNJWIWWMYCMZRO-UHFFFAOYSA-N pent‐4‐en‐2‐one Natural products CC(=O)CC=C PNJWIWWMYCMZRO-UHFFFAOYSA-N 0.000 description 7
238000003797 solvolysis reaction Methods 0.000 description 7
235000019698 starch Nutrition 0.000 description 7
CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 description 6
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 6
208000026139 Memory disease Diseases 0.000 description 6
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 6
125000002252 acyl group Chemical group 0.000 description 6
150000003973 alkyl amines Chemical class 0.000 description 6
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FYEJJNCUYDJMNH-GBNZRNLASA-N ethyl (3r,4r)-1-(7-bicyclo[4.2.0]octa-1(8),2,4,6-tetraenylmethyl)-4-methylsulfonyloxypiperidine-3-carboxylate;hydrochloride Chemical compound Cl.C1C[C@@H](OS(C)(=O)=O)[C@H](C(=O)OCC)CN1CC1=CC2=CC=CC=C12 FYEJJNCUYDJMNH-GBNZRNLASA-N 0.000 description 1
KZMAPSUZQICBIM-RTBURBONSA-N ethyl (3r,4r)-4-acetyloxy-1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)methyl]piperidine-3-carboxylate Chemical compound C1C[C@@H](OC(C)=O)[C@H](C(=O)OCC)CN1CC1=CC2=CC=C(OC)C=C12 KZMAPSUZQICBIM-RTBURBONSA-N 0.000 description 1
QCEJPTXCLKCXIW-IAGOWNOFSA-N ethyl (3r,4r)-4-hydroxy-1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)methyl]piperidine-3-carboxylate Chemical compound C1C[C@@H](O)[C@H](C(=O)OCC)CN1CC1=CC2=CC=C(OC)C=C12 QCEJPTXCLKCXIW-IAGOWNOFSA-N 0.000 description 1
JOSAFCVRCXMITE-UHFFFAOYSA-N ethyl 1-(6-methoxy-2,3-dihydro-1H-inden-1-yl)-4-oxopiperidine-3-carboxylate hydrochloride Chemical compound Cl.C1CC(=O)C(C(=O)OCC)CN1C1C2=CC(OC)=CC=C2CC1 JOSAFCVRCXMITE-UHFFFAOYSA-N 0.000 description 1
MNSSVLPBGMNHEX-UHFFFAOYSA-N ethyl 1-(7-bicyclo[4.2.0]octa-1(8),2,4,6-tetraenylmethyl)-4-hydroxy-3,6-dihydro-2H-pyridine-5-carboxylate hydrochloride Chemical compound Cl.C1C(C(=O)OCC)=C(O)CCN1CC1=CC2=CC=CC=C12 MNSSVLPBGMNHEX-UHFFFAOYSA-N 0.000 description 1
SCNWHQUVRCDFNX-UHFFFAOYSA-N ethyl 1-(7-bicyclo[4.2.0]octa-1(8),2,4,6-tetraenylmethyl)-4-hydroxy-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OCC)=C(O)CCN1CC1=C(C=CC=C2)C2=C1 SCNWHQUVRCDFNX-UHFFFAOYSA-N 0.000 description 1
ALWVNDLNOZDPDB-UHFFFAOYSA-N ethyl 1-(7-bicyclo[4.2.0]octa-1,3,5,7-tetraenylmethyl)-4-oxopiperidine-3-carboxylate;hydrochloride Chemical compound Cl.C1CC(=O)C(C(=O)OCC)CN1CC1=CC2=CC=CC=C12 ALWVNDLNOZDPDB-UHFFFAOYSA-N 0.000 description 1
NTVVLLJSRCBEFL-UHFFFAOYSA-N ethyl 1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)methyl]-4-oxopiperidine-3-carboxylate;hydrochloride Chemical compound Cl.C1CC(=O)C(C(=O)OCC)CN1CC1=CC2=CC=C(OC)C=C12 NTVVLLJSRCBEFL-UHFFFAOYSA-N 0.000 description 1
RSHJNFHKDGZJQD-UHFFFAOYSA-N ethyl 1-[(4-methoxy-8-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)methyl]-4-oxopiperidine-3-carboxylate;hydrochloride Chemical compound Cl.C1CC(=O)C(C(=O)OCC)CN1CC1=CC2=CC(OC)=CC=C12 RSHJNFHKDGZJQD-UHFFFAOYSA-N 0.000 description 1
LUMLMMFEYHAGRC-UHFFFAOYSA-N ethyl 1-[2-(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4-trienylidene)ethyl]-4-oxopiperidine-3-carboxylate;hydrochloride Chemical compound Cl.C1CC(=O)C(C(=O)OCC)CN1CC=C1C2=CC(OC)=CC=C2C1 LUMLMMFEYHAGRC-UHFFFAOYSA-N 0.000 description 1
YXXQAWWAJOPZMX-UHFFFAOYSA-M ethyl 4-ethoxy-1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(8),2,4,6-tetraenyl)methyl]pyridin-1-ium-3-carboxylate;4-methylbenzenesulfonate Chemical compound CC1=CC=C(S([O-])(=O)=O)C=C1.C1=C(OCC)C(C(=O)OCC)=C[N+](CC=2C3=CC(OC)=CC=C3C=2)=C1 YXXQAWWAJOPZMX-UHFFFAOYSA-M 0.000 description 1
DJDGDJBYODEQGL-UHFFFAOYSA-N ethyl 4-hydroxy-1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)methyl]piperidine-3-carboxylate;hydrochloride Chemical compound Cl.C1CC(O)C(C(=O)OCC)CN1CC1=CC2=CC=C(OC)C=C12 DJDGDJBYODEQGL-UHFFFAOYSA-N 0.000 description 1
MIRANYBANLDUOZ-UHFFFAOYSA-N ethyl 4-hydroxy-1-[(4-methoxy-7-bicyclo[4.2.0]octa-1(8),2,4,6-tetraenyl)methyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OCC)=C(O)CCN1CC1=C(C=C(OC)C=C2)C2=C1 MIRANYBANLDUOZ-UHFFFAOYSA-N 0.000 description 1
WUTHWYLJRZFWIT-UHFFFAOYSA-N ethyl 4-hydroxy-1-[(7-methoxy-1,2,3,4-tetrahydronaphthalen-1-yl)methyl]piperidine-3-carboxylate Chemical compound C1CC(O)C(C(=O)OCC)CN1CC1C2=CC(OC)=CC=C2CCC1 WUTHWYLJRZFWIT-UHFFFAOYSA-N 0.000 description 1
YLZCHDCWYIEPJG-UHFFFAOYSA-N ethyl 4-hydroxy-1-[2-(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)ethyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OCC)=C(O)CCN1CCC1=CC2=CC=C(OC)C=C12 YLZCHDCWYIEPJG-UHFFFAOYSA-N 0.000 description 1
WJMRXKHVNFRWSK-UHFFFAOYSA-N ethyl 4-hydroxy-1-[2-(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)ethyl]-3,6-dihydro-2h-pyridine-5-carboxylate;hydrochloride Chemical compound Cl.C1C(C(=O)OCC)=C(O)CCN1CCC1=CC2=CC=C(OC)C=C12 WJMRXKHVNFRWSK-UHFFFAOYSA-N 0.000 description 1
URRCBLGXCFTNSR-UHFFFAOYSA-N ethyl 7-methoxy-1,2,3,4-tetrahydronaphthalene-2-carboxylate Chemical compound C1=C(OC)C=C2CC(C(=O)OCC)CCC2=C1 URRCBLGXCFTNSR-UHFFFAOYSA-N 0.000 description 1
RIFGWPKJUGCATF-UHFFFAOYSA-N ethyl chloroformate Chemical compound CCOC(Cl)=O RIFGWPKJUGCATF-UHFFFAOYSA-N 0.000 description 1
LVGKNOAMLMIIKO-QXMHVHEDSA-N ethyl oleate Chemical compound CCCCCCCC\C=C/CCCCCCCC(=O)OCC LVGKNOAMLMIIKO-QXMHVHEDSA-N 0.000 description 1
229940093471 ethyl oleate Drugs 0.000 description 1
YJJCBPAEWVURMJ-UHFFFAOYSA-N ethyl propanoate;hydrochloride Chemical compound Cl.CCOC(=O)CC YJJCBPAEWVURMJ-UHFFFAOYSA-N 0.000 description 1
230000007717 exclusion Effects 0.000 description 1
239000000194 fatty acid Substances 0.000 description 1
229930195729 fatty acid Natural products 0.000 description 1
238000001914 filtration Methods 0.000 description 1
229910052731 fluorine Inorganic materials 0.000 description 1
239000011737 fluorine Substances 0.000 description 1
239000006260 foam Substances 0.000 description 1
238000001640 fractional crystallisation Methods 0.000 description 1
239000001530 fumaric acid Substances 0.000 description 1
239000007789 gas Substances 0.000 description 1
239000007903 gelatin capsule Substances 0.000 description 1
229960002442 glucosamine Drugs 0.000 description 1
238000005469 granulation Methods 0.000 description 1
230000003179 granulation Effects 0.000 description 1
125000004997 halocarbonyl group Chemical group 0.000 description 1
125000005843 halogen group Chemical group 0.000 description 1
IXCSERBJSXMMFS-UHFFFAOYSA-N hcl hcl Chemical compound Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 1
125000003187 heptyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000001072 heteroaryl group Chemical group 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
150000004677 hydrates Chemical class 0.000 description 1
150000003840 hydrochlorides Chemical class 0.000 description 1
229910000042 hydrogen bromide Inorganic materials 0.000 description 1
XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 description 1
230000003301 hydrolyzing effect Effects 0.000 description 1
229940031704 hydroxypropyl methylcellulose phthalate Drugs 0.000 description 1
229920003132 hydroxypropyl methylcellulose phthalate Polymers 0.000 description 1
238000011065 in-situ storage Methods 0.000 description 1
125000003392 indanyl group Chemical group C1(CCC2=CC=CC=C12)* 0.000 description 1
239000012442 inert solvent Substances 0.000 description 1
238000002347 injection Methods 0.000 description 1
239000007924 injection Substances 0.000 description 1
PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 description 1
238000005342 ion exchange Methods 0.000 description 1
229910052742 iron Inorganic materials 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
238000002955 isolation Methods 0.000 description 1
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
150000004658 ketimines Chemical class 0.000 description 1
125000000468 ketone group Chemical group 0.000 description 1
238000002372 labelling Methods 0.000 description 1
239000004922 lacquer Substances 0.000 description 1
159000000003 magnesium salts Chemical class 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
239000011976 maleic acid Substances 0.000 description 1
239000001630 malic acid Substances 0.000 description 1
235000011090 malic acid Nutrition 0.000 description 1
239000000594 mannitol Substances 0.000 description 1
235000010355 mannitol Nutrition 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
229910052987 metal hydride Inorganic materials 0.000 description 1
238000006263 metalation reaction Methods 0.000 description 1
YWOITFUKFOYODT-UHFFFAOYSA-N methanol;sodium Chemical compound [Na].OC YWOITFUKFOYODT-UHFFFAOYSA-N 0.000 description 1
CKMKXSGATOEJDD-UHFFFAOYSA-N methyl 1-(6-methoxy-2,3-dihydro-1h-inden-1-yl)-4-oxopiperidine-3-carboxylate Chemical compound C1CC(=O)C(C(=O)OC)CN1C1C2=CC(OC)=CC=C2CC1 CKMKXSGATOEJDD-UHFFFAOYSA-N 0.000 description 1
TVKGNNSGFACTSB-UHFFFAOYSA-N methyl 1-(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-4-oxopiperidine-3-carboxylate;hydrochloride Chemical compound Cl.C1CC(=O)C(C(=O)OC)CN1C1CC2=CC(OC)=CC=C2CC1 TVKGNNSGFACTSB-UHFFFAOYSA-N 0.000 description 1
KXGSKLBVPJMYNX-UHFFFAOYSA-N methyl 1-[(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)methyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OC)=CCCN1CC1CC2=CC(OC)=CC=C2CC1 KXGSKLBVPJMYNX-UHFFFAOYSA-N 0.000 description 1
MHJJWLQZPPHFRX-UHFFFAOYSA-N methyl 1-[(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)methyl]-4-oxopiperidine-3-carboxylate;hydrochloride Chemical compound Cl.C1CC(=O)C(C(=O)OC)CN1CC1CC2=CC(OC)=CC=C2CC1 MHJJWLQZPPHFRX-UHFFFAOYSA-N 0.000 description 1
DQCMEJMRRQLZEU-UHFFFAOYSA-N methyl 1-[2-(2,3-dihydro-1h-inden-1-yl)ethyl]-3,6-dihydro-2h-pyridine-5-carboxylate Chemical compound C1C(C(=O)OC)=CCCN1CCC1C2=CC=CC=C2CC1 DQCMEJMRRQLZEU-UHFFFAOYSA-N 0.000 description 1
KDDJCILMBYKYBE-UHFFFAOYSA-N methyl 1-[2-(2,3-dihydro-1h-inden-1-yl)ethyl]-3,6-dihydro-2h-pyridine-5-carboxylate;hydrochloride Chemical compound Cl.C1C(C(=O)OC)=CCCN1CCC1C2=CC=CC=C2CC1 KDDJCILMBYKYBE-UHFFFAOYSA-N 0.000 description 1
BKSHUQGSKIAVOY-UHFFFAOYSA-N methyl 1-[2-(4-methoxy-7-bicyclo[4.2.0]octa-1(6),2,4,7-tetraenyl)ethyl]-4-oxopiperidine-3-carboxylate;hydrochloride Chemical compound Cl.C1CC(=O)C(C(=O)OC)CN1CCC1=CC2=CC=C(OC)C=C12 BKSHUQGSKIAVOY-UHFFFAOYSA-N 0.000 description 1
UMDAIZIMODCJRB-UHFFFAOYSA-N methyl 1-[2-(6-methoxy-2,3-dihydro-1h-inden-1-yl)ethyl]-3,6-dihydro-2h-pyridine-5-carboxylate;hydrochloride Chemical compound Cl.C1C(C(=O)OC)=CCCN1CCC1C2=CC(OC)=CC=C2CC1 UMDAIZIMODCJRB-UHFFFAOYSA-N 0.000 description 1
CFRLAXWKACHBTR-UHFFFAOYSA-N methyl 4-hydroxy-1-(7-methoxy-1,2,3,4-tetrahydronaphthalen-2-yl)-3,6-dihydro-2h-pyridine-5-carboxylate;hydrochloride Chemical compound Cl.C1C(C(=O)OC)=C(O)CCN1C1CC2=CC(OC)=CC=C2CC1 CFRLAXWKACHBTR-UHFFFAOYSA-N 0.000 description 1
CJKBZZXRBXKIOK-UHFFFAOYSA-N methyl 5-methoxy-2,3-dihydro-1h-indene-2-carboxylate Chemical compound C1=C(OC)C=C2CC(C(=O)OC)CC2=C1 CJKBZZXRBXKIOK-UHFFFAOYSA-N 0.000 description 1
WRMZEXPQHVTWJA-UHFFFAOYSA-N methyl 5-methoxy-3-oxo-1,2-dihydroindene-2-carboxylate Chemical compound C1=C(OC)C=C2C(=O)C(C(=O)OC)CC2=C1 WRMZEXPQHVTWJA-UHFFFAOYSA-N 0.000 description 1
JXRBXNDFMVNTGU-UHFFFAOYSA-N methyl 6-methoxy-2,3-dihydro-1h-indene-1-carboxylate Chemical compound C1=C(OC)C=C2C(C(=O)OC)CCC2=C1 JXRBXNDFMVNTGU-UHFFFAOYSA-N 0.000 description 1
229920000609 methyl cellulose Polymers 0.000 description 1
XMJHPCRAQCTCFT-UHFFFAOYSA-N methyl chloroformate Chemical compound COC(Cl)=O XMJHPCRAQCTCFT-UHFFFAOYSA-N 0.000 description 1
BQQZKNAQDKIGGZ-UHFFFAOYSA-N methyl piperidine-3-carboxylate;hydrochloride Chemical compound Cl.COC(=O)C1CCCNC1 BQQZKNAQDKIGGZ-UHFFFAOYSA-N 0.000 description 1
239000001923 methylcellulose Substances 0.000 description 1
229960002900 methylcellulose Drugs 0.000 description 1
235000010981 methylcellulose Nutrition 0.000 description 1
244000005700 microbiome Species 0.000 description 1
238000002156 mixing Methods 0.000 description 1
125000002950 monocyclic group Chemical group 0.000 description 1
229910000403 monosodium phosphate Inorganic materials 0.000 description 1
235000019799 monosodium phosphate Nutrition 0.000 description 1
239000012452 mother liquor Substances 0.000 description 1
108700039855 mouse a Proteins 0.000 description 1
ULWOJODHECIZAU-UHFFFAOYSA-N n,n-diethylpropan-2-amine Chemical group CCN(CC)C(C)C ULWOJODHECIZAU-UHFFFAOYSA-N 0.000 description 1
AJUXDFHPVZQOGF-UHFFFAOYSA-N n,n-dimethyl-1-naphthylamine Chemical compound C1=CC=C2C(N(C)C)=CC=CC2=C1 AJUXDFHPVZQOGF-UHFFFAOYSA-N 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
150000002825 nitriles Chemical class 0.000 description 1
QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 description 1
229910000510 noble metal Inorganic materials 0.000 description 1
239000003960 organic solvent Substances 0.000 description 1
239000003791 organic solvent mixture Substances 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
239000012188 paraffin wax Substances 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
230000000737 periodic effect Effects 0.000 description 1
239000003208 petroleum Substances 0.000 description 1
239000000546 pharmaceutical excipient Substances 0.000 description 1
XNGIFLGASWRNHJ-UHFFFAOYSA-L phthalate(2-) Chemical compound [O-]C(=O)C1=CC=CC=C1C([O-])=O XNGIFLGASWRNHJ-UHFFFAOYSA-L 0.000 description 1
239000000049 pigment Substances 0.000 description 1
XIMLAVRHZBUYBE-UHFFFAOYSA-N piperidin-2-one;hydrate;hydrochloride Chemical compound O.Cl.O=C1CCCCN1 XIMLAVRHZBUYBE-UHFFFAOYSA-N 0.000 description 1
239000004014 plasticizer Substances 0.000 description 1
229910052697 platinum Inorganic materials 0.000 description 1
229940093429 polyethylene glycol 6000 Drugs 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
GXBBCEZQOPFZFX-UHFFFAOYSA-N potassium;3-aminopropylazanide Chemical compound [K+].NCCC[NH-] GXBBCEZQOPFZFX-UHFFFAOYSA-N 0.000 description 1
229940116317 potato starch Drugs 0.000 description 1
230000000069 prophylactic effect Effects 0.000 description 1
235000019260 propionic acid Nutrition 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
239000013014 purified material Substances 0.000 description 1
125000001453 quaternary ammonium group Chemical group 0.000 description 1
IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
239000012429 reaction media Substances 0.000 description 1
238000001953 recrystallisation Methods 0.000 description 1
239000011347 resin Substances 0.000 description 1
229920005989 resin Polymers 0.000 description 1
229910052703 rhodium Inorganic materials 0.000 description 1
239000010948 rhodium Substances 0.000 description 1
MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 description 1
235000009566 rice Nutrition 0.000 description 1
229940100486 rice starch Drugs 0.000 description 1
238000007363 ring formation reaction Methods 0.000 description 1
229910052707 ruthenium Inorganic materials 0.000 description 1
238000007127 saponification reaction Methods 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000000926 separation method Methods 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
235000010413 sodium alginate Nutrition 0.000 description 1
239000000661 sodium alginate Substances 0.000 description 1
229940005550 sodium alginate Drugs 0.000 description 1
235000019812 sodium carboxymethyl cellulose Nutrition 0.000 description 1
229920001027 sodium carboxymethylcellulose Polymers 0.000 description 1
BEOOHQFXGBMRKU-UHFFFAOYSA-N sodium cyanoborohydride Chemical compound [Na+].[B-]C#N BEOOHQFXGBMRKU-UHFFFAOYSA-N 0.000 description 1
AJPJDKMHJJGVTQ-UHFFFAOYSA-M sodium dihydrogen phosphate Chemical compound [Na+].OP(O)([O-])=O AJPJDKMHJJGVTQ-UHFFFAOYSA-M 0.000 description 1
QDRKDTQENPPHOJ-UHFFFAOYSA-N sodium ethoxide Chemical compound [Na+].CC[O-] QDRKDTQENPPHOJ-UHFFFAOYSA-N 0.000 description 1
229910001415 sodium ion Inorganic materials 0.000 description 1
239000007901 soft capsule Substances 0.000 description 1
241000894007 species Species 0.000 description 1
KXCAEQNNTZANTK-UHFFFAOYSA-N stannane Chemical class [SnH4] KXCAEQNNTZANTK-UHFFFAOYSA-N 0.000 description 1
125000001424 substituent group Chemical group 0.000 description 1
238000006467 substitution reaction Methods 0.000 description 1
239000005720 sucrose Substances 0.000 description 1
150000008163 sugars Chemical class 0.000 description 1
238000006277 sulfonation reaction Methods 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
FKHIFSZMMVMEQY-UHFFFAOYSA-N talc Chemical compound [Mg+2].[O-][Si]([O-])=O FKHIFSZMMVMEQY-UHFFFAOYSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
YBRBMKDOPFTVDT-UHFFFAOYSA-N tert-butylamine Chemical compound CC(C)(C)N YBRBMKDOPFTVDT-UHFFFAOYSA-N 0.000 description 1
JRMUNVKIHCOMHV-UHFFFAOYSA-M tetrabutylammonium bromide Chemical compound [Br-].CCCC[N+](CCCC)(CCCC)CCCC JRMUNVKIHCOMHV-UHFFFAOYSA-M 0.000 description 1
BRNULMACUQOKMR-UHFFFAOYSA-N thiomorpholine Chemical compound C1CSCCN1 BRNULMACUQOKMR-UHFFFAOYSA-N 0.000 description 1
239000011135 tin Substances 0.000 description 1
229910052718 tin Inorganic materials 0.000 description 1
239000010936 titanium Substances 0.000 description 1
229910052719 titanium Inorganic materials 0.000 description 1
239000004408 titanium dioxide Substances 0.000 description 1
235000010487 tragacanth Nutrition 0.000 description 1
239000000196 tragacanth Substances 0.000 description 1
229940116362 tragacanth Drugs 0.000 description 1
238000005809 transesterification reaction Methods 0.000 description 1
229910052723 transition metal Inorganic materials 0.000 description 1
DBGVGMSCBYYSLD-UHFFFAOYSA-N tributylstannane Chemical compound CCCC[SnH](CCCC)CCCC DBGVGMSCBYYSLD-UHFFFAOYSA-N 0.000 description 1
229940078499 tricalcium phosphate Drugs 0.000 description 1
235000019731 tricalcium phosphate Nutrition 0.000 description 1
229910000391 tricalcium phosphate Inorganic materials 0.000 description 1
125000003866 trichloromethyl group Chemical group ClC(Cl)(Cl)* 0.000 description 1
ILWRPSCZWQJDMK-UHFFFAOYSA-N triethylazanium;chloride Chemical compound Cl.CCN(CC)CC ILWRPSCZWQJDMK-UHFFFAOYSA-N 0.000 description 1
CPRPKIMXLHBUGA-UHFFFAOYSA-N triethyltin Chemical group CC[Sn](CC)CC CPRPKIMXLHBUGA-UHFFFAOYSA-N 0.000 description 1
125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
239000005051 trimethylchlorosilane Substances 0.000 description 1
239000003981 vehicle Substances 0.000 description 1
238000010792 warming Methods 0.000 description 1
238000010626 work up procedure Methods 0.000 description 1
229940102001 zinc bromide Drugs 0.000 description 1