JP2021512168A - 有機化合物の塩形態 - Google Patents
有機化合物の塩形態 Download PDFInfo
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- JP2021512168A JP2021512168A JP2020562105A JP2020562105A JP2021512168A JP 2021512168 A JP2021512168 A JP 2021512168A JP 2020562105 A JP2020562105 A JP 2020562105A JP 2020562105 A JP2020562105 A JP 2020562105A JP 2021512168 A JP2021512168 A JP 2021512168A
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- Prior art keywords
- salt
- organic solvent
- salt compound
- derived
- solvent
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- 150000003839 salts Chemical group 0.000 title claims abstract description 74
- 150000002894 organic compounds Chemical class 0.000 title description 2
- 238000000034 method Methods 0.000 claims abstract description 30
- -1 salt compound Chemical class 0.000 claims abstract description 25
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 63
- 239000002904 solvent Substances 0.000 claims description 56
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 42
- ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 claims description 38
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 36
- 239000002253 acid Substances 0.000 claims description 34
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 31
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 claims description 24
- 239000003960 organic solvent Substances 0.000 claims description 19
- 239000000203 mixture Substances 0.000 claims description 17
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 claims description 15
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 15
- QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical class N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 claims description 14
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 12
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 claims description 12
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 11
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 claims description 11
- 239000003495 polar organic solvent Substances 0.000 claims description 11
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 9
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 9
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 9
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 claims description 9
- 150000001875 compounds Chemical class 0.000 claims description 9
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 9
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 8
- 229910021529 ammonia Inorganic materials 0.000 claims description 7
- UEGPKNKPLBYCNK-UHFFFAOYSA-L magnesium acetate Chemical compound [Mg+2].CC([O-])=O.CC([O-])=O UEGPKNKPLBYCNK-UHFFFAOYSA-L 0.000 claims description 7
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 7
- IKXCHOUDIPZROZ-LXGUWJNJSA-N (2r,3r,4r,5s)-6-(ethylamino)hexane-1,2,3,4,5-pentol Chemical compound CCNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO IKXCHOUDIPZROZ-LXGUWJNJSA-N 0.000 claims description 6
- SPEUIVXLLWOEMJ-UHFFFAOYSA-N 1,1-dimethoxyethane Chemical group COC(C)OC SPEUIVXLLWOEMJ-UHFFFAOYSA-N 0.000 claims description 6
- KKFDCBRMNNSAAW-UHFFFAOYSA-N 2-(morpholin-4-yl)ethanol Chemical compound OCCN1CCOCC1 KKFDCBRMNNSAAW-UHFFFAOYSA-N 0.000 claims description 6
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 6
- MBBZMMPHUWSWHV-BDVNFPICSA-N N-methylglucamine Chemical compound CNC[C@H](O)[C@@H](O)[C@H](O)[C@H](O)CO MBBZMMPHUWSWHV-BDVNFPICSA-N 0.000 claims description 6
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 6
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 6
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 claims description 6
- JUHORIMYRDESRB-UHFFFAOYSA-N benzathine Chemical compound C=1C=CC=CC=1CNCCNCC1=CC=CC=C1 JUHORIMYRDESRB-UHFFFAOYSA-N 0.000 claims description 6
- OEYIOHPDSNJKLS-UHFFFAOYSA-N choline Chemical compound C[N+](C)(C)CCO OEYIOHPDSNJKLS-UHFFFAOYSA-N 0.000 claims description 6
- 229960001231 choline Drugs 0.000 claims description 6
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 6
- 239000011654 magnesium acetate Substances 0.000 claims description 6
- 229940069446 magnesium acetate Drugs 0.000 claims description 6
- 235000011285 magnesium acetate Nutrition 0.000 claims description 6
- LENZDBCJOHFCAS-UHFFFAOYSA-N tris Chemical compound OCC(N)(CO)CO LENZDBCJOHFCAS-UHFFFAOYSA-N 0.000 claims description 6
- 229960000281 trometamol Drugs 0.000 claims description 6
- NPYPAHLBTDXSSS-UHFFFAOYSA-N Potassium ion Chemical compound [K+] NPYPAHLBTDXSSS-UHFFFAOYSA-N 0.000 claims description 5
- FKNQFGJONOIPTF-UHFFFAOYSA-N Sodium cation Chemical compound [Na+] FKNQFGJONOIPTF-UHFFFAOYSA-N 0.000 claims description 5
- UPABQMWFWCMOFV-UHFFFAOYSA-N benethamine Chemical compound C=1C=CC=CC=1CNCCC1=CC=CC=C1 UPABQMWFWCMOFV-UHFFFAOYSA-N 0.000 claims description 5
- 150000001768 cations Chemical class 0.000 claims description 5
- 229940125782 compound 2 Drugs 0.000 claims description 5
- 229910001414 potassium ion Inorganic materials 0.000 claims description 5
- 229910001415 sodium ion Inorganic materials 0.000 claims description 5
- 239000012453 solvate Substances 0.000 claims description 5
- BFSVOASYOCHEOV-UHFFFAOYSA-N 2-diethylaminoethanol Chemical compound CCN(CC)CCO BFSVOASYOCHEOV-UHFFFAOYSA-N 0.000 claims description 4
- UEEJHVSXFDXPFK-UHFFFAOYSA-N N-dimethylaminoethanol Chemical compound CN(C)CCO UEEJHVSXFDXPFK-UHFFFAOYSA-N 0.000 claims description 4
- RWGFKTVRMDUZSP-UHFFFAOYSA-N cumene Chemical compound CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 claims description 4
- 125000001664 diethylamino group Chemical group [H]C([H])([H])C([H])([H])N(*)C([H])([H])C([H])([H])[H] 0.000 claims description 4
- XBRDBODLCHKXHI-UHFFFAOYSA-N epolamine Chemical compound OCCN1CCCC1 XBRDBODLCHKXHI-UHFFFAOYSA-N 0.000 claims description 4
- WPLOVIFNBMNBPD-ATHMIXSHSA-N subtilin Chemical compound CC1SCC(NC2=O)C(=O)NC(CC(N)=O)C(=O)NC(C(=O)NC(CCCCN)C(=O)NC(C(C)CC)C(=O)NC(=C)C(=O)NC(CCCCN)C(O)=O)CSC(C)C2NC(=O)C(CC(C)C)NC(=O)C1NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(NC(=O)C1NC(=O)C(=C/C)/NC(=O)C(CCC(N)=O)NC(=O)C(CC(C)C)NC(=O)C(C)NC(=O)CNC(=O)C(NC(=O)C(NC(=O)C2NC(=O)CNC(=O)C3CCCN3C(=O)C(NC(=O)C3NC(=O)C(CC(C)C)NC(=O)C(=C)NC(=O)C(CCC(O)=O)NC(=O)C(NC(=O)C(CCCCN)NC(=O)C(N)CC=4C5=CC=CC=C5NC=4)CSC3)C(C)SC2)C(C)C)C(C)SC1)CC1=CC=CC=C1 WPLOVIFNBMNBPD-ATHMIXSHSA-N 0.000 claims description 4
- WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 claims description 3
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 3
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 claims description 3
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 3
- 229910001424 calcium ion Inorganic materials 0.000 claims description 3
- GJRQTCIYDGXPES-UHFFFAOYSA-N iso-butyl acetate Natural products CC(C)COC(C)=O GJRQTCIYDGXPES-UHFFFAOYSA-N 0.000 claims description 3
- FGKJLKRYENPLQH-UHFFFAOYSA-M isocaproate Chemical compound CC(C)CCC([O-])=O FGKJLKRYENPLQH-UHFFFAOYSA-M 0.000 claims description 3
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 claims description 3
- 229940011051 isopropyl acetate Drugs 0.000 claims description 3
- OQAGVSWESNCJJT-UHFFFAOYSA-N isovaleric acid methyl ester Natural products COC(=O)CC(C)C OQAGVSWESNCJJT-UHFFFAOYSA-N 0.000 claims description 3
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 claims description 3
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 3
- 239000002244 precipitate Substances 0.000 claims description 3
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 3
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 3
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- 150000001412 amines Chemical group 0.000 claims description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 31
- 239000002552 dosage form Substances 0.000 abstract description 4
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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 9
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- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
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- 150000007513 acids Chemical class 0.000 description 1
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- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
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- DQYBDCGIPTYXML-UHFFFAOYSA-N ethoxyethane;hydrate Chemical compound O.CCOCC DQYBDCGIPTYXML-UHFFFAOYSA-N 0.000 description 1
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- 239000000395 magnesium oxide Substances 0.000 description 1
- CPLXHLVBOLITMK-UHFFFAOYSA-N magnesium oxide Inorganic materials [Mg]=O CPLXHLVBOLITMK-UHFFFAOYSA-N 0.000 description 1
- AXZKOIWUVFPNLO-UHFFFAOYSA-N magnesium;oxygen(2-) Chemical compound [O-2].[Mg+2] AXZKOIWUVFPNLO-UHFFFAOYSA-N 0.000 description 1
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- 102000006240 membrane receptors Human genes 0.000 description 1
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- 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
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- 229960004023 minocycline Drugs 0.000 description 1
- BAVYZALUXZFZLV-UHFFFAOYSA-N mono-methylamine Natural products NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 1
- 230000002107 myocardial effect Effects 0.000 description 1
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- 210000003463 organelle Anatomy 0.000 description 1
- GSWAOPJLTADLTN-UHFFFAOYSA-N oxidanimine Chemical compound [O-][NH3+] GSWAOPJLTADLTN-UHFFFAOYSA-N 0.000 description 1
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Images
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D231/38—Nitrogen atoms
- C07D231/40—Acylated on said nitrogen atom
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
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- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
- A61K31/415—1,2-Diazoles
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- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
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Abstract
Description
[nは1、2、または3であり、
mは0から3までの、非整数であってもよく、mは通常0、0.5、1、2、または3であり、
「Sol」は溶媒分子であり、例えば、水またはC2〜C4のアルコールであってもよく、
X+は陽イオンであり、例えば、カリウムイオン、ナトリウムイオン、カルシウムイオン、マグネシウムイオン、アンモニウムイオンまたは置換アンモニウムイオンであってもよい。]を有する塩化合物。
塩のスクリーニングは、実験ごとに3種の溶媒および22種の塩基と約25mgの化合物1(KM−819)を使用して行われ、1:1.1(遊離酸:塩基)の比率で添加された。調製後、濾過およびXRPDによる分析の前に、試料を5日間静置させた。塩が完全に溶媒に可溶性のままである場合には、溶媒を試料からゆっくりと蒸発させた。
mは0から3までの、例えば0.5や1.5などの非整数であってもよく、
「Sol」は溶媒分子であり、例えば、水またはC2〜C4アルコールであってもよく、
X+は陽イオンであり、例えば、カリウムイオン、ナトリウムイオン、カルシウムイオン、マグネシウムイオン、アンモニウムイオンまたは置換されたアンモニウムイオンであってもよい。
nは1、2、または3であり、
mは0から3であり、
X+は陽イオンであり、
「Sol」は溶媒分子である。]を有する塩化合物を調製する方法であって、
i)有機溶媒または水と混合した有機溶媒に式2の化合物の遊離酸の形態を溶解すること;
ii)式2の遊離酸化合物を滴定するのに必要な化学量論量を超えた塩基を、過剰に添加して、式2の塩化合物の沈殿物を形成すること;および
iii)沈殿物を集めて塩化合物2を得ること
を含む、方法も開示される。
本開示の塩化合物を調製するための一般的な方法は、以下のスキームに例示される。
40μLアルミ製皿(ベント付き)を使用したPerkin Elmer PYRIS 1 DSC。データ収集および分析はPerkin Elmerの制御および分析ソフトウェア、バージョン11.0.2.0468を使用して行った。
パターン1:結晶性ナトリウム塩(試験した溶媒の大部分から)
パターン2:ナトリウム塩の溶媒和物(2−ブタノールおよび2−プロパノールから)
パターン3:起こり得る新しい多形(4−メチルペンタン−2−オンから)
パターン4:不明な汚染物を含んだナトリウム塩(アセトンから)
パターン5:ナトリウム塩のヘミエタノエート(エタノールから)。
Claims (19)
- X+がカリウムイオン、ナトリウムイオン、カルシウムイオン、または置換されたアンモニア分子である、請求項1に記載の塩化合物。
- X+が、コリン、ジエチルアミン、ジメチルアミン、L−リシン、N、N’−ジベンジルエチレンジアミン、N−エチルグルカミン、1−(2−ヒドロキシエチル)ピロリジン、N−(フェニルメチル)ベンゼンエタンアミン、アンモニア、酢酸マグネシウム、N−メチルグルカミン、トロメタミン、4−(2−ヒドロキシエチル)モルホリン、2−(ジエチルアミノ)エタノール、2−ジメチルアミノエタノールから成る群から選択される第四級アミンである、請求項1に記載の塩化合物。
- X+がカリウムイオン、ナトリウムイオン、または第四級ジメチルアミンまたは第四級ジエチルアミンである、請求項1に記載の塩化合物。
- mが0.5または1である、請求項1に記載の塩化合物。
- mが0.5または1である、請求項4に記載の塩化合物。
- 4−メチル−ペンタン−2−オン、エタノールまたはジイソプロピルエーテルをさらに含有する溶媒和物である、請求項1に記載の塩化合物。
- エタノールまたはジイソプロピルエーテルをさらに含有する溶媒和物である、請求項4に記載の塩化合物。
- 前記有機溶媒が、1,1−ジメトキシエタン、アセトニトリル、エタノール、1,2−ジクロロエタン、ベンゾニトリル、酢酸エチル、1,4−ジオキサン、アニソール、ヘプタン、2−ブタノール、クメン、ヘキサン、2−プロパノール、シクロヘキサン、酢酸イソプロピル、4−メチルペンタン−2−オン、ジクロロメタン、メタノール、アセトン、ジイソプロピルエーテル(DIPE)、酢酸イソブチル、テトラリン、トルエン、メチルエチルケトン(MEK)、N−メチルピロリドン、tert−ブチルメチルエーテル(TMBE)、ニトロメタン、ピリジンまたはテトラヒドロフラン、またはそれらの2種または3種のいずれかの混合物である、請求項9に記載の方法。
- 前記有機溶媒がエタノールまたはジイソプロピルエーテル(DIPE)である、請求項9に記載の方法。
- 前記塩基が水酸化ナトリウム、水酸化カリウムまたは第四級ジメチルアミンの塩または第四級ジエチルアミンの塩である、請求項9に記載の方法。
- 前記塩基が、水酸化ナトリウム、水酸化カリウムまたは第四級ジメチルアミンの塩または第四級ジメチルアミンの塩である、請求項11に記載の方法。
- 前記溶媒が、極性有機溶媒と混合された水である、請求項9に記載の方法。
- 極性有機溶媒に対する水の比率が5:1から10:0.1の範囲である、請求項14に記載の方法。
- 溶媒が極性有機溶媒と混合された水である、請求項11に記載の方法。
- 極性有機溶媒に対する水の比率が5:1から10:0.1の範囲である、請求項16に記載の方法。
- 前記溶媒が、極性有機溶媒と混合された水である、請求項12に記載の方法。
- 極性有機溶媒に対する水の比率が5:1から10:0.1の範囲である、請求項18に記載の方法。
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Non-Patent Citations (2)
Title |
---|
C.G.WERMUTH編, 「最新 創薬化学 下巻」, vol. pp.347-365, JPN6014029314, 1999, ISSN: 0004959824 * |
高田則幸: "創薬段階における原薬Formスクリーニングと選択", PHARM STAGE, vol. 6, no. 10, JPN6009053755, 15 January 2007 (2007-01-15), pages 20 - 25, ISSN: 0004959825 * |
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