CZ284206B6 - Steroidní deriváty a způsob jejich výroby - Google Patents

Info

Publication number

CZ284206B6

CZ284206B6 CZ97900A CZ90097A CZ284206B6 CZ 284206 B6 CZ284206 B6 CZ 284206B6 CZ 97900 A CZ97900 A CZ 97900A CZ 90097 A CZ90097 A CZ 90097A CZ 284206 B6 CZ284206 B6 CZ 284206B6

Authority

CZ

Czechia

Prior art keywords

groups

carbon atoms

amino

group

singlet

Prior art date

1992-04-20

Links

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• 238000004519 manufacturing process Methods 0.000 title claims abstract description 9
• 230000003637 steroidlike Effects 0.000 title abstract 2
• 238000002360 preparation method Methods 0.000 claims abstract description 171
• 238000000034 method Methods 0.000 claims abstract description 111
• 150000003431 steroids Chemical class 0.000 claims abstract description 25
• 239000002253 acid Substances 0.000 claims abstract description 17
• UCDHYFZYUGDETN-UHFFFAOYSA-N cyanophosphonic acid Chemical compound OP(O)(=O)C#N UCDHYFZYUGDETN-UHFFFAOYSA-N 0.000 claims abstract description 8
• -1 halogen atoms amino Chemical group 0.000 claims description 677
• 125000004432 carbon atom Chemical group C* 0.000 claims description 255
• 125000001424 substituent group Chemical group 0.000 claims description 127
• 125000000217 alkyl group Chemical group 0.000 claims description 121
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 117
• 125000003118 aryl group Chemical group 0.000 claims description 89
• 125000003545 alkoxy group Chemical group 0.000 claims description 37
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 33
• 125000000547 substituted alkyl group Chemical group 0.000 claims description 25
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 22
• 125000006615 aromatic heterocyclic group Chemical group 0.000 claims description 22
• 125000005843 halogen group Chemical group 0.000 claims description 22
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 20
• 125000004442 acylamino group Chemical group 0.000 claims description 19
• 125000003282 alkyl amino group Chemical group 0.000 claims description 19
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 17
• 229910052757 nitrogen Inorganic materials 0.000 claims description 16
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 16
• 125000001931 aliphatic group Chemical group 0.000 claims description 14
• 229910052783 alkali metal Inorganic materials 0.000 claims description 13
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 12
• 125000003277 amino group Chemical group 0.000 claims description 11
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 11
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 11
• 125000004429 atom Chemical group 0.000 claims description 10
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 9
• 229910052760 oxygen Inorganic materials 0.000 claims description 9
• 239000001301 oxygen Chemical group 0.000 claims description 9
• 125000005842 heteroatom Chemical group 0.000 claims description 8
• 125000002837 carbocyclic group Chemical group 0.000 claims description 7
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
• QJGQUHMNIGDVPM-UHFFFAOYSA-N nitrogen group Chemical group [N] QJGQUHMNIGDVPM-UHFFFAOYSA-N 0.000 claims description 7
• 125000006413 ring segment Chemical group 0.000 claims description 7
• 125000004986 diarylamino group Chemical group 0.000 claims description 6
• 150000003014 phosphoric acid esters Chemical class 0.000 claims description 6
• 125000006239 protecting group Chemical group 0.000 claims description 6
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 5
• 229910052736 halogen Inorganic materials 0.000 claims description 4
• 150000002367 halogens Chemical class 0.000 claims description 4
• 150000002148 esters Chemical class 0.000 abstract description 23
• 239000000543 intermediate Substances 0.000 abstract description 10
• 210000002307 prostate Anatomy 0.000 abstract description 10
• 206010020880 Hypertrophy Diseases 0.000 abstract description 6
• 238000011282 treatment Methods 0.000 abstract description 6
• 230000000144 pharmacologic effect Effects 0.000 abstract description 5
• 230000001135 feminizing effect Effects 0.000 abstract 1
• 150000001875 compounds Chemical class 0.000 description 324
• 238000006243 chemical reaction Methods 0.000 description 187
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 153
• 238000002329 infrared spectrum Methods 0.000 description 80
• 239000000243 solution Substances 0.000 description 79
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 70
• UYOVRYGHWYJIGX-TXTPUJOMSA-N (8s,9s,10r,13s,14s)-10,13-dimethyl-2,7,8,9,11,12,14,15,16,17-decahydro-1h-cyclopenta[a]phenanthrene-3-carboxylic acid Chemical compound C1C=C2C=C(C(O)=O)CC[C@]2(C)[C@@H]2[C@@H]1[C@@H]1CCC[C@@]1(C)CC2 UYOVRYGHWYJIGX-TXTPUJOMSA-N 0.000 description 69
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 66
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 65
• 239000007858 starting material Substances 0.000 description 62
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical class CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 61
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 61
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 60
• 239000000203 mixture Substances 0.000 description 56
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 55
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 description 54
• 239000011541 reaction mixture Substances 0.000 description 52
• 239000002904 solvent Substances 0.000 description 52
• 235000002639 sodium chloride Nutrition 0.000 description 51
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 49
• 238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 46
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 45
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 40
• 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 description 39
• 230000002829 reductive effect Effects 0.000 description 39
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 38
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 description 37
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 37
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 37
• 125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 description 35
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 34
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 33
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
• 125000000040 m-tolyl group Chemical group [H]C1=C([H])C(*)=C([H])C(=C1[H])C([H])([H])[H] 0.000 description 32
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 31
• 125000004180 3-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(F)=C1[H] 0.000 description 30
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
• JIQNWFBLYKVZFY-UHFFFAOYSA-N methoxycyclohexatriene Chemical compound COC1=C[C]=CC=C1 JIQNWFBLYKVZFY-UHFFFAOYSA-N 0.000 description 30
• 239000002585 base Substances 0.000 description 27
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 26
• 238000001704 evaporation Methods 0.000 description 25
• 230000008020 evaporation Effects 0.000 description 25
• 239000000284 extract Substances 0.000 description 25
• 229920006395 saturated elastomer Polymers 0.000 description 24
• 239000011780 sodium chloride Substances 0.000 description 24
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 22
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 22
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 22
• 150000003839 salts Chemical class 0.000 description 22
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 21
• 125000004179 3-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(Cl)=C1[H] 0.000 description 20
• 238000004587 chromatography analysis Methods 0.000 description 20
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 description 20
• SJPOVWGOESAUHV-YBYOAESISA-N s-pyridin-2-yl (8s,9s,10r,13s,14s,17s)-3-cyano-10,13-dimethyl-2,7,8,9,11,12,14,15,16,17-decahydro-1h-cyclopenta[a]phenanthrene-17-carbothioate Chemical compound O=C([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(CCC(=CC4=CC3)C#N)C)CC[C@@]21C)SC1=CC=CC=N1 SJPOVWGOESAUHV-YBYOAESISA-N 0.000 description 20
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 19
• 238000004821 distillation Methods 0.000 description 19
• 125000003682 3-furyl group Chemical group O1C([H])=C([*])C([H])=C1[H] 0.000 description 18
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 18
• 150000001412 amines Chemical group 0.000 description 18
• 239000012442 inert solvent Substances 0.000 description 18
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 17
• 239000003153 chemical reaction reagent Substances 0.000 description 17
• 229940067157 phenylhydrazine Drugs 0.000 description 17
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 16
• 239000000741 silica gel Substances 0.000 description 16
• 229910002027 silica gel Inorganic materials 0.000 description 16
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 description 15
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 15
• 229910052731 fluorine Inorganic materials 0.000 description 15
• 239000011737 fluorine Substances 0.000 description 15
• 235000011167 hydrochloric acid Nutrition 0.000 description 15
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
• 125000004203 4-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 14
• ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical group NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 14
• 238000004440 column chromatography Methods 0.000 description 14
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 14
• 239000000376 reactant Substances 0.000 description 14
• 150000002170 ethers Chemical class 0.000 description 13
• 239000007788 liquid Substances 0.000 description 13
• 125000004208 3-hydroxyphenyl group Chemical group [H]OC1=C([H])C([H])=C([H])C(*)=C1[H] 0.000 description 12
• 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 12
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 12
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 12
• UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 description 12
• 238000001953 recrystallisation Methods 0.000 description 12
• 125000001544 thienyl group Chemical group 0.000 description 12
• RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 12
• LJGHYPLBDBRCRZ-UHFFFAOYSA-N 3-(3-aminophenyl)sulfonylaniline Chemical compound NC1=CC=CC(S(=O)(=O)C=2C=C(N)C=CC=2)=C1 LJGHYPLBDBRCRZ-UHFFFAOYSA-N 0.000 description 11
• 125000006284 3-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C(F)=C1[H])C([H])([H])* 0.000 description 11
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 11
• 125000004176 4-fluorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1F)C([H])([H])* 0.000 description 11
• 150000008065 acid anhydrides Chemical class 0.000 description 11
• LYCAIKOWRPUZTN-UHFFFAOYSA-N ethylene glycol Natural products OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 11
• 231100000989 no adverse effect Toxicity 0.000 description 11
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 11
• 235000017557 sodium bicarbonate Nutrition 0.000 description 11
• 125000006181 4-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1C([H])([H])[H])C([H])([H])* 0.000 description 10
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 10
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 10
• XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 description 10
• 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 10
• 150000001408 amides Chemical class 0.000 description 10
• 230000015572 biosynthetic process Effects 0.000 description 10
• 150000001732 carboxylic acid derivatives Chemical class 0.000 description 10
• 239000003795 chemical substances by application Substances 0.000 description 10
• 125000000753 cycloalkyl group Chemical group 0.000 description 10
• 125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 10
• 125000002541 furyl group Chemical group 0.000 description 10
• AWZOMWXBNJOSBD-YFWFAHHUSA-N (8s,9s,10r,13s,14s,17s)-3-cyano-10,13-dimethyl-2,7,8,9,11,12,14,15,16,17-decahydro-1h-cyclopenta[a]phenanthrene-17-carboxylic acid Chemical compound C1=C(C#N)CC[C@]2(C)[C@H]3CC[C@](C)([C@H](CC4)C(O)=O)[C@@H]4[C@@H]3CC=C21 AWZOMWXBNJOSBD-YFWFAHHUSA-N 0.000 description 9
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 9
• 125000006497 3-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 description 9
• OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 9
• 125000001309 chloro group Chemical group Cl* 0.000 description 9
• 239000003480 eluent Substances 0.000 description 9
• 150000008282 halocarbons Chemical class 0.000 description 9
• 239000002244 precipitate Substances 0.000 description 9
• 238000003786 synthesis reaction Methods 0.000 description 9
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical group CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 8
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 8
• 150000004945 aromatic hydrocarbons Chemical class 0.000 description 8
• 239000000460 chlorine Substances 0.000 description 8
• 229910052801 chlorine Inorganic materials 0.000 description 8
• 238000006460 hydrolysis reaction Methods 0.000 description 8
• 239000003960 organic solvent Substances 0.000 description 8
• QJPQVXSHYBGQGM-UHFFFAOYSA-N palladium;triphenylphosphane Chemical compound [Pd].C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1.C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 QJPQVXSHYBGQGM-UHFFFAOYSA-N 0.000 description 8
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
• 125000006180 3-methyl benzyl group Chemical group [H]C1=C([H])C(=C([H])C(=C1[H])C([H])([H])[H])C([H])([H])* 0.000 description 7
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 7
• 108010066551 Cholestenone 5 alpha-Reductase Proteins 0.000 description 7
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 7
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 7
• 241000700159 Rattus Species 0.000 description 7
• 229910052799 carbon Inorganic materials 0.000 description 7
• 239000003054 catalyst Substances 0.000 description 7
• 239000013078 crystal Substances 0.000 description 7
• 238000001914 filtration Methods 0.000 description 7
• 229910052739 hydrogen Inorganic materials 0.000 description 7
• 230000007062 hydrolysis Effects 0.000 description 7
• 125000005633 phthalidyl group Chemical group 0.000 description 7
• 238000001179 sorption measurement Methods 0.000 description 7
• 238000012360 testing method Methods 0.000 description 7
• 239000008096 xylene Substances 0.000 description 7
• 125000006283 4-chlorobenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1Cl)C([H])([H])* 0.000 description 6
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical group CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 6
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 6
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical group CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 6
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 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
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 6
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 6
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 description 6
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 6
• 125000002252 acyl group Chemical group 0.000 description 6
• 238000007796 conventional method Methods 0.000 description 6
• 238000001816 cooling Methods 0.000 description 6
• ZWWWLCMDTZFSOO-UHFFFAOYSA-N diethoxyphosphorylformonitrile Chemical compound CCOP(=O)(C#N)OCC ZWWWLCMDTZFSOO-UHFFFAOYSA-N 0.000 description 6
• GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 6
• UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
• 238000003756 stirring Methods 0.000 description 6
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 6
• WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 description 6
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• FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 description 1
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• XAEFZNCEHLXOMS-UHFFFAOYSA-M potassium benzoate Chemical compound [K+].[O-]C(=O)C1=CC=CC=C1 XAEFZNCEHLXOMS-UHFFFAOYSA-M 0.000 description 1
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• NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
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• USHAGKDGDHPEEY-UHFFFAOYSA-L potassium persulfate Chemical compound [K+].[K+].[O-]S(=O)(=O)OOS([O-])(=O)=O USHAGKDGDHPEEY-UHFFFAOYSA-L 0.000 description 1
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• 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
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• 238000011160 research Methods 0.000 description 1
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• 229940075562 sodium phosphate dihydrate Drugs 0.000 description 1
• AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
• 235000019345 sodium thiosulphate Nutrition 0.000 description 1
• 239000007787 solid Substances 0.000 description 1
• 238000001228 spectrum Methods 0.000 description 1
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• 230000000707 stereoselective effect Effects 0.000 description 1
• 239000005720 sucrose Substances 0.000 description 1
• 229940124530 sulfonamide Drugs 0.000 description 1
• 150000003456 sulfonamides Chemical class 0.000 description 1
• AKEJUJNQAAGONA-UHFFFAOYSA-N sulfur trioxide Inorganic materials O=S(=O)=O AKEJUJNQAAGONA-UHFFFAOYSA-N 0.000 description 1
• 239000000829 suppository Substances 0.000 description 1
• 208000024891 symptom Diseases 0.000 description 1
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• 229960003604 testosterone Drugs 0.000 description 1
• NHGXDBSUJJNIRV-UHFFFAOYSA-M tetrabutylammonium chloride Chemical compound [Cl-].CCCC[N+](CCCC)(CCCC)CCCC NHGXDBSUJJNIRV-UHFFFAOYSA-M 0.000 description 1
• 238000002560 therapeutic procedure Methods 0.000 description 1
• 125000000335 thiazolyl group Chemical group 0.000 description 1
• HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
• XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
• 125000003944 tolyl group Chemical group 0.000 description 1
• TUQOTMZNTHZOKS-UHFFFAOYSA-N tributylphosphine Chemical compound CCCCP(CCCC)CCCC TUQOTMZNTHZOKS-UHFFFAOYSA-N 0.000 description 1
• IMNIMPAHZVJRPE-UHFFFAOYSA-N triethylenediamine Chemical compound C1CN2CCN1CC2 IMNIMPAHZVJRPE-UHFFFAOYSA-N 0.000 description 1
• 125000005951 trifluoromethanesulfonyloxy group Chemical group 0.000 description 1
• 125000001889 triflyl group Chemical group FC(F)(F)S(*)(=O)=O 0.000 description 1
• 125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 1
• CRKADHVTAQCXRA-UHFFFAOYSA-K trisodium;phosphate;dihydrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]P([O-])([O-])=O CRKADHVTAQCXRA-UHFFFAOYSA-K 0.000 description 1
• 125000002221 trityl group Chemical group [H]C1=C([H])C([H])=C([H])C([H])=C1C([*])(C1=C(C(=C(C(=C1[H])[H])[H])[H])[H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
• JABYJIQOLGWMQW-UHFFFAOYSA-N undec-4-ene Chemical compound CCCCCCC=CCCC JABYJIQOLGWMQW-UHFFFAOYSA-N 0.000 description 1
• 239000011592 zinc chloride Substances 0.000 description 1
• 235000005074 zinc chloride Nutrition 0.000 description 1