CA2871314A1 - Procede de preparation de steroides 17-substitues - Google Patents

Procede de preparation de steroides 17-substitues Download PDF

Info

Publication number: CA2871314A1
Authority: CA; Canada
Prior art keywords: compound; formula; process according; group; protecting group
Prior art date: 2012-04-23
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.): Abandoned

Application number

CA2871314A

Other languages

English (en)

Inventor

Erwin Schreiner

Craig E. Dixon

Boris Gorin

Qingbo LU

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.)

Alphora Research Inc

Original Assignee

Alphora Research 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.)

2012-04-23

Filing date

2013-04-22

Publication date

2013-10-31

2013-04-22 Application filed by Alphora Research Inc filed Critical Alphora Research Inc

2013-10-31 Publication of CA2871314A1 publication Critical patent/CA2871314A1/fr

Status Abandoned legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 100
230000008569 process Effects 0.000 title claims abstract description 90
238000002360 preparation method Methods 0.000 title claims abstract description 16
150000003431 steroids Chemical class 0.000 title abstract description 6
150000001875 compounds Chemical class 0.000 claims description 159
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical group CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims description 60
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 49
239000002904 solvent Substances 0.000 claims description 39
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 38
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 34
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 33
125000006241 alcohol protecting group Chemical group 0.000 claims description 29
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical class CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 26
125000003118 aryl group Chemical group 0.000 claims description 25
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 24
125000006239 protecting group Chemical group 0.000 claims description 24
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 22
239000002253 acid Substances 0.000 claims description 19
238000004128 high performance liquid chromatography Methods 0.000 claims description 19
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 19
125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 18
-1 3-substituted pyridinyl Chemical group 0.000 claims description 17
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 16
125000001072 heteroaryl group Chemical group 0.000 claims description 16
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 15
229910052760 oxygen Inorganic materials 0.000 claims description 15
239000001301 oxygen Substances 0.000 claims description 15
229960004103 abiraterone acetate Drugs 0.000 claims description 14
UVIQSJCZCSLXRZ-UBUQANBQSA-N abiraterone acetate Chemical compound C([C@@H]1[C@]2(C)CC[C@@H]3[C@@]4(C)CC[C@@H](CC4=CC[C@H]31)OC(=O)C)C=C2C1=CC=CN=C1 UVIQSJCZCSLXRZ-UBUQANBQSA-N 0.000 claims description 14
239000002585 base Substances 0.000 claims description 14
125000002252 acyl group Chemical group 0.000 claims description 12
229910052783 alkali metal Inorganic materials 0.000 claims description 12
150000001340 alkali metals Chemical group 0.000 claims description 12
125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 12
125000004076 pyridyl group Chemical group 0.000 claims description 9
229910052784 alkaline earth metal Inorganic materials 0.000 claims description 8
229910052723 transition metal Inorganic materials 0.000 claims description 8
150000003624 transition metals Chemical class 0.000 claims description 8
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 7
238000000746 purification Methods 0.000 claims description 7
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 claims description 6
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 6
238000007259 addition reaction Methods 0.000 claims description 5
230000000397 acetylating effect Effects 0.000 claims description 3
125000003944 tolyl group Chemical group 0.000 claims description 2
239000000543 intermediate Chemical class 0.000 abstract description 4
206010060862 Prostate cancer Diseases 0.000 abstract description 2
208000000236 Prostatic Neoplasms Diseases 0.000 abstract description 2
239000003098 androgen Substances 0.000 abstract description 2
208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract 2
206010006187 Breast cancer Diseases 0.000 abstract 1
208000026310 Breast neoplasm Diseases 0.000 abstract 1
230000001419 dependent effect Effects 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 35
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 24
238000006243 chemical reaction Methods 0.000 description 22
239000000243 solution Substances 0.000 description 21
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
239000011541 reaction mixture Substances 0.000 description 19
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 18
239000000203 mixture Substances 0.000 description 17
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 15
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 13
SRVFFFJZQVENJC-IHRRRGAJSA-N aloxistatin Chemical compound CCOC(=O)[C@H]1O[C@@H]1C(=O)N[C@@H](CC(C)C)C(=O)NCCC(C)C SRVFFFJZQVENJC-IHRRRGAJSA-N 0.000 description 13
239000007787 solid Substances 0.000 description 11
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 10
230000015572 biosynthetic process Effects 0.000 description 10
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 9
125000000217 alkyl group Chemical group 0.000 description 9
238000006297 dehydration reaction Methods 0.000 description 9
238000001914 filtration Methods 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
LCGLNKUTAGEVQW-UHFFFAOYSA-N Dimethyl ether Chemical compound COC LCGLNKUTAGEVQW-UHFFFAOYSA-N 0.000 description 8
239000012359 Methanesulfonyl chloride Substances 0.000 description 8
238000003379 elimination reaction Methods 0.000 description 8
239000012535 impurity Substances 0.000 description 8
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 8
239000012265 solid product Substances 0.000 description 8
OSVHLUXLWQLPIY-KBAYOESNSA-N butyl 2-[(6aR,9R,10aR)-1-hydroxy-9-(hydroxymethyl)-6,6-dimethyl-6a,7,8,9,10,10a-hexahydrobenzo[c]chromen-3-yl]-2-methylpropanoate Chemical compound C(CCC)OC(C(C)(C)C1=CC(=C2[C@H]3[C@H](C(OC2=C1)(C)C)CC[C@H](C3)CO)O)=O OSVHLUXLWQLPIY-KBAYOESNSA-N 0.000 description 7
239000003153 chemical reaction reagent Substances 0.000 description 7
238000010511 deprotection reaction Methods 0.000 description 7
210000003739 neck Anatomy 0.000 description 7
229910052757 nitrogen Inorganic materials 0.000 description 7
239000000725 suspension Substances 0.000 description 7
ILMRJRBKQSSXGY-UHFFFAOYSA-N tert-butyl(dimethyl)silicon Chemical compound C[Si](C)C(C)(C)C ILMRJRBKQSSXGY-UHFFFAOYSA-N 0.000 description 7
229940086542 triethylamine Drugs 0.000 description 7
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 6
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 6
238000004458 analytical method Methods 0.000 description 6
239000012038 nucleophile Substances 0.000 description 6
238000005935 nucleophilic addition reaction Methods 0.000 description 6
238000001953 recrystallisation Methods 0.000 description 6
230000003637 steroidlike Effects 0.000 description 6
VIMMECPCYZXUCI-MIMFYIINSA-N (4s,6r)-6-[(1e)-4,4-bis(4-fluorophenyl)-3-(1-methyltetrazol-5-yl)buta-1,3-dienyl]-4-hydroxyoxan-2-one Chemical compound CN1N=NN=C1C(\C=C\[C@@H]1OC(=O)C[C@@H](O)C1)=C(C=1C=CC(F)=CC=1)C1=CC=C(F)C=C1 VIMMECPCYZXUCI-MIMFYIINSA-N 0.000 description 5
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
229910052799 carbon Inorganic materials 0.000 description 5
239000000356 contaminant Substances 0.000 description 5
238000002425 crystallisation Methods 0.000 description 5
230000008025 crystallization Effects 0.000 description 5
229910052739 hydrogen Inorganic materials 0.000 description 5
125000001424 substituent group Chemical group 0.000 description 5
BCNZYOJHNLTNEZ-UHFFFAOYSA-N tert-butyldimethylsilyl chloride Chemical compound CC(C)(C)[Si](C)(C)Cl BCNZYOJHNLTNEZ-UHFFFAOYSA-N 0.000 description 5
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 4
230000010933 acylation Effects 0.000 description 4
238000005917 acylation reaction Methods 0.000 description 4
238000013019 agitation Methods 0.000 description 4
238000005859 coupling reaction Methods 0.000 description 4
239000012039 electrophile Substances 0.000 description 4
239000001257 hydrogen Substances 0.000 description 4
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
239000011777 magnesium Substances 0.000 description 4
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
239000012044 organic layer Substances 0.000 description 4
239000011734 sodium Substances 0.000 description 4
BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 description 4
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 3
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 3
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 3
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 3
230000021736 acetylation Effects 0.000 description 3
238000006640 acetylation reaction Methods 0.000 description 3
238000004440 column chromatography Methods 0.000 description 3
125000004122 cyclic group Chemical group 0.000 description 3
125000005842 heteroatom Chemical group 0.000 description 3
125000001183 hydrocarbyl group Chemical group 0.000 description 3
125000002887 hydroxy group Chemical group [H]O* 0.000 description 3
229910052744 lithium Inorganic materials 0.000 description 3
238000007344 nucleophilic reaction Methods 0.000 description 3
230000000737 periodic effect Effects 0.000 description 3
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 3
MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 3
239000000126 substance Substances 0.000 description 3
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 3
YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 description 2
NYPYPOZNGOXYSU-UHFFFAOYSA-N 3-bromopyridine Chemical compound BrC1=CC=CN=C1 NYPYPOZNGOXYSU-UHFFFAOYSA-N 0.000 description 2
229960000549 4-dimethylaminophenol Drugs 0.000 description 2
238000006418 Brown reaction Methods 0.000 description 2
239000004215 Carbon black (E152) Substances 0.000 description 2
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 2
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 2
FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 description 2
239000012346 acetyl chloride Substances 0.000 description 2
239000008186 active pharmaceutical agent Substances 0.000 description 2
239000007864 aqueous solution Substances 0.000 description 2
125000004429 atom Chemical group 0.000 description 2
SRSXLGNVWSONIS-UHFFFAOYSA-M benzenesulfonate Chemical compound [O-]S(=O)(=O)C1=CC=CC=C1 SRSXLGNVWSONIS-UHFFFAOYSA-M 0.000 description 2
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 2
239000011575 calcium Substances 0.000 description 2
239000003054 catalyst Substances 0.000 description 2
230000001276 controlling effect Effects 0.000 description 2
239000010949 copper Substances 0.000 description 2
VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical compound [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 description 2
150000002148 esters Chemical class 0.000 description 2
UQSQSQZYBQSBJZ-UHFFFAOYSA-M fluorosulfonate Chemical compound [O-]S(F)(=O)=O UQSQSQZYBQSBJZ-UHFFFAOYSA-M 0.000 description 2
125000000524 functional group Chemical group 0.000 description 2
125000000623 heterocyclic group Chemical group 0.000 description 2
229930195733 hydrocarbon Natural products 0.000 description 2
150000002430 hydrocarbons Chemical class 0.000 description 2
239000010410 layer Substances 0.000 description 2
ANYSGBYRTLOUPO-UHFFFAOYSA-N lithium tetramethylpiperidide Chemical compound [Li]N1C(C)(C)CCCC1(C)C ANYSGBYRTLOUPO-UHFFFAOYSA-N 0.000 description 2
JDOZOOBCADNBIJ-UHFFFAOYSA-N lithium;2h-pyridin-2-ide Chemical compound [Li+].C1=CC=N[C-]=C1 JDOZOOBCADNBIJ-UHFFFAOYSA-N 0.000 description 2
CWJCFOZDFPMHBR-UHFFFAOYSA-N lithium;3h-pyridin-3-ide Chemical compound [Li+].C1=C[C-]=CN=C1 CWJCFOZDFPMHBR-UHFFFAOYSA-N 0.000 description 2
229910052749 magnesium Inorganic materials 0.000 description 2
229910052751 metal Inorganic materials 0.000 description 2
239000002184 metal Substances 0.000 description 2
NSPJNIDYTSSIIY-UHFFFAOYSA-N methoxy(methoxymethoxy)methane Chemical compound COCOCOC NSPJNIDYTSSIIY-UHFFFAOYSA-N 0.000 description 2
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
230000000269 nucleophilic effect Effects 0.000 description 2
239000003960 organic solvent Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
239000011591 potassium Substances 0.000 description 2
IUBQJLUDMLPAGT-UHFFFAOYSA-N potassium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([K])[Si](C)(C)C IUBQJLUDMLPAGT-UHFFFAOYSA-N 0.000 description 2
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 2
239000000047 product Substances 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 2
239000011877 solvent mixture Substances 0.000 description 2
FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 2
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 description 2
125000000025 triisopropylsilyl group Chemical group C(C)(C)[Si](C(C)C)(C(C)C)* 0.000 description 2
238000001665 trituration Methods 0.000 description 2
125000004169 (C1-C6) alkyl group Chemical group 0.000 description 1
125000005918 1,2-dimethylbutyl group Chemical group 0.000 description 1
125000004206 2,2,2-trifluoroethyl group Chemical group [H]C([H])(*)C(F)(F)F 0.000 description 1
125000006176 2-ethylbutyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(C([H])([H])*)C([H])([H])C([H])([H])[H] 0.000 description 1
125000005916 2-methylpentyl group Chemical group 0.000 description 1
125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 description 1
BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
125000003542 3-methylbutan-2-yl group Chemical group [H]C([H])([H])C([H])(*)C([H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000005917 3-methylpentyl group Chemical group 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
125000005915 C6-C14 aryl group Chemical group 0.000 description 1
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 1
RYGMFSIKBFXOCR-UHFFFAOYSA-N Copper Chemical compound [Cu] RYGMFSIKBFXOCR-UHFFFAOYSA-N 0.000 description 1
239000002841 Lewis acid Substances 0.000 description 1
ZDZOTLJHXYCWBA-VCVYQWHSSA-N N-debenzoyl-N-(tert-butoxycarbonyl)-10-deacetyltaxol Chemical compound O([C@H]1[C@H]2[C@@](C([C@H](O)C3=C(C)[C@@H](OC(=O)[C@H](O)[C@@H](NC(=O)OC(C)(C)C)C=4C=CC=CC=4)C[C@]1(O)C3(C)C)=O)(C)[C@@H](O)C[C@H]1OC[C@]12OC(=O)C)C(=O)C1=CC=CC=C1 ZDZOTLJHXYCWBA-VCVYQWHSSA-N 0.000 description 1
108091006629 SLC13A2 Proteins 0.000 description 1
BQCADISMDOOEFD-UHFFFAOYSA-N Silver Chemical compound [Ag] BQCADISMDOOEFD-UHFFFAOYSA-N 0.000 description 1
NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 1
NJXLIOOJACLKHV-UHFFFAOYSA-M [Br-].[Mg+]C1=CC=CN=C1 Chemical compound [Br-].[Mg+]C1=CC=CN=C1 NJXLIOOJACLKHV-UHFFFAOYSA-M 0.000 description 1
KPCZJLGGXRGYIE-UHFFFAOYSA-N [C]1=CC=CN=C1 Chemical group [C]1=CC=CN=C1 KPCZJLGGXRGYIE-UHFFFAOYSA-N 0.000 description 1
KHHUWSREFUHHDL-UHFFFAOYSA-N [Mg]C1=CC=CC=N1 Chemical compound [Mg]C1=CC=CC=N1 KHHUWSREFUHHDL-UHFFFAOYSA-N 0.000 description 1
GHASBQYLQLMSOZ-UHFFFAOYSA-N [Zn]C1=CC=CC=N1 Chemical compound [Zn]C1=CC=CC=N1 GHASBQYLQLMSOZ-UHFFFAOYSA-N 0.000 description 1
229960000853 abiraterone Drugs 0.000 description 1
GZOSMCIZMLWJML-VJLLXTKPSA-N abiraterone Chemical compound C([C@H]1[C@H]2[C@@H]([C@]3(CC[C@H](O)CC3=CC2)C)CC[C@@]11C)C=C1C1=CC=CN=C1 GZOSMCIZMLWJML-VJLLXTKPSA-N 0.000 description 1
150000007513 acids Chemical class 0.000 description 1
230000006978 adaptation Effects 0.000 description 1
125000003342 alkenyl group Chemical group 0.000 description 1
125000000304 alkynyl group Chemical group 0.000 description 1
125000002178 anthracenyl group Chemical group C1(=CC=CC2=CC3=CC=CC=C3C=C12)* 0.000 description 1
229910052788 barium Inorganic materials 0.000 description 1
DSAJWYNOEDNPEQ-UHFFFAOYSA-N barium atom Chemical compound [Ba] DSAJWYNOEDNPEQ-UHFFFAOYSA-N 0.000 description 1
230000008901 benefit Effects 0.000 description 1
125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
229910052790 beryllium Inorganic materials 0.000 description 1
ATBAMAFKBVZNFJ-UHFFFAOYSA-N beryllium atom Chemical compound [Be] ATBAMAFKBVZNFJ-UHFFFAOYSA-N 0.000 description 1
238000009835 boiling Methods 0.000 description 1
UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical class B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 description 1
229910000085 borane Inorganic materials 0.000 description 1
239000012267 brine Substances 0.000 description 1
150000007516 brønsted-lowry acids Chemical class 0.000 description 1
239000006227 byproduct Substances 0.000 description 1
229910052793 cadmium Inorganic materials 0.000 description 1
BDOSMKKIYDKNTQ-UHFFFAOYSA-N cadmium atom Chemical compound [Cd] BDOSMKKIYDKNTQ-UHFFFAOYSA-N 0.000 description 1
229910052792 caesium Inorganic materials 0.000 description 1
TVFDJXOCXUVLDH-UHFFFAOYSA-N caesium atom Chemical compound [Cs] TVFDJXOCXUVLDH-UHFFFAOYSA-N 0.000 description 1
229910052791 calcium Inorganic materials 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
238000002512 chemotherapy Methods 0.000 description 1
238000011097 chromatography purification Methods 0.000 description 1
229910052802 copper Inorganic materials 0.000 description 1
230000002596 correlated effect Effects 0.000 description 1
238000006880 cross-coupling reaction Methods 0.000 description 1
239000013078 crystal Substances 0.000 description 1
125000000392 cycloalkenyl group Chemical group 0.000 description 1
125000000753 cycloalkyl group Chemical group 0.000 description 1
BGTOWKSIORTVQH-HOSYLAQJSA-N cyclopentanone Chemical group O=[13C]1CCCC1 BGTOWKSIORTVQH-HOSYLAQJSA-N 0.000 description 1
230000018044 dehydration Effects 0.000 description 1
FMGSKLZLMKYGDP-USOAJAOKSA-N dehydroepiandrosterone Chemical compound C1[C@@H](O)CC[C@]2(C)[C@H]3CC[C@](C)(C(CC4)=O)[C@@H]4[C@@H]3CC=C21 FMGSKLZLMKYGDP-USOAJAOKSA-N 0.000 description 1
238000004090 dissolution Methods 0.000 description 1
229960003668 docetaxel Drugs 0.000 description 1
230000008030 elimination Effects 0.000 description 1
125000001033 ether group Chemical group 0.000 description 1
125000005448 ethoxyethyl group Chemical group [H]C([H])([H])C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
238000001704 evaporation Methods 0.000 description 1
230000008020 evaporation Effects 0.000 description 1
238000000605 extraction Methods 0.000 description 1
239000000706 filtrate Substances 0.000 description 1
239000012467 final product Substances 0.000 description 1
239000012634 fragment Substances 0.000 description 1
125000001188 haloalkyl group Chemical group 0.000 description 1
150000002431 hydrogen Chemical class 0.000 description 1
125000002883 imidazolyl group Chemical group 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
150000002500 ions Chemical class 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
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
238000011031 large-scale manufacturing process Methods 0.000 description 1
150000007517 lewis acids Chemical class 0.000 description 1
229910052943 magnesium sulfate Inorganic materials 0.000 description 1
235000019341 magnesium sulphate Nutrition 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
QSHDDOUJBYECFT-UHFFFAOYSA-N mercury Chemical compound [Hg] QSHDDOUJBYECFT-UHFFFAOYSA-N 0.000 description 1
229910052753 mercury Inorganic materials 0.000 description 1
150000002739 metals Chemical class 0.000 description 1
230000001394 metastastic effect Effects 0.000 description 1
206010061289 metastatic neoplasm Diseases 0.000 description 1
KSBCPTHITUHSPO-UHFFFAOYSA-N methyl 3-hydroxy-4-methoxy-10-nitrophenanthrene-1-carboxylate Chemical compound COC(=O)C1=CC(=C(C=2C3=CC=CC=C3C=C(C1=2)[N+](=O)[O-])OC)O KSBCPTHITUHSPO-UHFFFAOYSA-N 0.000 description 1
230000004048 modification Effects 0.000 description 1
238000012986 modification Methods 0.000 description 1
PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 1
125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001280 n-hexyl group Chemical group C(CCCCC)* 0.000 description 1
125000000740 n-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
125000001624 naphthyl group Chemical group 0.000 description 1
239000012299 nitrogen atmosphere Substances 0.000 description 1
238000005457 optimization Methods 0.000 description 1
125000002971 oxazolyl group Chemical group 0.000 description 1
229910052763 palladium Inorganic materials 0.000 description 1
125000001792 phenanthrenyl group Chemical group C1(=CC=CC=2C3=CC=CC=C3C=CC12)* 0.000 description 1
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 1
ANRQGKOBLBYXFM-UHFFFAOYSA-M phenylmagnesium bromide Chemical compound Br[Mg]C1=CC=CC=C1 ANRQGKOBLBYXFM-UHFFFAOYSA-M 0.000 description 1
238000001556 precipitation Methods 0.000 description 1
XOFYZVNMUHMLCC-ZPOLXVRWSA-N prednisone Chemical compound O=C1C=C[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 XOFYZVNMUHMLCC-ZPOLXVRWSA-N 0.000 description 1
229960004618 prednisone Drugs 0.000 description 1
125000003373 pyrazinyl group Chemical group 0.000 description 1
125000003226 pyrazolyl group Chemical group 0.000 description 1
GRJJQCWNZGRKAU-UHFFFAOYSA-N pyridin-1-ium;fluoride Chemical compound F.C1=CC=NC=C1 GRJJQCWNZGRKAU-UHFFFAOYSA-N 0.000 description 1
238000010791 quenching Methods 0.000 description 1
239000000376 reactant Substances 0.000 description 1
238000010992 reflux Methods 0.000 description 1
229910052701 rubidium Inorganic materials 0.000 description 1
IGLNJRXAVVLDKE-UHFFFAOYSA-N rubidium atom Chemical compound [Rb] IGLNJRXAVVLDKE-UHFFFAOYSA-N 0.000 description 1
229930195734 saturated hydrocarbon Natural products 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
125000003548 sec-pentyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
239000000741 silica gel Substances 0.000 description 1
229910002027 silica gel Inorganic materials 0.000 description 1
229910052709 silver Inorganic materials 0.000 description 1
239000004332 silver Substances 0.000 description 1
235000017557 sodium bicarbonate Nutrition 0.000 description 1
229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
PUZPDOWCWNUUKD-UHFFFAOYSA-M sodium fluoride Chemical group [F-].[Na+] PUZPDOWCWNUUKD-UHFFFAOYSA-M 0.000 description 1
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 1
229910052712 strontium Inorganic materials 0.000 description 1
CIOAGBVUUVVLOB-UHFFFAOYSA-N strontium atom Chemical compound [Sr] CIOAGBVUUVVLOB-UHFFFAOYSA-N 0.000 description 1
150000003871 sulfonates Chemical class 0.000 description 1
229910052717 sulfur Inorganic materials 0.000 description 1
239000011593 sulfur Substances 0.000 description 1
235000011149 sulphuric acid Nutrition 0.000 description 1
238000003786 synthesis reaction Methods 0.000 description 1
JBQYATWDVHIOAR-UHFFFAOYSA-N tellanylidenegermanium Chemical compound [Te]=[Ge] JBQYATWDVHIOAR-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
125000001973 tert-pentyl group Chemical group [H]C([H])([H])C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
125000001544 thienyl group Chemical group 0.000 description 1
231100000331 toxic Toxicity 0.000 description 1
230000002588 toxic effect Effects 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

Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J51/00—Normal steroids with unmodified cyclopenta(a)hydrophenanthrene skeleton not provided for in groups C07J1/00 - C07J43/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J43/00—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton
- C07J43/003—Normal steroids having a nitrogen-containing hetero ring spiro-condensed or not condensed with the cyclopenta(a)hydrophenanthrene skeleton not condensed
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07J—STEROIDS
- C07J1/00—Normal steroids containing carbon, hydrogen, halogen or oxygen, not substituted in position 17 beta by a carbon atom, e.g. estrane, androstane
- C07J1/0003—Androstane derivatives
- C07J1/0011—Androstane derivatives substituted in position 17 by a keto group

Landscapes

Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Steroid Compounds (AREA)

CA2871314A 2012-04-23 2013-04-22 Procede de preparation de steroides 17-substitues Abandoned CA2871314A1 (fr)

Applications Claiming Priority (5)

Application Number	Priority Date	Filing Date	Title
US201261637048P	2012-04-23	2012-04-23
US61/637,048		2012-04-23
US201261642253P	2012-05-03	2012-05-03
US61/642,253		2012-05-03
PCT/CA2013/050311 WO2013159225A1 (fr)	2012-04-23	2013-04-22	Procédé de préparation de stéroïdes 17-substitués

Publications (1)

Publication Number	Publication Date
CA2871314A1 true CA2871314A1 (fr)	2013-10-31

Family

ID=49482082

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
CA2871314A Abandoned CA2871314A1 (fr)	2012-04-23	2013-04-22	Procede de preparation de steroides 17-substitues

Country Status (3)

Country	Link
EP (1)	EP2841444A4 (fr)
CA (1)	CA2871314A1 (fr)
WO (1)	WO2013159225A1 (fr)

Families Citing this family (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
WO2014016830A1 (fr) *	2012-07-25	2014-01-30	Mapi Pharma Ltd.	Procédé et intermédiaires utilisés pour la préparation de l'acétate d'abiratérone
US9937259B2 (en) *	2014-06-27	2018-04-10	Zhuhai Beihai Biotech Co., Ltd.	Abiraterone derivatives and non-covalent complexes with albumin
US10722527B2 (en)	2015-04-10	2020-07-28	Capsugel Belgium Nv	Abiraterone acetate lipid formulations
CN105503992A (zh) *	2016-01-22	2016-04-20	江苏联环药业股份有限公司	一种醋酸阿比特龙的制备方法
CN107722101A (zh) *	2017-11-03	2018-02-23	郑州大学	甾体吡啶类衍生物及其制备方法和应用
US10792292B2 (en)	2019-03-06	2020-10-06	Propella Therapeutics, Inc.	Abiraterone prodrugs
US11957696B2 (en)	2021-02-15	2024-04-16	Propella Therapeutics, Inc.	Abiraterone prodrugs
CN117683073A (zh) *	2023-12-15	2024-03-12	江苏希迪制药有限公司	醋酸阿比特龙的合成方法

Family Cites Families (8)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US2938030A (en) *	1956-10-03	1960-05-24	Ciba Pharm Prod Inc	New steroids substituted by a heterocyclic nitrogen-containing ring in 17-position
CA2132449C (fr) *	1992-03-31	2002-09-10	Susan E. Barrie	Steroides 17-substitues utilises dans le traitement du cancer
AU676088B2 (en) *	1993-09-30	1997-02-27	British Technology Group Limited	Synthesis of 17-(3-pyridyl) steroids
CN101768199B (zh) *	2009-12-24	2014-03-26	深圳万乐药业有限公司	醋酸阿比特龙的多晶型物及其制备方法
CN102321142A (zh) *	2011-09-29	2012-01-18	重庆医药工业研究院有限责任公司	一种醋酸阿比特龙晶型及其制备方法
EP2607371A1 (fr) *	2011-12-23	2013-06-26	Crystal Pharma, S.A.U.	Procédés de préparation d'abiratérone et composés associés
WO2014016830A1 (fr) *	2012-07-25	2014-01-30	Mapi Pharma Ltd.	Procédé et intermédiaires utilisés pour la préparation de l'acétate d'abiratérone
CN102898495B (zh) *	2012-11-12	2014-11-26	浙江神洲药业有限公司	醋酸阿比特龙酯的制备方法

2013
- 2013-04-22 EP EP13780667.5A patent/EP2841444A4/fr not_active Withdrawn
- 2013-04-22 CA CA2871314A patent/CA2871314A1/fr not_active Abandoned
- 2013-04-22 WO PCT/CA2013/050311 patent/WO2013159225A1/fr not_active Ceased

Also Published As

Publication number	Publication date
EP2841444A1 (fr)	2015-03-04
WO2013159225A1 (fr)	2013-10-31
EP2841444A4 (fr)	2015-11-04

Legal Events

Date	Code	Title	Description
2019-06-04	FZDE	Discontinued	Effective date: 20190423

Publication	Publication Date	Title
CA2871314A1 (fr)	2013-10-31	Procede de preparation de steroides 17-substitues
ES2624667T3 (es)	2017-07-17	Procedimiento para la preparación de estetrol
JP3722835B2 (ja)	2005-11-30	１７−（３−ピリジル）ステロイドの合成
CA2851330C (fr)	2019-07-16	Procede de preparation de steroides 17-substitues
EP0312867B1 (fr)	1992-05-06	Dérivés d'acides biliaires, procédé pour leur préparation et compositions pharmaceutiques les contenant
CA2859897A1 (fr)	2013-03-07	Synthese d'abiraterone et de composes associes
US10273263B2 (en)	2019-04-30	Pro-drug forming compounds
BR112013030833B1 (pt)	2019-09-03	processo para a preparação de um composto de fórmula (i) e processo para a preparação de estetrol
US20160237109A1 (en)	2016-08-18	Method for Preparing Abiraterone Acetate
CN107383137A (zh)	2017-11-24	一种鹅去氧胆酸的合成方法
WO2020155613A1 (fr)	2020-08-06	Procédé de préparation de composé d'ectéinascidine et d'un intermédiaire de celui-ci
CN103788164A (zh)	2014-05-14	一种氟维司群的制备方法
AU775831B2 (en)	2004-08-19	Process for preparing 17alpha-acetoxy-11beta-(4-N,N-(dimethylamino)phenyl)-21- methoxy-19-norpregna-4,9-diene-3,20-dione, intermediates useful in the process, and processes for preparing such intermediates
JP6904519B2 (ja)	2021-07-14	抗腫瘍薬物ニラパリブの中間体を合成するための製造方法および中間体
CN110804082A (zh)	2020-02-18	一种胆酸类衍生物及其制备方法和应用
CN102964414A (zh)	2013-03-13	17位甾体羧酸酯的合成方法
ES2581317T3 (es)	2016-09-05	Proceso de preparación de abiraterona o acetato de abiraterona
EP2917225A1 (fr)	2015-09-16	Procédé de fabrication de 3-acétate d'abiratérone
WO2014071983A1 (fr)	2014-05-15	Processus de fabrication de l'intermédiaire 17-triflate d'abiratérone-3-acétate
JPS6118559B2 (fr)	1986-05-13