JP2014533292A - Ｎ−置換された２−（アセチルアミノ）−ｎ’−ベンジル−３−メトキシプロパンアミドの製造方法 - Google Patents
Ｎ−置換された２−（アセチルアミノ）−ｎ’−ベンジル−３−メトキシプロパンアミドの製造方法 Download PDFInfo
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- JP2014533292A JP2014533292A JP2014541630A JP2014541630A JP2014533292A JP 2014533292 A JP2014533292 A JP 2014533292A JP 2014541630 A JP2014541630 A JP 2014541630A JP 2014541630 A JP2014541630 A JP 2014541630A JP 2014533292 A JP2014533292 A JP 2014533292A
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- 238000000034 method Methods 0.000 title claims abstract description 107
- 230000008569 process Effects 0.000 title claims abstract description 15
- 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 title abstract description 3
- 229960002623 lacosamide Drugs 0.000 claims abstract description 37
- 239000002253 acid Substances 0.000 claims abstract description 21
- 150000001875 compounds Chemical class 0.000 claims description 123
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 120
- 239000000203 mixture Substances 0.000 claims description 60
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 47
- YSEFYOVWKJXNCH-UHFFFAOYSA-N 2-methoxyacetaldehyde Chemical compound COCC=O YSEFYOVWKJXNCH-UHFFFAOYSA-N 0.000 claims description 38
- RIWNFZUWWRVGEU-UHFFFAOYSA-N isocyanomethylbenzene Chemical compound [C-]#[N+]CC1=CC=CC=C1 RIWNFZUWWRVGEU-UHFFFAOYSA-N 0.000 claims description 37
- 239000002904 solvent Substances 0.000 claims description 33
- -1 tert-butyl- Chemical group 0.000 claims description 33
- 238000006243 chemical reaction Methods 0.000 claims description 24
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 24
- 125000003118 aryl group Chemical group 0.000 claims description 21
- 150000001412 amines Chemical class 0.000 claims description 18
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 16
- 150000003839 salts Chemical class 0.000 claims description 14
- 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 12
- 235000019253 formic acid Nutrition 0.000 claims description 12
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 10
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 9
- 150000007513 acids Chemical class 0.000 claims description 9
- 238000004587 chromatography analysis Methods 0.000 claims description 9
- 239000001257 hydrogen Substances 0.000 claims description 9
- 229910052739 hydrogen Inorganic materials 0.000 claims description 9
- 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 claims description 9
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 8
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 8
- 238000002425 crystallisation Methods 0.000 claims description 8
- 230000008025 crystallization Effects 0.000 claims description 8
- 229910052736 halogen Inorganic materials 0.000 claims description 8
- 150000002367 halogens Chemical class 0.000 claims description 8
- 238000004519 manufacturing process Methods 0.000 claims description 8
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 7
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
- 125000002619 bicyclic group Chemical group 0.000 claims description 7
- 125000004432 carbon atom Chemical group C* 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 7
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 7
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 7
- 229910052723 transition metal Inorganic materials 0.000 claims description 7
- 150000003624 transition metals Chemical class 0.000 claims description 7
- 239000003153 chemical reaction reagent Substances 0.000 claims description 6
- 125000002927 2-methoxybenzyl group Chemical group [H]C1=C([H])C([H])=C(C(OC([H])([H])[H])=C1[H])C([H])([H])* 0.000 claims description 5
- 125000002774 3,4-dimethoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C(OC([H])([H])[H])=C1OC([H])([H])[H])C([H])([H])* 0.000 claims description 5
- 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 claims description 5
- RRXSYZFVDIRTFB-UHFFFAOYSA-N C[CH]C1=CC=C(OC)C=C1 Chemical group C[CH]C1=CC=C(OC)C=C1 RRXSYZFVDIRTFB-UHFFFAOYSA-N 0.000 claims description 5
- 239000002841 Lewis acid Substances 0.000 claims description 5
- 150000007517 lewis acids Chemical class 0.000 claims description 5
- 229910052763 palladium Inorganic materials 0.000 claims description 5
- 239000011541 reaction mixture Substances 0.000 claims description 5
- 125000004343 1-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 claims description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 4
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 claims description 4
- MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 claims description 4
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 4
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
- 125000004129 indan-1-yl group Chemical group [H]C1=C([H])C([H])=C2C(=C1[H])C([H])([H])C([H])([H])C2([H])* 0.000 claims description 4
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 claims description 4
- 229910052703 rhodium Inorganic materials 0.000 claims description 4
- 239000010948 rhodium Substances 0.000 claims description 4
- MHOVAHRLVXNVSD-UHFFFAOYSA-N rhodium atom Chemical compound [Rh] MHOVAHRLVXNVSD-UHFFFAOYSA-N 0.000 claims description 4
- NQPDZGIKBAWPEJ-UHFFFAOYSA-N valeric acid Chemical compound CCCCC(O)=O NQPDZGIKBAWPEJ-UHFFFAOYSA-N 0.000 claims description 4
- JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 claims description 4
- 230000005526 G1 to G0 transition Effects 0.000 claims description 3
- 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 claims description 3
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 3
- 229910015900 BF3 Inorganic materials 0.000 claims description 2
- 229910021578 Iron(III) chloride Inorganic materials 0.000 claims description 2
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 2
- FOCAUTSVDIKZOP-UHFFFAOYSA-N chloroacetic acid Chemical compound OC(=O)CCl FOCAUTSVDIKZOP-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical group 0.000 claims description 2
- 229910052741 iridium Inorganic materials 0.000 claims description 2
- GKOZUEZYRPOHIO-UHFFFAOYSA-N iridium atom Chemical compound [Ir] GKOZUEZYRPOHIO-UHFFFAOYSA-N 0.000 claims description 2
- RBTARNINKXHZNM-UHFFFAOYSA-K iron trichloride Chemical compound Cl[Fe](Cl)Cl RBTARNINKXHZNM-UHFFFAOYSA-K 0.000 claims description 2
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 2
- RMIODHQZRUFFFF-UHFFFAOYSA-N methoxyacetic acid Chemical compound COCC(O)=O RMIODHQZRUFFFF-UHFFFAOYSA-N 0.000 claims description 2
- IUGYQRQAERSCNH-UHFFFAOYSA-N pivalic acid Chemical compound CC(C)(C)C(O)=O IUGYQRQAERSCNH-UHFFFAOYSA-N 0.000 claims description 2
- 229910052697 platinum Inorganic materials 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
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 claims description 2
- ITMCEJHCFYSIIV-UHFFFAOYSA-N triflic acid Chemical compound OS(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-N 0.000 claims description 2
- 229940005605 valeric acid Drugs 0.000 claims description 2
- 235000005074 zinc chloride Nutrition 0.000 claims description 2
- 239000011592 zinc chloride Substances 0.000 claims description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 1
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims 1
- 125000001037 p-tolyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)C([H])([H])[H] 0.000 claims 1
- YNJBWRMUSHSURL-UHFFFAOYSA-N trichloroacetic acid Chemical compound OC(=O)C(Cl)(Cl)Cl YNJBWRMUSHSURL-UHFFFAOYSA-N 0.000 claims 1
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 87
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 33
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 32
- 238000004128 high performance liquid chromatography Methods 0.000 description 30
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 28
- 229910052717 sulfur Inorganic materials 0.000 description 26
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 25
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
- 238000004296 chiral HPLC Methods 0.000 description 24
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 23
- 238000004237 preparative chromatography Methods 0.000 description 20
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 16
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 13
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 12
- 239000003921 oil Substances 0.000 description 12
- VPPJLAIAVCUEMN-GFCCVEGCSA-N lacosamide Chemical compound COC[C@@H](NC(C)=O)C(=O)NCC1=CC=CC=C1 VPPJLAIAVCUEMN-GFCCVEGCSA-N 0.000 description 11
- 239000000047 product Substances 0.000 description 9
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- 239000012230 colorless oil Substances 0.000 description 7
- 238000004440 column chromatography Methods 0.000 description 7
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
- 239000000377 silicon dioxide Substances 0.000 description 6
- 239000007787 solid Substances 0.000 description 6
- 238000003786 synthesis reaction Methods 0.000 description 6
- CGUNDOJCNKEPAU-IIBYNOLFSA-N (2r)-2-[acetyl-[(1r)-1-(4-methoxyphenyl)ethyl]amino]-n-benzyl-3-methoxypropanamide Chemical compound C1([C@@H](C)N([C@H](COC)C(=O)NCC=2C=CC=CC=2)C(C)=O)=CC=C(OC)C=C1 CGUNDOJCNKEPAU-IIBYNOLFSA-N 0.000 description 5
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 description 5
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 5
- 238000005112 continuous flow technique Methods 0.000 description 5
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 5
- 238000000926 separation method Methods 0.000 description 5
- CGUNDOJCNKEPAU-HRAATJIYSA-N (2r)-2-[acetyl-[(1s)-1-(4-methoxyphenyl)ethyl]amino]-n-benzyl-3-methoxypropanamide Chemical compound C1([C@H](C)N([C@H](COC)C(=O)NCC=2C=CC=CC=2)C(C)=O)=CC=C(OC)C=C1 CGUNDOJCNKEPAU-HRAATJIYSA-N 0.000 description 4
- GQHTUMJGOHRCHB-UHFFFAOYSA-N 2,3,4,6,7,8,9,10-octahydropyrimido[1,2-a]azepine Chemical compound C1CCCCN2CCCN=C21 GQHTUMJGOHRCHB-UHFFFAOYSA-N 0.000 description 4
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 4
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 4
- 238000005481 NMR spectroscopy Methods 0.000 description 4
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 4
- 238000001816 cooling Methods 0.000 description 4
- 239000013078 crystal Substances 0.000 description 4
- 238000010438 heat treatment Methods 0.000 description 4
- 238000007069 methylation reaction Methods 0.000 description 4
- 239000012044 organic layer Substances 0.000 description 4
- 239000000741 silica gel Substances 0.000 description 4
- 229910002027 silica gel Inorganic materials 0.000 description 4
- 239000000243 solution Substances 0.000 description 4
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 4
- 238000010626 work up procedure Methods 0.000 description 4
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- MTCFGRXMJLQNBG-UWTATZPHSA-N D-Serine Chemical compound OC[C@@H](N)C(O)=O MTCFGRXMJLQNBG-UWTATZPHSA-N 0.000 description 3
- 229930195711 D-Serine Natural products 0.000 description 3
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 3
- 230000009286 beneficial effect Effects 0.000 description 3
- 239000003054 catalyst Substances 0.000 description 3
- 239000000460 chlorine Substances 0.000 description 3
- 238000003776 cleavage reaction Methods 0.000 description 3
- 239000000463 material Substances 0.000 description 3
- 239000012452 mother liquor Substances 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 238000005086 pumping Methods 0.000 description 3
- 230000007017 scission Effects 0.000 description 3
- JTDGKQNNPKXKII-SSDOTTSWSA-N (1r)-1-(4-methoxyphenyl)ethanamine Chemical compound COC1=CC=C([C@@H](C)N)C=C1 JTDGKQNNPKXKII-SSDOTTSWSA-N 0.000 description 2
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 2
- 0 C*(N(*)[C@](COC)C(C)=O)O Chemical compound C*(N(*)[C@](COC)C(C)=O)O 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- 239000002202 Polyethylene glycol Substances 0.000 description 2
- UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical class [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 2
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
- 238000006640 acetylation reaction Methods 0.000 description 2
- 150000001298 alcohols Chemical class 0.000 description 2
- 238000004458 analytical method Methods 0.000 description 2
- 239000011260 aqueous acid Substances 0.000 description 2
- WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 229910052796 boron Inorganic materials 0.000 description 2
- 239000012267 brine Substances 0.000 description 2
- 229910052801 chlorine Inorganic materials 0.000 description 2
- ZZVUWRFHKOJYTH-UHFFFAOYSA-N diphenhydramine Chemical group C=1C=CC=CC=1C(OCCN(C)C)C1=CC=CC=C1 ZZVUWRFHKOJYTH-UHFFFAOYSA-N 0.000 description 2
- 238000001914 filtration Methods 0.000 description 2
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 2
- 229940011051 isopropyl acetate Drugs 0.000 description 2
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 2
- 239000010410 layer Substances 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- UZKWTJUDCOPSNM-UHFFFAOYSA-N methoxybenzene Substances CCCCOC=C UZKWTJUDCOPSNM-UHFFFAOYSA-N 0.000 description 2
- QSRRZKPKHJHIRB-UHFFFAOYSA-N methyl 4-[(2,5-dichloro-4-methylthiophen-3-yl)sulfonylamino]-2-hydroxybenzoate Chemical compound C1=C(O)C(C(=O)OC)=CC=C1NS(=O)(=O)C1=C(Cl)SC(Cl)=C1C QSRRZKPKHJHIRB-UHFFFAOYSA-N 0.000 description 2
- 229920001223 polyethylene glycol Polymers 0.000 description 2
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
- 239000000376 reactant Substances 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000011734 sodium Substances 0.000 description 2
- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 2
- 238000005406 washing Methods 0.000 description 2
- RQEUFEKYXDPUSK-ZETCQYMHSA-N (1S)-1-phenylethanamine Chemical compound C[C@H](N)C1=CC=CC=C1 RQEUFEKYXDPUSK-ZETCQYMHSA-N 0.000 description 1
- VENQOHAPVLVQKV-SSDOTTSWSA-N (1r)-1-(2-methoxyphenyl)ethanamine Chemical compound COC1=CC=CC=C1[C@@H](C)N VENQOHAPVLVQKV-SSDOTTSWSA-N 0.000 description 1
- JRZGPXSSNPTNMA-JTQLQIEISA-N (1s)-1,2,3,4-tetrahydronaphthalen-1-amine Chemical compound C1=CC=C2[C@@H](N)CCCC2=C1 JRZGPXSSNPTNMA-JTQLQIEISA-N 0.000 description 1
- JTDGKQNNPKXKII-ZETCQYMHSA-N (1s)-1-(4-methoxyphenyl)ethanamine Chemical compound COC1=CC=C([C@H](C)N)C=C1 JTDGKQNNPKXKII-ZETCQYMHSA-N 0.000 description 1
- RTCUCQWIICFPOD-VIFPVBQESA-N (1s)-1-naphthalen-1-ylethanamine Chemical compound C1=CC=C2C([C@@H](N)C)=CC=CC2=C1 RTCUCQWIICFPOD-VIFPVBQESA-N 0.000 description 1
- KHSYYLCXQKCYQX-VIFPVBQESA-N (1s)-1-naphthalen-2-ylethanamine Chemical compound C1=CC=CC2=CC([C@@H](N)C)=CC=C21 KHSYYLCXQKCYQX-VIFPVBQESA-N 0.000 description 1
- AQFLVLHRZFLDDV-VIFPVBQESA-N (1s)-1-phenylpropan-1-amine Chemical compound CC[C@H](N)C1=CC=CC=C1 AQFLVLHRZFLDDV-VIFPVBQESA-N 0.000 description 1
- XJEVHMGJSYVQBQ-VIFPVBQESA-N (1s)-2,3-dihydro-1h-inden-1-amine Chemical compound C1=CC=C2[C@@H](N)CCC2=C1 XJEVHMGJSYVQBQ-VIFPVBQESA-N 0.000 description 1
- WIWUIYDKJPYAEJ-OXQOHEQNSA-N (2r)-2-[acetyl-[(1r)-1-(2-methoxyphenyl)ethyl]amino]-n-benzyl-3-methoxypropanamide Chemical compound C1([C@@H](C)N([C@H](COC)C(=O)NCC=2C=CC=CC=2)C(C)=O)=CC=CC=C1OC WIWUIYDKJPYAEJ-OXQOHEQNSA-N 0.000 description 1
- CGSMTGRQCZHZHM-FCHUYYIVSA-N (2r)-2-[acetyl-[(1s)-1,2,3,4-tetrahydronaphthalen-1-yl]amino]-n-benzyl-3-methoxypropanamide Chemical compound O=C([C@H](N([C@@H]1C2=CC=CC=C2CCC1)C(C)=O)COC)NCC1=CC=CC=C1 CGSMTGRQCZHZHM-FCHUYYIVSA-N 0.000 description 1
- RAQLAEHVXVNAMF-MGPUTAFESA-N (2r)-2-[acetyl-[(1s)-1-(4-nitrophenyl)ethyl]amino]-n-benzyl-3-methoxypropanamide Chemical compound C1([C@H](C)N([C@H](COC)C(=O)NCC=2C=CC=CC=2)C(C)=O)=CC=C([N+]([O-])=O)C=C1 RAQLAEHVXVNAMF-MGPUTAFESA-N 0.000 description 1
- MEQFVONGAGDYCP-MHECFPHRSA-N (2r)-2-[acetyl-[(1s)-1-naphthalen-1-ylethyl]amino]-n-benzyl-3-methoxypropanamide Chemical compound O=C([C@H](N([C@@H](C)C=1C2=CC=CC=C2C=CC=1)C(C)=O)COC)NCC1=CC=CC=C1 MEQFVONGAGDYCP-MHECFPHRSA-N 0.000 description 1
- ZPHVTTAABNMOSC-MHECFPHRSA-N (2r)-2-[acetyl-[(1s)-1-naphthalen-2-ylethyl]amino]-n-benzyl-3-methoxypropanamide Chemical compound O=C([C@H](N([C@@H](C)C=1C=C2C=CC=CC2=CC=1)C(C)=O)COC)NCC1=CC=CC=C1 ZPHVTTAABNMOSC-MHECFPHRSA-N 0.000 description 1
- KWRHCCJQQNUOGC-OXJNMPFZSA-N (2r)-2-[acetyl-[(1s)-1-phenylethyl]amino]-n-benzyl-3-methoxypropanamide Chemical compound C1([C@H](C)N([C@H](COC)C(=O)NCC=2C=CC=CC=2)C(C)=O)=CC=CC=C1 KWRHCCJQQNUOGC-OXJNMPFZSA-N 0.000 description 1
- GRMUICBQZOJZOY-LEWJYISDSA-N (2r)-2-[acetyl-[(1s)-1-phenylpropyl]amino]-n-benzyl-3-methoxypropanamide Chemical compound O=C([C@@H](COC)N([C@@H](CC)C=1C=CC=CC=1)C(C)=O)NCC1=CC=CC=C1 GRMUICBQZOJZOY-LEWJYISDSA-N 0.000 description 1
- CSKGWQHEAODYGD-LEWJYISDSA-N (2r)-2-[acetyl-[(1s)-2,3-dihydro-1h-inden-1-yl]amino]-n-benzyl-3-methoxypropanamide Chemical compound O=C([C@H](N([C@@H]1C2=CC=CC=C2CC1)C(C)=O)COC)NCC1=CC=CC=C1 CSKGWQHEAODYGD-LEWJYISDSA-N 0.000 description 1
- CGUNDOJCNKEPAU-CAWMZFRYSA-N (2r)-2-[acetyl-[1-(4-methoxyphenyl)ethyl]amino]-n-benzyl-3-methoxypropanamide Chemical compound CC(=O)N([C@H](COC)C(=O)NCC=1C=CC=CC=1)C(C)C1=CC=C(OC)C=C1 CGUNDOJCNKEPAU-CAWMZFRYSA-N 0.000 description 1
- IDPURXSQCKYKIJ-UHFFFAOYSA-N 1-(4-methoxyphenyl)methanamine Chemical compound COC1=CC=C(CN)C=C1 IDPURXSQCKYKIJ-UHFFFAOYSA-N 0.000 description 1
- DEGFAGJDDMYMQK-UHFFFAOYSA-N 2-[acetyl(benzhydryl)amino]-n-benzyl-3-methoxypropanamide Chemical compound C=1C=CC=CC=1CNC(=O)C(COC)N(C(C)=O)C(C=1C=CC=CC=1)C1=CC=CC=C1 DEGFAGJDDMYMQK-UHFFFAOYSA-N 0.000 description 1
- OHTMGZJVLZCYLK-UHFFFAOYSA-N 2-[acetyl(benzyl)amino]-n-benzyl-3-methoxypropanamide Chemical compound C=1C=CC=CC=1CNC(=O)C(COC)N(C(C)=O)CC1=CC=CC=C1 OHTMGZJVLZCYLK-UHFFFAOYSA-N 0.000 description 1
- YFMPCTAOHWPGEQ-UHFFFAOYSA-N 2-[acetyl(trityl)amino]-n-benzyl-3-methoxypropanamide Chemical compound C=1C=CC=CC=1CNC(=O)C(COC)N(C(C)=O)C(C=1C=CC=CC=1)(C=1C=CC=CC=1)C1=CC=CC=C1 YFMPCTAOHWPGEQ-UHFFFAOYSA-N 0.000 description 1
- QVBCFWQQWZRPIS-UHFFFAOYSA-N 2-[acetyl-[(4-methoxyphenyl)methyl]amino]-n-benzyl-3-methoxypropanamide Chemical compound C=1C=CC=CC=1CNC(=O)C(COC)N(C(C)=O)CC1=CC=C(OC)C=C1 QVBCFWQQWZRPIS-UHFFFAOYSA-N 0.000 description 1
- QCQCHGYLTSGIGX-GHXANHINSA-N 4-[[(3ar,5ar,5br,7ar,9s,11ar,11br,13as)-5a,5b,8,8,11a-pentamethyl-3a-[(5-methylpyridine-3-carbonyl)amino]-2-oxo-1-propan-2-yl-4,5,6,7,7a,9,10,11,11b,12,13,13a-dodecahydro-3h-cyclopenta[a]chrysen-9-yl]oxy]-2,2-dimethyl-4-oxobutanoic acid Chemical compound N([C@@]12CC[C@@]3(C)[C@]4(C)CC[C@H]5C(C)(C)[C@@H](OC(=O)CC(C)(C)C(O)=O)CC[C@]5(C)[C@H]4CC[C@@H]3C1=C(C(C2)=O)C(C)C)C(=O)C1=CN=CC(C)=C1 QCQCHGYLTSGIGX-GHXANHINSA-N 0.000 description 1
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 1
- GMLJQHNLDHDNPX-UHFFFAOYSA-N CNC(COC)C(OC)=O Chemical compound CNC(COC)C(OC)=O GMLJQHNLDHDNPX-UHFFFAOYSA-N 0.000 description 1
- PSFABYLDRXJYID-GSVOUGTGSA-N CN[C@H](CO)C(O)=O Chemical compound CN[C@H](CO)C(O)=O PSFABYLDRXJYID-GSVOUGTGSA-N 0.000 description 1
- WPLANNRKFDHEKD-SNVBAGLBSA-N COC[C@H](C(NCc1ccccc1)=O)N Chemical compound COC[C@H](C(NCc1ccccc1)=O)N WPLANNRKFDHEKD-SNVBAGLBSA-N 0.000 description 1
- DRSHXJFUUPIBHX-UHFFFAOYSA-N COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 Chemical compound COc1ccc(cc1)N1N=CC2C=NC(Nc3cc(OC)c(OC)c(OCCCN4CCN(C)CC4)c3)=NC12 DRSHXJFUUPIBHX-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 description 1
- 206010010904 Convulsion Diseases 0.000 description 1
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 1
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 1
- CZQQGVFHLSBEDV-RGMNGODLSA-N [(1s)-1-(4-nitrophenyl)ethyl]azanium;chloride Chemical compound Cl.C[C@H](N)C1=CC=C([N+]([O-])=O)C=C1 CZQQGVFHLSBEDV-RGMNGODLSA-N 0.000 description 1
- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
- 230000004913 activation Effects 0.000 description 1
- 239000000654 additive Substances 0.000 description 1
- 125000000217 alkyl group Chemical group 0.000 description 1
- 150000001408 amides Chemical class 0.000 description 1
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 description 1
- 230000001773 anti-convulsant effect Effects 0.000 description 1
- 239000001961 anticonvulsive agent Substances 0.000 description 1
- 229960003965 antiepileptics Drugs 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 238000010923 batch production Methods 0.000 description 1
- JPYQFYIEOUVJDU-UHFFFAOYSA-N beclamide Chemical compound ClCCC(=O)NCC1=CC=CC=C1 JPYQFYIEOUVJDU-UHFFFAOYSA-N 0.000 description 1
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 1
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 1
- 229910052794 bromium Inorganic materials 0.000 description 1
- 239000006227 byproduct Substances 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- 230000008859 change Effects 0.000 description 1
- 238000001311 chemical methods and process Methods 0.000 description 1
- 238000013375 chromatographic separation Methods 0.000 description 1
- 238000010924 continuous production Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 230000001419 dependent effect Effects 0.000 description 1
- 238000010511 deprotection reaction Methods 0.000 description 1
- VAYGXNSJCAHWJZ-UHFFFAOYSA-N dimethyl sulfate Chemical compound COS(=O)(=O)OC VAYGXNSJCAHWJZ-UHFFFAOYSA-N 0.000 description 1
- MGHPNCMVUAKAIE-UHFFFAOYSA-N diphenylmethanamine Chemical compound C=1C=CC=CC=1C(N)C1=CC=CC=C1 MGHPNCMVUAKAIE-UHFFFAOYSA-N 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- 229940079593 drug Drugs 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 238000003821 enantio-separation Methods 0.000 description 1
- 238000010931 ester hydrolysis Methods 0.000 description 1
- 150000002148 esters Chemical class 0.000 description 1
- OCLXJTCGWSSVOE-UHFFFAOYSA-N ethanol etoh Chemical compound CCO.CCO OCLXJTCGWSSVOE-UHFFFAOYSA-N 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 229910052731 fluorine Inorganic materials 0.000 description 1
- 125000001153 fluoro group Chemical group F* 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 238000005984 hydrogenation reaction Methods 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 229910052500 inorganic mineral Inorganic materials 0.000 description 1
- QWXYZCJEXYQNEI-OSZHWHEXSA-N intermediate I Chemical compound COC(=O)[C@@]1(C=O)[C@H]2CC=[N+](C\C2=C\C)CCc2c1[nH]c1ccccc21 QWXYZCJEXYQNEI-OSZHWHEXSA-N 0.000 description 1
- 229910052740 iodine Inorganic materials 0.000 description 1
- 125000002346 iodo group Chemical group I* 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 150000002527 isonitriles Chemical class 0.000 description 1
- COTNUBDHGSIOTA-UHFFFAOYSA-N meoh methanol Chemical compound OC.OC COTNUBDHGSIOTA-UHFFFAOYSA-N 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 229940043265 methyl isobutyl ketone Drugs 0.000 description 1
- 239000011707 mineral Substances 0.000 description 1
- 235000010755 mineral Nutrition 0.000 description 1
- 230000007935 neutral effect Effects 0.000 description 1
- 238000006386 neutralization reaction Methods 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 150000007524 organic acids Chemical class 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 description 1
- 239000003880 polar aprotic solvent Substances 0.000 description 1
- 238000002360 preparation method Methods 0.000 description 1
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 1
- 239000003586 protic polar solvent Substances 0.000 description 1
- 238000000746 purification Methods 0.000 description 1
- 238000004007 reversed phase HPLC Methods 0.000 description 1
- 238000010898 silica gel chromatography Methods 0.000 description 1
- 239000011877 solvent mixture Substances 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 150000003512 tertiary amines Chemical class 0.000 description 1
- WHRNULOCNSKMGB-UHFFFAOYSA-N tetrahydrofuran thf Chemical compound C1CCOC1.C1CCOC1 WHRNULOCNSKMGB-UHFFFAOYSA-N 0.000 description 1
- 125000001412 tetrahydropyranyl group Chemical group 0.000 description 1
- WROMPOXWARCANT-UHFFFAOYSA-N tfa trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.OC(=O)C(F)(F)F WROMPOXWARCANT-UHFFFAOYSA-N 0.000 description 1
- BZVJOYBTLHNRDW-UHFFFAOYSA-N triphenylmethanamine Chemical compound C=1C=CC=CC=1C(C=1C=CC=CC=1)(N)C1=CC=CC=C1 BZVJOYBTLHNRDW-UHFFFAOYSA-N 0.000 description 1
- 239000008096 xylene Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C237/00—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups
- C07C237/02—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton
- C07C237/22—Carboxylic acid amides, the carbon skeleton of the acid part being further substituted by amino groups having the carbon atoms of the carboxamide groups bound to acyclic carbon atoms of the carbon skeleton having nitrogen atoms of amino groups bound to the carbon skeleton of the acid part, further acylated
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/12—Preparation of carboxylic acid amides by reactions not involving the formation of carboxamide groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C231/00—Preparation of carboxylic acid amides
- C07C231/16—Preparation of optical isomers
- C07C231/18—Preparation of optical isomers by stereospecific synthesis
-
- 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)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP11009048.7 | 2011-11-15 | ||
| EP11009048 | 2011-11-15 | ||
| PCT/EP2012/072548 WO2013072330A1 (en) | 2011-11-15 | 2012-11-14 | Process for the production of n-substituted 2-(acetylamino)-n'-benzyl-3-methoxypropanamides |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2014533292A true JP2014533292A (ja) | 2014-12-11 |
Family
ID=47178026
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP2014541630A Pending JP2014533292A (ja) | 2011-11-15 | 2012-11-14 | Ｎ−置換された２−（アセチルアミノ）−ｎ’−ベンジル−３−メトキシプロパンアミドの製造方法 |
Country Status (10)
| Country | Link |
|---|---|
| EP (1) | EP2780318B1 (enExample) |
| JP (1) | JP2014533292A (enExample) |
| CN (1) | CN103930397B (enExample) |
| BR (1) | BR112014011748A2 (enExample) |
| EA (1) | EA024260B8 (enExample) |
| IL (1) | IL232627A0 (enExample) |
| IN (1) | IN2014KN01247A (enExample) |
| MX (1) | MX341754B (enExample) |
| WO (1) | WO2013072330A1 (enExample) |
| ZA (1) | ZA201403237B (enExample) |
Families Citing this family (2)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JPWO2016039393A1 (ja) * | 2014-09-10 | 2017-06-22 | 株式会社エーピーアイ コーポレーション | アミノ酸誘導体の製造方法 |
| CN117964512B (zh) * | 2024-04-01 | 2024-06-04 | 山东惟普控股有限公司 | 一种n,n-二甲基-3-甲氧基丙酰胺的合成方法 |
Family Cites Families (7)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE69311129T2 (de) | 1992-11-05 | 1997-09-18 | Dompe Farmaceutici Spa | Tartronsäure, deren acetalische äther und-o-ester |
| DE4425466A1 (de) | 1994-07-19 | 1996-01-25 | Thomas & Betts Gmbh | Kabel-Steckverbinder |
| EP1642889A1 (en) | 2004-10-02 | 2006-04-05 | Schwarz Pharma Ag | Improved synthesis scheme for lacosamide |
| US8093426B2 (en) * | 2007-12-04 | 2012-01-10 | Ranbaxy Laboratories Limited | Intermediate compounds and their use in preparation of lacosamide |
| US20100240926A1 (en) | 2009-03-18 | 2010-09-23 | Pliva Hrvatska D.O.O. | Process for preparing (r)-n-benzyl-2-(benyloxycarbonylamino)-3-methoxypropionamide |
| EP2462094B1 (en) | 2009-08-06 | 2016-12-21 | Shell Internationale Research Maatschappij B.V. | Process for preparing an alkylate |
| JP5564570B2 (ja) | 2009-09-25 | 2014-07-30 | カディラ・ヘルスケア・リミテッド | ラコサミドおよびその中間体の調製方法 |
-
2012
- 2012-11-14 CN CN201280056152.2A patent/CN103930397B/zh active Active
- 2012-11-14 WO PCT/EP2012/072548 patent/WO2013072330A1/en not_active Ceased
- 2012-11-14 MX MX2014005593A patent/MX341754B/es active IP Right Grant
- 2012-11-14 IN IN1247KON2014 patent/IN2014KN01247A/en unknown
- 2012-11-14 BR BR112014011748A patent/BR112014011748A2/pt not_active Application Discontinuation
- 2012-11-14 EA EA201490990A patent/EA024260B8/ru not_active IP Right Cessation
- 2012-11-14 JP JP2014541630A patent/JP2014533292A/ja active Pending
- 2012-11-14 EP EP12784603.8A patent/EP2780318B1/en active Active
-
2014
- 2014-05-05 ZA ZA2014/03237A patent/ZA201403237B/en unknown
- 2014-05-14 IL IL232627A patent/IL232627A0/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| BR112014011748A2 (pt) | 2017-05-30 |
| IL232627A0 (en) | 2014-06-30 |
| EA024260B1 (ru) | 2016-08-31 |
| WO2013072330A1 (en) | 2013-05-23 |
| EA024260B8 (ru) | 2016-11-30 |
| CN103930397B (zh) | 2015-10-21 |
| EA201490990A1 (ru) | 2014-11-28 |
| EP2780318B1 (en) | 2015-08-26 |
| CN103930397A (zh) | 2014-07-16 |
| EP2780318A1 (en) | 2014-09-24 |
| MX2014005593A (es) | 2015-01-22 |
| ZA201403237B (en) | 2015-12-23 |
| MX341754B (es) | 2016-09-02 |
| IN2014KN01247A (enExample) | 2015-10-16 |
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