CN106660949B - N-[4-(1-氨基乙基)-苯基]-磺酰胺衍生物的手性拆分方法 - Google Patents
N-[4-(1-氨基乙基)-苯基]-磺酰胺衍生物的手性拆分方法 Download PDFInfo
- Publication number
- CN106660949B CN106660949B CN201680002149.0A CN201680002149A CN106660949B CN 106660949 B CN106660949 B CN 106660949B CN 201680002149 A CN201680002149 A CN 201680002149A CN 106660949 B CN106660949 B CN 106660949B
- Authority
- CN
- China
- Prior art keywords
- compound
- stereoisomers
- mixture
- acid
- molar equivalent
- Prior art date
- 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.)
- Active
Links
- 238000000034 method Methods 0.000 title claims abstract description 91
- -1 N- [4- (1-aminoethyl) -phenyl ] -sulfamide derivative Chemical class 0.000 title claims description 13
- 150000001875 compounds Chemical class 0.000 claims abstract description 130
- 239000000203 mixture Substances 0.000 claims abstract description 111
- 230000008569 process Effects 0.000 claims abstract description 35
- MIOPJNTWMNEORI-GMSGAONNSA-N (S)-camphorsulfonic acid Chemical compound C1C[C@@]2(CS(O)(=O)=O)C(=O)C[C@@H]1C2(C)C MIOPJNTWMNEORI-GMSGAONNSA-N 0.000 claims abstract description 32
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 claims abstract description 30
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 claims abstract description 30
- 229960002510 mandelic acid Drugs 0.000 claims abstract description 30
- 238000002156 mixing Methods 0.000 claims abstract description 18
- 229910052799 carbon Inorganic materials 0.000 claims abstract description 15
- 150000003839 salts Chemical class 0.000 claims description 44
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 39
- 239000002904 solvent Substances 0.000 claims description 29
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 28
- 101100348848 Mus musculus Notch4 gene Proteins 0.000 claims description 19
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 18
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 17
- 229910052739 hydrogen Inorganic materials 0.000 claims description 10
- 239000001257 hydrogen Substances 0.000 claims description 10
- FORFBJNKDYMFQR-RXMQYKEDSA-N n-[4-[(1r)-1-aminoethyl]-2,6-difluorophenyl]methanesulfonamide Chemical compound C[C@@H](N)C1=CC(F)=C(NS(C)(=O)=O)C(F)=C1 FORFBJNKDYMFQR-RXMQYKEDSA-N 0.000 claims description 9
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 238000002360 preparation method Methods 0.000 claims description 8
- UKGJZDSUJSPAJL-GFCCVEGCSA-N n-[(1r)-1-[3,5-difluoro-4-(methanesulfonamido)phenyl]ethyl]-3-[2-propyl-6-(trifluoromethyl)pyridin-3-yl]prop-2-enamide Chemical compound CCCC1=NC(C(F)(F)F)=CC=C1C=CC(=O)N[C@H](C)C1=CC(F)=C(NS(C)(=O)=O)C(F)=C1 UKGJZDSUJSPAJL-GFCCVEGCSA-N 0.000 claims description 7
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 6
- 125000000304 alkynyl group Chemical group 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 150000003254 radicals Chemical class 0.000 claims description 6
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 229910052731 fluorine Inorganic materials 0.000 claims description 5
- YONLFQNRGZXBBF-ZIAGYGMSSA-N (2r,3r)-2,3-dibenzoyloxybutanedioic acid Chemical compound O([C@@H](C(=O)O)[C@@H](OC(=O)C=1C=CC=CC=1)C(O)=O)C(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-ZIAGYGMSSA-N 0.000 claims description 4
- IWYDHOAUDWTVEP-SSDOTTSWSA-N (R)-mandelic acid Chemical compound OC(=O)[C@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-SSDOTTSWSA-N 0.000 claims description 4
- IWYDHOAUDWTVEP-ZETCQYMHSA-N (S)-mandelic acid Chemical compound OC(=O)[C@@H](O)C1=CC=CC=C1 IWYDHOAUDWTVEP-ZETCQYMHSA-N 0.000 claims description 4
- CNCIJHJOEHBPBF-UHFFFAOYSA-N 3-[2-propyl-6-(trifluoromethyl)pyridin-3-yl]prop-2-enoic acid Chemical compound CCCC1=NC(C(F)(F)F)=CC=C1C=CC(O)=O CNCIJHJOEHBPBF-UHFFFAOYSA-N 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 4
- CMIBUZBMZCBCAT-HZPDHXFCSA-N (2r,3r)-2,3-bis[(4-methylbenzoyl)oxy]butanedioic acid Chemical compound C1=CC(C)=CC=C1C(=O)O[C@@H](C(O)=O)[C@H](C(O)=O)OC(=O)C1=CC=C(C)C=C1 CMIBUZBMZCBCAT-HZPDHXFCSA-N 0.000 claims description 3
- CMIBUZBMZCBCAT-HOTGVXAUSA-N (2s,3s)-2,3-bis[(4-methylbenzoyl)oxy]butanedioic acid Chemical compound C1=CC(C)=CC=C1C(=O)O[C@H](C(O)=O)[C@@H](C(O)=O)OC(=O)C1=CC=C(C)C=C1 CMIBUZBMZCBCAT-HOTGVXAUSA-N 0.000 claims description 3
- MIOPJNTWMNEORI-XVKPBYJWSA-N (R)-camphorsulfonic acid Chemical compound C1C[C@]2(CS(O)(=O)=O)C(=O)C[C@H]1C2(C)C MIOPJNTWMNEORI-XVKPBYJWSA-N 0.000 claims description 3
- YONLFQNRGZXBBF-UHFFFAOYSA-N 2,3-dibenzoyloxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)OC(C(O)=O)C(C(=O)O)OC(=O)C1=CC=CC=C1 YONLFQNRGZXBBF-UHFFFAOYSA-N 0.000 claims description 3
- 238000009835 boiling Methods 0.000 claims description 3
- 229910052794 bromium Inorganic materials 0.000 claims description 3
- 238000004090 dissolution Methods 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 229910052740 iodine Inorganic materials 0.000 claims description 3
- 238000004519 manufacturing process Methods 0.000 claims description 3
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 3
- 239000000376 reactant Substances 0.000 claims description 3
- 239000011541 reaction mixture Substances 0.000 claims description 3
- 239000011877 solvent mixture Substances 0.000 claims description 3
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 2
- 150000001298 alcohols Chemical class 0.000 claims description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 230000008878 coupling Effects 0.000 claims description 2
- 238000010168 coupling process Methods 0.000 claims description 2
- 238000005859 coupling reaction Methods 0.000 claims description 2
- 235000019253 formic acid Nutrition 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 claims description 2
- 125000001147 pentyl group Chemical group C(CCCC)* 0.000 claims description 2
- 235000019260 propionic acid Nutrition 0.000 claims description 2
- 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 claims description 2
- 230000003287 optical effect Effects 0.000 abstract description 83
- 239000002253 acid Substances 0.000 abstract description 29
- 125000004432 carbon atom Chemical group C* 0.000 abstract description 12
- 239000003814 drug Substances 0.000 abstract description 11
- 125000003277 amino group Chemical group 0.000 abstract description 7
- 239000002537 cosmetic Substances 0.000 abstract description 2
- FORFBJNKDYMFQR-UHFFFAOYSA-N n-[4-(1-aminoethyl)-2,6-difluorophenyl]methanesulfonamide Chemical compound CC(N)C1=CC(F)=C(NS(C)(=O)=O)C(F)=C1 FORFBJNKDYMFQR-UHFFFAOYSA-N 0.000 description 15
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 11
- 238000006243 chemical reaction Methods 0.000 description 11
- 239000003586 protic polar solvent Substances 0.000 description 11
- 229960001367 tartaric acid Drugs 0.000 description 11
- 235000002906 tartaric acid Nutrition 0.000 description 11
- 239000011975 tartaric acid Substances 0.000 description 11
- 230000000694 effects Effects 0.000 description 10
- 238000003756 stirring Methods 0.000 description 10
- VHUUQVKOLVNVRT-UHFFFAOYSA-N Ammonium hydroxide Chemical compound [NH4+].[OH-] VHUUQVKOLVNVRT-UHFFFAOYSA-N 0.000 description 9
- ITRWGGRQRXTXBG-UHFFFAOYSA-N CC(N)C1=CC=C(NS(=O)=O)C=C1 Chemical class CC(N)C1=CC=C(NS(=O)=O)C=C1 ITRWGGRQRXTXBG-UHFFFAOYSA-N 0.000 description 8
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
- 235000011114 ammonium hydroxide Nutrition 0.000 description 8
- 229940079593 drug Drugs 0.000 description 8
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonium chloride Substances [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 7
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 7
- 238000011914 asymmetric synthesis Methods 0.000 description 7
- 239000000243 solution Substances 0.000 description 7
- 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 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- 238000012360 testing method Methods 0.000 description 6
- 239000005557 antagonist Substances 0.000 description 5
- 239000012752 auxiliary agent Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- KIUMMUBSPKGMOY-UHFFFAOYSA-N 3,3'-Dithiobis(6-nitrobenzoic acid) Chemical compound C1=C([N+]([O-])=O)C(C(=O)O)=CC(SSC=2C=C(C(=CC=2)[N+]([O-])=O)C(O)=O)=C1 KIUMMUBSPKGMOY-UHFFFAOYSA-N 0.000 description 4
- 102000003566 TRPV1 Human genes 0.000 description 4
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 4
- 201000010099 disease Diseases 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
- 238000001914 filtration Methods 0.000 description 4
- 238000004128 high performance liquid chromatography Methods 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- XGTMJUVUJJEZAD-NUBCRITNSA-N n-[4-[(1r)-1-aminoethyl]-2,6-difluorophenyl]methanesulfonamide;hydrochloride Chemical compound Cl.C[C@@H](N)C1=CC(F)=C(NS(C)(=O)=O)C(F)=C1 XGTMJUVUJJEZAD-NUBCRITNSA-N 0.000 description 4
- 150000003892 tartrate salts Chemical class 0.000 description 4
- UKGJZDSUJSPAJL-YPUOHESYSA-N (e)-n-[(1r)-1-[3,5-difluoro-4-(methanesulfonamido)phenyl]ethyl]-3-[2-propyl-6-(trifluoromethyl)pyridin-3-yl]prop-2-enamide Chemical compound CCCC1=NC(C(F)(F)F)=CC=C1\C=C\C(=O)N[C@H](C)C1=CC(F)=C(NS(C)(=O)=O)C(F)=C1 UKGJZDSUJSPAJL-YPUOHESYSA-N 0.000 description 3
- KMGUEILFFWDGFV-UHFFFAOYSA-N 2-benzoyl-2-benzoyloxy-3-hydroxybutanedioic acid Chemical compound C=1C=CC=CC=1C(=O)C(C(C(O)=O)O)(C(O)=O)OC(=O)C1=CC=CC=C1 KMGUEILFFWDGFV-UHFFFAOYSA-N 0.000 description 3
- OUBORTRIKPEZMG-UHFFFAOYSA-N INT-2 Chemical compound Nc1c(ncn1-c1ccc(F)cc1)C(=N)C#N OUBORTRIKPEZMG-UHFFFAOYSA-N 0.000 description 3
- 208000002193 Pain Diseases 0.000 description 3
- 102100029613 Transient receptor potential cation channel subfamily V member 1 Human genes 0.000 description 3
- 101001060278 Xenopus laevis Fibroblast growth factor 3 Proteins 0.000 description 3
- 230000000052 comparative effect Effects 0.000 description 3
- 238000002474 experimental method Methods 0.000 description 3
- 238000009472 formulation Methods 0.000 description 3
- 238000005259 measurement Methods 0.000 description 3
- FORFBJNKDYMFQR-YFKPBYRVSA-N n-[4-[(1s)-1-aminoethyl]-2,6-difluorophenyl]methanesulfonamide Chemical compound C[C@H](N)C1=CC(F)=C(NS(C)(=O)=O)C(F)=C1 FORFBJNKDYMFQR-YFKPBYRVSA-N 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- 238000000926 separation method Methods 0.000 description 3
- 239000000126 substance Substances 0.000 description 3
- NTOIKDYVJIWVSU-UHFFFAOYSA-N 2,3-dihydroxy-2,3-bis(4-methylbenzoyl)butanedioic acid Chemical compound C1=CC(C)=CC=C1C(=O)C(O)(C(O)=O)C(O)(C(O)=O)C(=O)C1=CC=C(C)C=C1 NTOIKDYVJIWVSU-UHFFFAOYSA-N 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 2
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
- 206010020751 Hypersensitivity Diseases 0.000 description 2
- 208000022559 Inflammatory bowel disease Diseases 0.000 description 2
- 108010062740 TRPV Cation Channels Proteins 0.000 description 2
- 108050004388 Transient receptor potential cation channel subfamily V member 1 Proteins 0.000 description 2
- 208000026935 allergic disease Diseases 0.000 description 2
- 238000004296 chiral HPLC Methods 0.000 description 2
- 238000001514 detection method Methods 0.000 description 2
- 239000002360 explosive Substances 0.000 description 2
- 239000012467 final product Substances 0.000 description 2
- 208000021302 gastroesophageal reflux disease Diseases 0.000 description 2
- 230000009610 hypersensitivity Effects 0.000 description 2
- 208000002551 irritable bowel syndrome Diseases 0.000 description 2
- 239000011259 mixed solution Substances 0.000 description 2
- DCEDNQCQVNFNSU-UHFFFAOYSA-N n-[4-(1-aminoethyl)phenyl]methanesulfonamide Chemical compound CC(N)C1=CC=C(NS(C)(=O)=O)C=C1 DCEDNQCQVNFNSU-UHFFFAOYSA-N 0.000 description 2
- 201000001119 neuropathy Diseases 0.000 description 2
- 230000007823 neuropathy Effects 0.000 description 2
- 239000008194 pharmaceutical composition Substances 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 239000002798 polar solvent Substances 0.000 description 2
- 239000002244 precipitate Substances 0.000 description 2
- 230000001376 precipitating effect Effects 0.000 description 2
- 230000002265 prevention Effects 0.000 description 2
- 229910000033 sodium borohydride Inorganic materials 0.000 description 2
- 239000012279 sodium borohydride Substances 0.000 description 2
- BAZAXWOYCMUHIX-UHFFFAOYSA-M sodium perchlorate Chemical compound [Na+].[O-]Cl(=O)(=O)=O BAZAXWOYCMUHIX-UHFFFAOYSA-M 0.000 description 2
- 229910001488 sodium perchlorate Inorganic materials 0.000 description 2
- 239000012453 solvate Substances 0.000 description 2
- 238000003786 synthesis reaction Methods 0.000 description 2
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 2
- 239000003643 water by type Substances 0.000 description 2
- ZMYFCFLJBGAQRS-IRXDYDNUSA-N (2R,3S)-epoxiconazole Chemical compound C1=CC(F)=CC=C1[C@@]1(CN2N=CN=C2)[C@H](C=2C(=CC=CC=2)Cl)O1 ZMYFCFLJBGAQRS-IRXDYDNUSA-N 0.000 description 1
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 1
- LLAPDLPYIYKTGQ-UHFFFAOYSA-N 1-aminoethyl Chemical group C[CH]N LLAPDLPYIYKTGQ-UHFFFAOYSA-N 0.000 description 1
- 238000005160 1H NMR spectroscopy Methods 0.000 description 1
- 201000004384 Alopecia Diseases 0.000 description 1
- 206010002556 Ankylosing Spondylitis Diseases 0.000 description 1
- 208000008035 Back Pain Diseases 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 206010011224 Cough Diseases 0.000 description 1
- 208000011231 Crohn disease Diseases 0.000 description 1
- 239000005767 Epoxiconazole Substances 0.000 description 1
- 208000001640 Fibromyalgia Diseases 0.000 description 1
- 206010019233 Headaches Diseases 0.000 description 1
- 206010020112 Hirsutism Diseases 0.000 description 1
- 208000019695 Migraine disease Diseases 0.000 description 1
- 206010028116 Mucosal inflammation Diseases 0.000 description 1
- 208000030858 Myofascial Pain Syndromes Diseases 0.000 description 1
- 208000028389 Nerve injury Diseases 0.000 description 1
- 206010033645 Pancreatitis Diseases 0.000 description 1
- 208000004550 Postoperative Pain Diseases 0.000 description 1
- 206010037083 Prurigo Diseases 0.000 description 1
- 208000003251 Pruritus Diseases 0.000 description 1
- 201000004681 Psoriasis Diseases 0.000 description 1
- 206010040880 Skin irritation Diseases 0.000 description 1
- 208000007107 Stomach Ulcer Diseases 0.000 description 1
- 208000006011 Stroke Diseases 0.000 description 1
- 102000011040 TRPV Cation Channels Human genes 0.000 description 1
- 208000009205 Tinnitus Diseases 0.000 description 1
- 239000005846 Triadimenol Substances 0.000 description 1
- 206010046543 Urinary incontinence Diseases 0.000 description 1
- 208000012886 Vertigo Diseases 0.000 description 1
- 230000001594 aberrant effect Effects 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 230000000172 allergic effect Effects 0.000 description 1
- 231100000360 alopecia Toxicity 0.000 description 1
- 230000002917 arthritic effect Effects 0.000 description 1
- 208000006673 asthma Diseases 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- 208000010668 atopic eczema Diseases 0.000 description 1
- 230000015572 biosynthetic process Effects 0.000 description 1
- 239000003153 chemical reaction reagent Substances 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 201000003146 cystitis Diseases 0.000 description 1
- 206010012601 diabetes mellitus Diseases 0.000 description 1
- 239000003937 drug carrier Substances 0.000 description 1
- 230000000857 drug effect Effects 0.000 description 1
- 208000000718 duodenal ulcer Diseases 0.000 description 1
- 230000007613 environmental effect Effects 0.000 description 1
- 238000003912 environmental pollution Methods 0.000 description 1
- 230000001667 episodic effect Effects 0.000 description 1
- 230000002550 fecal effect Effects 0.000 description 1
- 125000000524 functional group Chemical group 0.000 description 1
- 230000000855 fungicidal effect Effects 0.000 description 1
- 230000002496 gastric effect Effects 0.000 description 1
- 231100001261 hazardous Toxicity 0.000 description 1
- 231100000869 headache Toxicity 0.000 description 1
- 230000001939 inductive effect Effects 0.000 description 1
- 230000002757 inflammatory effect Effects 0.000 description 1
- 239000010805 inorganic waste Substances 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- 206010027599 migraine Diseases 0.000 description 1
- 238000012986 modification Methods 0.000 description 1
- 230000004048 modification Effects 0.000 description 1
- 208000031225 myocardial ischemia Diseases 0.000 description 1
- UKGJZDSUJSPAJL-UHFFFAOYSA-N n-[1-[3,5-difluoro-4-(methanesulfonamido)phenyl]ethyl]-3-[2-propyl-6-(trifluoromethyl)pyridin-3-yl]prop-2-enamide Chemical compound CCCC1=NC(C(F)(F)F)=CC=C1C=CC(=O)NC(C)C1=CC(F)=C(NS(C)(=O)=O)C(F)=C1 UKGJZDSUJSPAJL-UHFFFAOYSA-N 0.000 description 1
- IZSYQAHASDFPQK-UHFFFAOYSA-N n-[4-[1-(tert-butylsulfinylamino)ethyl]-2,6-difluorophenyl]methanesulfonamide Chemical compound CC(C)(C)S(=O)NC(C)C1=CC(F)=C(NS(C)(=O)=O)C(F)=C1 IZSYQAHASDFPQK-UHFFFAOYSA-N 0.000 description 1
- 230000008764 nerve damage Effects 0.000 description 1
- 208000004296 neuralgia Diseases 0.000 description 1
- 230000004770 neurodegeneration Effects 0.000 description 1
- 230000002981 neuropathic effect Effects 0.000 description 1
- 208000021722 neuropathic pain Diseases 0.000 description 1
- 239000010815 organic waste Substances 0.000 description 1
- 201000008482 osteoarthritis Diseases 0.000 description 1
- 230000001575 pathological effect Effects 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 230000009467 reduction Effects 0.000 description 1
- 206010039073 rheumatoid arthritis Diseases 0.000 description 1
- 206010039083 rhinitis Diseases 0.000 description 1
- 208000017520 skin disease Diseases 0.000 description 1
- 230000036556 skin irritation Effects 0.000 description 1
- 231100000475 skin irritation Toxicity 0.000 description 1
- 230000000638 stimulation Effects 0.000 description 1
- 229940124530 sulfonamide Drugs 0.000 description 1
- 238000001308 synthesis method Methods 0.000 description 1
- 230000002194 synthesizing effect Effects 0.000 description 1
- 231100000886 tinnitus Toxicity 0.000 description 1
- 231100000419 toxicity Toxicity 0.000 description 1
- 230000001988 toxicity Effects 0.000 description 1
- 230000009466 transformation Effects 0.000 description 1
- BAZVSMNPJJMILC-UHFFFAOYSA-N triadimenol Chemical compound C1=NC=NN1C(C(O)C(C)(C)C)OC1=CC=C(Cl)C=C1 BAZVSMNPJJMILC-UHFFFAOYSA-N 0.000 description 1
- 231100000889 vertigo Toxicity 0.000 description 1
- 230000001720 vestibular Effects 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/36—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of amides of sulfonic acids
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/42—Separation; Purification; Stabilisation; Use of additives
- C07C303/44—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/08—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atom of at least one of the sulfonamide groups bound to a carbon atom of a six-membered aromatic ring
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B57/00—Separation of optically-active compounds
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C303/00—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides
- C07C303/42—Separation; Purification; Stabilisation; Use of additives
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C63/00—Compounds having carboxyl groups bound to a carbon atoms of six-membered aromatic rings
- C07C63/04—Monocyclic monocarboxylic acids
- C07C63/06—Benzoic acid
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D213/00—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members
- C07D213/02—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members
- C07D213/04—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom
- C07D213/24—Heterocyclic compounds containing six-membered rings, not condensed with other rings, with one nitrogen atom as the only ring hetero atom and three or more double bonds between ring members or between ring members and non-ring members having three double bonds between ring members or between ring members and non-ring members having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen or carbon atoms directly attached to the ring nitrogen atom with substituted hydrocarbon radicals attached to ring carbon atoms
- C07D213/54—Radicals substituted by carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals
- C07D213/56—Amides
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07B—GENERAL METHODS OF ORGANIC CHEMISTRY; APPARATUS THEREFOR
- C07B2200/00—Indexing scheme relating to specific properties of organic compounds
- C07B2200/07—Optical isomers
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Pyridine Compounds (AREA)
- Cosmetics (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| KR1020150024334A KR20160101554A (ko) | 2015-02-17 | 2015-02-17 | N-[4-(1-아미노에틸)-페닐]-메탄술폰아미드 유도체의 카이랄 분할 방법 |
| KR10-2015-0024334 | 2015-02-17 | ||
| EP15174617 | 2015-06-30 | ||
| EP15174617.9 | 2015-06-30 | ||
| PCT/KR2016/001474 WO2016133317A1 (ko) | 2015-02-17 | 2016-02-15 | Ｎ-[4-(1-아미노에틸)-페닐]-술폰아미드 유도체의 카이랄 분할 방법 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| CN106660949A CN106660949A (zh) | 2017-05-10 |
| CN106660949B true CN106660949B (zh) | 2020-11-13 |
Family
ID=56692658
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CN201680002149.0A Active CN106660949B (zh) | 2015-02-17 | 2016-02-15 | N-[4-(1-氨基乙基)-苯基]-磺酰胺衍生物的手性拆分方法 |
Country Status (8)
| Country | Link |
|---|---|
| US (1) | US10479763B2 (enExample) |
| EP (1) | EP3162793B1 (enExample) |
| JP (1) | JP6687596B2 (enExample) |
| KR (1) | KR101791119B1 (enExample) |
| CN (1) | CN106660949B (enExample) |
| BR (1) | BR112017001516B1 (enExample) |
| TW (1) | TWI687396B (enExample) |
| WO (1) | WO2016133317A1 (enExample) |
Families Citing this family (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| KR102565407B1 (ko) * | 2016-01-04 | 2023-08-10 | (주)아모레퍼시픽 | 극성 비양자성 용매를 이용한 n-[4-(1-아미노에틸)-페닐]-술폰아미드 유도체의 카이랄 분할 방법 |
| KR102599958B1 (ko) | 2016-09-28 | 2023-11-09 | (주)아모레퍼시픽 | (r)-n-[4-(1-아미노-에틸)-2,6-다이플루오로-페닐]-메테인설폰아마이드의 제조방법 |
| KR102587339B1 (ko) * | 2016-12-22 | 2023-10-12 | (주)아모레퍼시픽 | N-[4-(1-아미노-에틸)-2,6-다이플루오로-페닐]-메테인설폰아마이드의 거울상 이성질체들의 라세미화 방법 |
| CN109608368B (zh) * | 2018-10-24 | 2021-03-09 | 常州市阳光药业有限公司 | N-[4-(1-氨基乙基)-2,6-二氟苯基]甲磺酰胺的合成及拆分方法 |
| KR20200053746A (ko) * | 2018-11-09 | 2020-05-19 | (주)아모레퍼시픽 | 졸-겔 조성물 |
| CN115103836A (zh) * | 2020-02-16 | 2022-09-23 | 艾雅拉制药公司 | 制备手性苯并二氮杂卓酮衍生物的方法 |
Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| EP1862454A1 (en) * | 2006-06-02 | 2007-12-05 | Amorepacific Corporation | Novel compounds, isomer thereof or pharmaceutically acceptable salts thereof as vanilloid receptor antagonist; and a pharmaceutical composition containing the same |
| CN101160285A (zh) * | 2005-03-17 | 2008-04-09 | 辉瑞大药厂 | 适用于治疗疼痛的n-(n-磺酰氨基甲基)环丙烷甲酰胺衍生物 |
Family Cites Families (14)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPS60152425A (ja) * | 1984-01-20 | 1985-08-10 | Oyo Seikagaku Kenkyusho:Kk | ラセミ体の新規な光学分割法 |
| US4968837A (en) | 1989-07-28 | 1990-11-06 | Ethyl Corporation | Resolution of racemic mixtures |
| ATE125254T1 (de) * | 1989-09-19 | 1995-08-15 | Hoechst Roussel Pharma | Verfahren zur racematspaltung von 5-alkoxy- substituierten (+/-)-1,3- dimethyloxindolylethylaminen. |
| US6265615B1 (en) | 1998-07-01 | 2001-07-24 | The Regents Of The University Of California | Chiral recognition polymer and its use to separate enantiomers |
| DE19956786A1 (de) * | 1999-11-25 | 2001-05-31 | Basf Ag | Verfahren zur Herstellung optisch aktiver Amine |
| US7301023B2 (en) * | 2001-05-31 | 2007-11-27 | Pfizer Inc. | Chiral salt resolution |
| US20120041225A1 (en) * | 2006-02-03 | 2012-02-16 | Vaidya Niteen A | Kit for automated resolving agent selection and method thereof |
| WO2007129188A1 (en) * | 2006-05-10 | 2007-11-15 | Pfizer Japan Inc. | Cyclopropanecarboxamide compound |
| WO2007133637A2 (en) | 2006-05-10 | 2007-11-22 | Renovis, Inc. | Amide derivatives as ion-channel ligands and pharmaceutical compositions and methods of using the same |
| PL2054411T3 (pl) | 2006-07-27 | 2015-02-27 | Amorepacific Corp | Nowe związki, ich izomery lub ich farmaceutycznie dopuszczalne sole jako antagoniści receptora waniloidowego oraz zawierające je kompozycje farmaceutyczne |
| EP1882687A1 (en) * | 2006-07-27 | 2008-01-30 | Amorepacific Corporation | Heterocyclic compounds useful as vanilloid receptor antagonists and pharmaceutical compositions containing the same |
| JP2011201778A (ja) * | 2008-07-23 | 2011-10-13 | Mochida Pharmaceut Co Ltd | ｐ−置換アリールアセトアミドを有するヘテロシクリデン誘導体 |
| EP2356121A1 (en) | 2008-11-07 | 2011-08-17 | Cipla Limited | Process for resolving zopiclone |
| KR20160101554A (ko) | 2015-02-17 | 2016-08-25 | (주)아모레퍼시픽 | N-[4-(1-아미노에틸)-페닐]-메탄술폰아미드 유도체의 카이랄 분할 방법 |
-
2016
- 2016-02-15 CN CN201680002149.0A patent/CN106660949B/zh active Active
- 2016-02-15 WO PCT/KR2016/001474 patent/WO2016133317A1/ko not_active Ceased
- 2016-02-15 JP JP2017502582A patent/JP6687596B2/ja active Active
- 2016-02-15 EP EP16752647.4A patent/EP3162793B1/en active Active
- 2016-02-15 US US15/325,349 patent/US10479763B2/en active Active
- 2016-02-15 KR KR1020177000413A patent/KR101791119B1/ko not_active Expired - Fee Related
- 2016-02-15 BR BR112017001516-1A patent/BR112017001516B1/pt not_active IP Right Cessation
- 2016-02-16 TW TW105104399A patent/TWI687396B/zh active
Patent Citations (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN101160285A (zh) * | 2005-03-17 | 2008-04-09 | 辉瑞大药厂 | 适用于治疗疼痛的n-(n-磺酰氨基甲基)环丙烷甲酰胺衍生物 |
| EP1862454A1 (en) * | 2006-06-02 | 2007-12-05 | Amorepacific Corporation | Novel compounds, isomer thereof or pharmaceutically acceptable salts thereof as vanilloid receptor antagonist; and a pharmaceutical composition containing the same |
Non-Patent Citations (2)
| Title |
|---|
| Chain-branched 1,3-dibenzylthioureas as vanilloid receptor 1 antagonists;Chong Hyun Ryu等;《Bioorganic & Medicinal Chemistry Letters》;20041231;第14卷;1751-1755 * |
| Oral and topical pharmacokinetic studies of a novel TRPV1 antagonist,PAC-14028 in rats and minipigs using liquid chromatography/tandem mass spectrometric method;Yang-Hui Park等;《Journal of Pharmaceutical and Biomedical Analysis》;20121117;第61卷;8-14 * |
Also Published As
| Publication number | Publication date |
|---|---|
| TWI687396B (zh) | 2020-03-11 |
| BR112017001516A2 (pt) | 2018-01-30 |
| US10479763B2 (en) | 2019-11-19 |
| JP6687596B2 (ja) | 2020-04-22 |
| US20170342027A1 (en) | 2017-11-30 |
| TW201636319A (zh) | 2016-10-16 |
| WO2016133317A1 (ko) | 2016-08-25 |
| KR20170042548A (ko) | 2017-04-19 |
| EP3162793B1 (en) | 2019-04-10 |
| BR112017001516B1 (pt) | 2023-10-31 |
| CN106660949A (zh) | 2017-05-10 |
| KR101791119B1 (ko) | 2017-11-20 |
| EP3162793A1 (en) | 2017-05-03 |
| EP3162793A4 (en) | 2018-01-03 |
| JP2018506503A (ja) | 2018-03-08 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| CN106660949B (zh) | N-[4-(1-氨基乙基)-苯基]-磺酰胺衍生物的手性拆分方法 | |
| TWI725098B (zh) | 藉由使用極性非質子性溶劑掌性解析n-[4-(1-胺基乙基)-苯基]-磺醯胺衍生物之方法 | |
| KR20160101554A (ko) | N-[4-(1-아미노에틸)-페닐]-메탄술폰아미드 유도체의 카이랄 분할 방법 | |
| WO2014157612A1 (ja) | （１ｓ，４ｓ，５ｓ）－４－ブロモ－６－オキサビシクロ［３．２．１］オクタン－７－オンの製造方法 | |
| FR2883285A1 (fr) | Sel besylate de la 7-(2-(4-(3-trifluoromethyl-phenyl) -1,2,3,6-tetrahudro-pyrid-1-yl)ethyl) isoquinoleine, sa preparation et son utilisation en therapeutique | |
| HK1237332A1 (en) | Chiral resolution method of n-[4-(1-aminoethyl)-phenyl]-sulfonamide derivatives | |
| EP2345655A1 (en) | A process for racemisation of 6-(5-chloropyridin-2-yl)-7-(4-methyl-1-piperazinyl)carbonyloxy-7-oxo-6,7-dihydro-5H-pyrrolo[3,4-b]pyrazine | |
| HK1237332B (zh) | N‑[4‑(1‑氨基乙基)‑苯基]‑磺酰胺衍生物的手性拆分方法 | |
| TWI741111B (zh) | N-[4-(1-氨乙基)-2,6-二氟苯基]-甲磺醯胺之鏡像異構物的消旋方法 | |
| US10858315B2 (en) | Method for preparing (R)-N-[4-(1-amino-ethyl)-2,6-difluoro-phenyl]-methanesulfonamide | |
| CN110922354B (zh) | 一种1-r-3-氟哌啶-4-羧酸的化学拆分制备方法及其产物 | |
| EP2348013A1 (en) | Process for preparation of intermediates of arformoterol | |
| WO2010068049A2 (en) | Process for preparing (r)-(+)-lansoprazole and intermediate used therein | |
| HK40005103A (en) | Method for preparing (r)-n-[4-(1-amino-ethyl)-2,6-difluoro-phenyl]-methanesulfonamide | |
| JP2024501494A (ja) | オシメルチニブまたはその塩を調製するための改良された方法 | |
| CN117088829A (zh) | 1-异丙基-4-(对甲氧基苯基)哌嗪或其氢卤酸盐的合成方法 | |
| AU2018264079A1 (en) | New benzimidazole derivatives as dual histamine H1 and histamine H4 receptor ligands | |
| EP2396334A1 (fr) | Derives de n-[(2-aza-bicyclo[2.1.1]hex-1-yl]-aryl-methyl]-benzamide, leur preparation et leur application en therapeutique | |
| WO2011054185A1 (zh) | 芳烷哌嗪衍生物光学异构体、其制备方法及应用 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PB01 | Publication | ||
| PB01 | Publication | ||
| SE01 | Entry into force of request for substantive examination | ||
| SE01 | Entry into force of request for substantive examination | ||
| REG | Reference to a national code |
Ref country code: HK Ref legal event code: DE Ref document number: 1237332 Country of ref document: HK |
|
| GR01 | Patent grant | ||
| GR01 | Patent grant |