JP2012513381A5 - - Google Patents

Info

Publication number

JP2012513381A5

JP2012513381A5 JP2011541509A JP2011541509A JP2012513381A5 JP 2012513381 A5 JP2012513381 A5 JP 2012513381A5 JP 2011541509 A JP2011541509 A JP 2011541509A JP 2011541509 A JP2011541509 A JP 2011541509A JP 2012513381 A5 JP2012513381 A5 JP 2012513381A5

Authority

JP

Japan

Prior art keywords

compound

formula

solvent

xxa

salt

Prior art date

2009-12-22

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.)

Granted

Links

• Espacenet
• Global Dossier
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• 238000000034 method Methods 0.000 claims 19
• 150000001875 compounds Chemical class 0.000 claims 16
• KMPWYEUPVWOPIM-KODHJQJWSA-N cinchonidine Chemical class C1=CC=C2C([C@H]([C@H]3[N@]4CC[C@H]([C@H](C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-KODHJQJWSA-N 0.000 claims 11
• 239000002904 solvent Substances 0.000 claims 9
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims 7
• -1 bicyclic lactone amide Chemical class 0.000 claims 7
• 150000003839 salts Chemical class 0.000 claims 7
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims 6
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims 6
• 238000004519 manufacturing process Methods 0.000 claims 5
• 239000000203 mixture Substances 0.000 claims 5
• LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims 4
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 claims 4
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims 4
• 238000006243 chemical reaction Methods 0.000 claims 4
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims 3
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims 3
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 claims 3
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims 3
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 claims 3
• KMPWYEUPVWOPIM-UHFFFAOYSA-N cinchonidine Natural products C1=CC=C2C(C(C3N4CCC(C(C4)C=C)C3)O)=CC=NC2=C1 KMPWYEUPVWOPIM-UHFFFAOYSA-N 0.000 claims 3
• 238000002360 preparation method Methods 0.000 claims 3
• 239000011877 solvent mixture Substances 0.000 claims 3
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims 3
• JWUJQDFVADABEY-UHFFFAOYSA-N 2-methyltetrahydrofuran Chemical compound CC1CCCO1 JWUJQDFVADABEY-UHFFFAOYSA-N 0.000 claims 2
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims 2
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 claims 2
• GKQLYSROISKDLL-UHFFFAOYSA-N EEDQ Chemical compound C1=CC=C2N(C(=O)OCC)C(OCC)C=CC2=C1 GKQLYSROISKDLL-UHFFFAOYSA-N 0.000 claims 2
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims 2
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 claims 2
• 238000010640 amide synthesis reaction Methods 0.000 claims 2
• 150000001408 amides Chemical class 0.000 claims 2
• 238000001953 recrystallisation Methods 0.000 claims 2
• 239000000725 suspension Substances 0.000 claims 2
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims 2
• BDNKZNFMNDZQMI-UHFFFAOYSA-N 1,3-diisopropylcarbodiimide Chemical compound CC(C)N=C=NC(C)C BDNKZNFMNDZQMI-UHFFFAOYSA-N 0.000 claims 1
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 claims 1
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims 1
• CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims 1
• 150000001298 alcohols Chemical class 0.000 claims 1
• 125000000217 alkyl group Chemical group 0.000 claims 1
• 239000000010 aprotic solvent Substances 0.000 claims 1
• 230000015572 biosynthetic process Effects 0.000 claims 1
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 claims 1
• 239000003054 catalyst Substances 0.000 claims 1
• 238000001816 cooling Methods 0.000 claims 1
• 239000007822 coupling agent Substances 0.000 claims 1
• 238000002425 crystallisation Methods 0.000 claims 1
• 230000008025 crystallization Effects 0.000 claims 1
• 239000003759 ester based solvent Substances 0.000 claims 1
• 150000002170 ethers Chemical class 0.000 claims 1
• 238000005755 formation reaction Methods 0.000 claims 1
• 150000008282 halocarbons Chemical class 0.000 claims 1
• 229930195733 hydrocarbon Natural products 0.000 claims 1
• 150000002430 hydrocarbons Chemical class 0.000 claims 1
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 claims 1
• 125000000686 lactone group Chemical group 0.000 claims 1
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
• QLSTWGZDXAHREY-UHFFFAOYSA-N n-methylhex-1-en-1-amine Chemical compound CCCCC=CNC QLSTWGZDXAHREY-UHFFFAOYSA-N 0.000 claims 1
• UGLYZKRVGNAOLZ-UHFFFAOYSA-N propan-2-yl 2-propan-2-yloxy-2h-quinoline-1-carboxylate Chemical compound C1=CC=C2N(C(=O)OC(C)C)C(OC(C)C)C=CC2=C1 UGLYZKRVGNAOLZ-UHFFFAOYSA-N 0.000 claims 1
• PNGLEYLFMHGIQO-UHFFFAOYSA-M sodium;3-(n-ethyl-3-methoxyanilino)-2-hydroxypropane-1-sulfonate;dihydrate Chemical compound O.O.[Na+].[O-]S(=O)(=O)CC(O)CN(CC)C1=CC=CC(OC)=C1 PNGLEYLFMHGIQO-UHFFFAOYSA-M 0.000 claims 1
• 150000003512 tertiary amines Chemical class 0.000 claims 1
• 125000005500 uronium group Chemical group 0.000 claims 1
• 239000008096 xylene Substances 0.000 claims 1
• 0 C=CC1*(CC2)CC(C3(CC3)c3ccnc4ccccc34)N2C1 Chemical compound C=CC1*(CC2)CC(C3(CC3)c3ccnc4ccccc34)N2C1 0.000 description 11
• YWHQIVJPIBHBSV-UHFFFAOYSA-N OC(C(CC(C1)O2)C1C2=O)=O Chemical compound OC(C(CC(C1)O2)C1C2=O)=O YWHQIVJPIBHBSV-UHFFFAOYSA-N 0.000 description 3
• JTZZSQYMACOLNN-VDWJNHBNSA-N CC(C)c1c[s]c(-c2cc(O[C@H](C[C@H]3C(N[C@](C4)([C@@H]4/C=C\CCCCN4C)C(NS(C5CC5)(=O)=O)=O)=O)C[C@H]3C4=O)c(ccc(OC)c3C)c3n2)n1 Chemical compound CC(C)c1c[s]c(-c2cc(O[C@H](C[C@H]3C(N[C@](C4)([C@@H]4/C=C\CCCCN4C)C(NS(C5CC5)(=O)=O)=O)=O)C[C@H]3C4=O)c(ccc(OC)c3C)c3n2)n1 JTZZSQYMACOLNN-VDWJNHBNSA-N 0.000 description 2
• KMPWYEUPVWOPIM-NAHPKXJFSA-N C=CC1C(CC2)CC([C@@H](c3c(cccc4)c4ncc3)O)N2C1 Chemical compound C=CC1C(CC2)CC([C@@H](c3c(cccc4)c4ncc3)O)N2C1 KMPWYEUPVWOPIM-NAHPKXJFSA-N 0.000 description 1
• XQOBFRSIHBMNMC-PLGQPLIWSA-N CC(C)c1c[s]c(-c2cc(O[C@H](C[C@H]3C(N[C@](C4)([C@@H]4/C=C\CCCCN4C)C(O)=O)=O)C[C@H]3C4=O)c(ccc(OC)c3C)c3n2)n1 Chemical compound CC(C)c1c[s]c(-c2cc(O[C@H](C[C@H]3C(N[C@](C4)([C@@H]4/C=C\CCCCN4C)C(O)=O)=O)C[C@H]3C4=O)c(ccc(OC)c3C)c3n2)n1 XQOBFRSIHBMNMC-PLGQPLIWSA-N 0.000 description 1
• KKEQTCOFLWKZOY-MDNUFGMLSA-N CC(C)c1c[s]c(-c2nc(c(C)c(cc3)OC)c3c(O[C@@H](C[C@H]3C(N(C)CCCCC=C)=O)C[C@H]3C(O)=O)c2)n1 Chemical compound CC(C)c1c[s]c(-c2nc(c(C)c(cc3)OC)c3c(O[C@@H](C[C@H]3C(N(C)CCCCC=C)=O)C[C@H]3C(O)=O)c2)n1 KKEQTCOFLWKZOY-MDNUFGMLSA-N 0.000 description 1
• UTIOQBMMOGSBEA-IJWPFNNMSA-N CC(C1)C=Cc2c1c([C@H](C(CC1CC3)N3CC1C=C)O)ccn2 Chemical compound CC(C1)C=Cc2c1c([C@H](C(CC1CC3)N3CC1C=C)O)ccn2 UTIOQBMMOGSBEA-IJWPFNNMSA-N 0.000 description 1
• SEKCMPWEKHOBBR-UHFFFAOYSA-N CN(CCCCC=C)C(C(CC(C1)O2)C1C2=O)=O Chemical compound CN(CCCCC=C)C(C(CC(C1)O2)C1C2=O)=O SEKCMPWEKHOBBR-UHFFFAOYSA-N 0.000 description 1