KR20110098964A - 수소화 전이반응을 사용한 광학 활성 화합물의 제조 방법 - Google Patents
수소화 전이반응을 사용한 광학 활성 화합물의 제조 방법 Download PDFInfo
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- KR20110098964A KR20110098964A KR1020117017258A KR20117017258A KR20110098964A KR 20110098964 A KR20110098964 A KR 20110098964A KR 1020117017258 A KR1020117017258 A KR 1020117017258A KR 20117017258 A KR20117017258 A KR 20117017258A KR 20110098964 A KR20110098964 A KR 20110098964A
- Authority
- KR
- South Korea
- Prior art keywords
- ethyl
- phenol
- compound
- hydroxy
- formula
- 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.)
- Ceased
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- 150000001875 compounds Chemical class 0.000 title claims abstract description 78
- 238000000034 method Methods 0.000 title claims abstract description 59
- 238000006276 transfer reaction Methods 0.000 title claims abstract description 28
- 238000005984 hydrogenation reaction Methods 0.000 title claims description 27
- GQZXRLWUYONVCP-QMMMGPOBSA-N 3-[(1s)-1-(dimethylamino)ethyl]phenol Chemical compound CN(C)[C@@H](C)C1=CC=CC(O)=C1 GQZXRLWUYONVCP-QMMMGPOBSA-N 0.000 claims abstract description 53
- 238000010531 catalytic reduction reaction Methods 0.000 claims abstract description 26
- XSVMFMHYUFZWBK-NSHDSACASA-N Rivastigmine Chemical compound CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 XSVMFMHYUFZWBK-NSHDSACASA-N 0.000 claims abstract description 25
- 229960004136 rivastigmine Drugs 0.000 claims abstract description 20
- 238000002360 preparation method Methods 0.000 claims abstract description 19
- FEWJPZIEWOKRBE-JCYAYHJZSA-M L-tartrate(1-) Chemical compound OC(=O)[C@H](O)[C@@H](O)C([O-])=O FEWJPZIEWOKRBE-JCYAYHJZSA-M 0.000 claims abstract description 11
- 239000003054 catalyst Substances 0.000 claims description 46
- COJRWHSKVYUZHQ-ZCFIWIBFSA-N 3-[(1r)-1-hydroxyethyl]phenol Chemical compound C[C@@H](O)C1=CC=CC(O)=C1 COJRWHSKVYUZHQ-ZCFIWIBFSA-N 0.000 claims description 42
- LUJMEECXHPYQOF-UHFFFAOYSA-N 3-hydroxyacetophenone Chemical compound CC(=O)C1=CC=CC(O)=C1 LUJMEECXHPYQOF-UHFFFAOYSA-N 0.000 claims description 39
- 239000000203 mixture Substances 0.000 claims description 36
- 150000003839 salts Chemical class 0.000 claims description 34
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 31
- 239000000047 product Substances 0.000 claims description 31
- -1 halide compounds Chemical class 0.000 claims description 27
- 229910052751 metal Inorganic materials 0.000 claims description 25
- 239000002184 metal Substances 0.000 claims description 25
- 230000008569 process Effects 0.000 claims description 25
- ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 claims description 23
- ISWSIDIOOBJBQZ-UHFFFAOYSA-N phenol group Chemical group C1(=CC=CC=C1)O ISWSIDIOOBJBQZ-UHFFFAOYSA-N 0.000 claims description 23
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 21
- 238000002425 crystallisation Methods 0.000 claims description 20
- 230000008025 crystallization Effects 0.000 claims description 20
- 230000001476 alcoholic effect Effects 0.000 claims description 19
- 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 18
- 229910052723 transition metal Inorganic materials 0.000 claims description 17
- 150000003624 transition metals Chemical class 0.000 claims description 17
- 125000003118 aryl group Chemical group 0.000 claims description 16
- 238000004519 manufacturing process Methods 0.000 claims description 15
- 238000010534 nucleophilic substitution reaction Methods 0.000 claims description 14
- 239000002253 acid Substances 0.000 claims description 13
- 239000003795 chemical substances by application Substances 0.000 claims description 13
- 150000004820 halides Chemical class 0.000 claims description 13
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 12
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- 230000003213 activating effect Effects 0.000 claims description 10
- 150000001412 amines Chemical class 0.000 claims description 10
- NLFBCYMMUAKCPC-KQQUZDAGSA-N ethyl (e)-3-[3-amino-2-cyano-1-[(e)-3-ethoxy-3-oxoprop-1-enyl]sulfanyl-3-oxoprop-1-enyl]sulfanylprop-2-enoate Chemical compound CCOC(=O)\C=C\SC(=C(C#N)C(N)=O)S\C=C\C(=O)OCC NLFBCYMMUAKCPC-KQQUZDAGSA-N 0.000 claims description 10
- 239000012458 free base Substances 0.000 claims description 10
- 239000008194 pharmaceutical composition Substances 0.000 claims description 10
- FKLJPTJMIBLJAV-UHFFFAOYSA-N Compound IV Chemical compound O1N=C(C)C=C1CCCCCCCOC1=CC=C(C=2OCCN=2)C=C1 FKLJPTJMIBLJAV-UHFFFAOYSA-N 0.000 claims description 9
- 150000001414 amino alcohols Chemical class 0.000 claims description 9
- 125000006649 (C2-C20) alkynyl group Chemical group 0.000 claims description 8
- 125000003358 C2-C20 alkenyl group Chemical group 0.000 claims description 8
- HFPZCAJZSCWRBC-UHFFFAOYSA-N p-cymene Chemical compound CC(C)C1=CC=C(C)C=C1 HFPZCAJZSCWRBC-UHFFFAOYSA-N 0.000 claims description 8
- 230000004913 activation Effects 0.000 claims description 7
- 229910052707 ruthenium Inorganic materials 0.000 claims description 7
- XYFCBTPGUUZFHI-UHFFFAOYSA-N Phosphine Chemical compound P XYFCBTPGUUZFHI-UHFFFAOYSA-N 0.000 claims description 6
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- 238000012377 drug delivery Methods 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 claims description 6
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 claims description 5
- CZCQMRZQDWWULM-VIFPVBQESA-N [3-[(1s)-1-(dimethylamino)ethyl]phenyl] methanesulfonate Chemical compound CN(C)[C@@H](C)C1=CC=CC(OS(C)(=O)=O)=C1 CZCQMRZQDWWULM-VIFPVBQESA-N 0.000 claims description 5
- 229910052741 iridium Inorganic materials 0.000 claims description 5
- 239000003446 ligand Substances 0.000 claims description 5
- 229910052703 rhodium Inorganic materials 0.000 claims description 5
- BDHFUVZGWQCTTF-UHFFFAOYSA-M sulfonate Chemical compound [O-]S(=O)=O BDHFUVZGWQCTTF-UHFFFAOYSA-M 0.000 claims description 5
- CLPXHEDITUKVCC-UHFFFAOYSA-K 1-methyl-4-propan-2-ylbenzene;trichlororuthenium Chemical class Cl[Ru](Cl)Cl.CC(C)C1=CC=C(C)C=C1 CLPXHEDITUKVCC-UHFFFAOYSA-K 0.000 claims description 4
- 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 4
- WAPZHQZXWPVDMP-MRVPVSSYSA-N [3-[(1r)-1-methylsulfonyloxyethyl]phenyl] methanesulfonate Chemical compound CS(=O)(=O)O[C@H](C)C1=CC=CC(OS(C)(=O)=O)=C1 WAPZHQZXWPVDMP-MRVPVSSYSA-N 0.000 claims description 4
- 125000003368 amide group Chemical group 0.000 claims description 4
- 150000001408 amides Chemical class 0.000 claims description 4
- XMBWDFGMSWQBCA-UHFFFAOYSA-N hydrogen iodide Chemical compound I XMBWDFGMSWQBCA-UHFFFAOYSA-N 0.000 claims description 4
- 229940098779 methanesulfonic acid Drugs 0.000 claims description 4
- RRKODOZNUZCUBN-CCAGOZQPSA-N (1z,3z)-cycloocta-1,3-diene Chemical compound C1CC\C=C/C=C\C1 RRKODOZNUZCUBN-CCAGOZQPSA-N 0.000 claims description 3
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 3
- UGFAIRIUMAVXCW-UHFFFAOYSA-N Carbon monoxide Chemical compound [O+]#[C-] UGFAIRIUMAVXCW-UHFFFAOYSA-N 0.000 claims description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 claims description 3
- 125000005595 acetylacetonate group Chemical group 0.000 claims description 3
- 229940125363 active pharmaceutical ingredient starting material Drugs 0.000 claims description 3
- 239000012566 active pharmaceutical ingredient starting material Substances 0.000 claims description 3
- 229910002091 carbon monoxide Inorganic materials 0.000 claims description 3
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
- 150000008282 halocarbons Chemical class 0.000 claims description 3
- HZVOZRGWRWCICA-UHFFFAOYSA-N methanediyl Chemical compound [CH2] HZVOZRGWRWCICA-UHFFFAOYSA-N 0.000 claims description 3
- UOPFIWYXBIHPIP-NHCUHLMSSA-N n-[(1r,2r)-2-amino-1,2-diphenylethyl]-4-methylbenzenesulfonamide Chemical compound C1=CC(C)=CC=C1S(=O)(=O)N[C@H](C=1C=CC=CC=1)[C@H](N)C1=CC=CC=C1 UOPFIWYXBIHPIP-NHCUHLMSSA-N 0.000 claims description 3
- 150000002825 nitriles Chemical class 0.000 claims description 3
- SJYNFBVQFBRSIB-UHFFFAOYSA-N norbornadiene Chemical compound C1=CC2C=CC1C2 SJYNFBVQFBRSIB-UHFFFAOYSA-N 0.000 claims description 3
- 229910000073 phosphorus hydride Inorganic materials 0.000 claims description 3
- 239000000651 prodrug Substances 0.000 claims description 3
- 229940002612 prodrug Drugs 0.000 claims description 3
- 230000006103 sulfonylation Effects 0.000 claims description 3
- 238000005694 sulfonylation reaction Methods 0.000 claims description 3
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 claims description 3
- KORBNZMNKRINHE-SSDOTTSWSA-N [(1r)-1-(3-hydroxyphenyl)ethyl] methanesulfonate Chemical compound CS(=O)(=O)O[C@H](C)C1=CC=CC(O)=C1 KORBNZMNKRINHE-SSDOTTSWSA-N 0.000 claims description 2
- FRQAHZNIOOIVSU-SSDOTTSWSA-N [3-[(1r)-1-hydroxyethyl]phenyl] methanesulfonate Chemical compound C[C@@H](O)C1=CC=CC(OS(C)(=O)=O)=C1 FRQAHZNIOOIVSU-SSDOTTSWSA-N 0.000 claims description 2
- 125000000304 alkynyl group Chemical group 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
- 230000000536 complexating effect Effects 0.000 claims description 2
- PONXTPCRRASWKW-KBPBESRZSA-N diphenylethylenediamine Chemical compound C1([C@H](N)[C@@H](N)C=2C=CC=CC=2)=CC=CC=C1 PONXTPCRRASWKW-KBPBESRZSA-N 0.000 claims description 2
- 239000012467 final product Substances 0.000 claims description 2
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
- 125000004066 1-hydroxyethyl group Chemical group [H]OC([H])([*])C([H])([H])[H] 0.000 claims 1
- KORBNZMNKRINHE-ZETCQYMHSA-N [(1s)-1-(3-hydroxyphenyl)ethyl] methanesulfonate Chemical compound CS(=O)(=O)O[C@@H](C)C1=CC=CC(O)=C1 KORBNZMNKRINHE-ZETCQYMHSA-N 0.000 claims 1
- CZCQMRZQDWWULM-SECBINFHSA-N [3-[(1r)-1-(dimethylamino)ethyl]phenyl] methanesulfonate Chemical compound CN(C)[C@H](C)C1=CC=CC(OS(C)(=O)=O)=C1 CZCQMRZQDWWULM-SECBINFHSA-N 0.000 claims 1
- FRQAHZNIOOIVSU-ZETCQYMHSA-N [3-[(1s)-1-hydroxyethyl]phenyl] methanesulfonate Chemical compound C[C@H](O)C1=CC=CC(OS(C)(=O)=O)=C1 FRQAHZNIOOIVSU-ZETCQYMHSA-N 0.000 claims 1
- WAPZHQZXWPVDMP-QMMMGPOBSA-N [3-[(1s)-1-methylsulfonyloxyethyl]phenyl] methanesulfonate Chemical compound CS(=O)(=O)O[C@@H](C)C1=CC=CC(OS(C)(=O)=O)=C1 WAPZHQZXWPVDMP-QMMMGPOBSA-N 0.000 claims 1
- 238000006243 chemical reaction Methods 0.000 abstract description 19
- 239000008186 active pharmaceutical agent Substances 0.000 abstract description 7
- 229940088679 drug related substance Drugs 0.000 abstract description 6
- 230000003197 catalytic effect Effects 0.000 abstract description 4
- 238000009903 catalytic hydrogenation reaction Methods 0.000 abstract description 4
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 72
- 239000000243 solution Substances 0.000 description 29
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 25
- 239000002904 solvent Substances 0.000 description 25
- 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 22
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 18
- 239000013078 crystal Substances 0.000 description 18
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 17
- 230000010933 acylation Effects 0.000 description 15
- 238000005917 acylation reaction Methods 0.000 description 15
- 230000015572 biosynthetic process Effects 0.000 description 15
- 238000003756 stirring Methods 0.000 description 15
- 239000002585 base Substances 0.000 description 13
- 239000000725 suspension Substances 0.000 description 13
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 13
- 150000008064 anhydrides Chemical class 0.000 description 11
- 150000002009 diols Chemical class 0.000 description 11
- 239000012071 phase Substances 0.000 description 11
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 9
- 229940093499 ethyl acetate Drugs 0.000 description 9
- 239000008346 aqueous phase Substances 0.000 description 8
- 229920005862 polyol Polymers 0.000 description 8
- 150000003077 polyols Chemical class 0.000 description 8
- 230000000269 nucleophilic effect Effects 0.000 description 7
- 239000007858 starting material Substances 0.000 description 7
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 7
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 6
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
- 238000006555 catalytic reaction Methods 0.000 description 6
- 238000004821 distillation Methods 0.000 description 6
- CZCQMRZQDWWULM-UHFFFAOYSA-N [3-[1-(dimethylamino)ethyl]phenyl] methanesulfonate Chemical compound CN(C)C(C)C1=CC=CC(OS(C)(=O)=O)=C1 CZCQMRZQDWWULM-UHFFFAOYSA-N 0.000 description 5
- 239000002775 capsule Substances 0.000 description 5
- 238000001816 cooling Methods 0.000 description 5
- 239000007787 solid Substances 0.000 description 5
- KORBNZMNKRINHE-UHFFFAOYSA-N 1-(3-hydroxyphenyl)ethyl methanesulfonate Chemical compound CS(=O)(=O)OC(C)C1=CC=CC(O)=C1 KORBNZMNKRINHE-UHFFFAOYSA-N 0.000 description 4
- GQZXRLWUYONVCP-UHFFFAOYSA-N 3-[1-(dimethylamino)ethyl]phenol Chemical compound CN(C)C(C)C1=CC=CC(O)=C1 GQZXRLWUYONVCP-UHFFFAOYSA-N 0.000 description 4
- 208000024827 Alzheimer disease Diseases 0.000 description 4
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- BDAGIHXWWSANSR-UHFFFAOYSA-N Formic acid Chemical compound OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 4
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 4
- FRQAHZNIOOIVSU-UHFFFAOYSA-N [3-(1-hydroxyethyl)phenyl] methanesulfonate Chemical compound CC(O)C1=CC=CC(OS(C)(=O)=O)=C1 FRQAHZNIOOIVSU-UHFFFAOYSA-N 0.000 description 4
- 239000000010 aprotic solvent Substances 0.000 description 4
- 239000012065 filter cake Substances 0.000 description 4
- 125000005843 halogen group Chemical group 0.000 description 4
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 4
- 229940011051 isopropyl acetate Drugs 0.000 description 4
- GWYFCOCPABKNJV-UHFFFAOYSA-N isovaleric acid Chemical compound CC(C)CC(O)=O GWYFCOCPABKNJV-UHFFFAOYSA-N 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 230000009467 reduction Effects 0.000 description 4
- 238000006722 reduction reaction Methods 0.000 description 4
- COJRWHSKVYUZHQ-UHFFFAOYSA-N 3-(1-hydroxyethyl)phenol Chemical compound CC(O)C1=CC=CC(O)=C1 COJRWHSKVYUZHQ-UHFFFAOYSA-N 0.000 description 3
- COJRWHSKVYUZHQ-LURJTMIESA-N 3-[(1s)-1-hydroxyethyl]phenol Chemical compound C[C@H](O)C1=CC=CC(O)=C1 COJRWHSKVYUZHQ-LURJTMIESA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- WAPZHQZXWPVDMP-UHFFFAOYSA-N [3-(1-methylsulfonyloxyethyl)phenyl] methanesulfonate Chemical compound CS(=O)(=O)OC(C)C1=CC=CC(OS(C)(=O)=O)=C1 WAPZHQZXWPVDMP-UHFFFAOYSA-N 0.000 description 3
- QMPSUPWBJMOGPS-UHFFFAOYSA-N [Ru].CC(C)C1=CC=C(C)C=C1 Chemical compound [Ru].CC(C)C1=CC=C(C)C=C1 QMPSUPWBJMOGPS-UHFFFAOYSA-N 0.000 description 3
- 150000001298 alcohols Chemical class 0.000 description 3
- 239000012670 alkaline solution Substances 0.000 description 3
- 230000002051 biphasic effect Effects 0.000 description 3
- 238000001212 derivatisation Methods 0.000 description 3
- 125000005265 dialkylamine group Chemical group 0.000 description 3
- CCIVGXIOQKPBKL-UHFFFAOYSA-N ethanesulfonic acid Chemical compound CCS(O)(=O)=O CCIVGXIOQKPBKL-UHFFFAOYSA-N 0.000 description 3
- 235000019253 formic acid Nutrition 0.000 description 3
- 239000000543 intermediate Substances 0.000 description 3
- 239000012454 non-polar solvent Substances 0.000 description 3
- 239000003960 organic solvent Substances 0.000 description 3
- YBBRCQOCSYXUOC-UHFFFAOYSA-N sulfuryl dichloride Chemical class ClS(Cl)(=O)=O YBBRCQOCSYXUOC-UHFFFAOYSA-N 0.000 description 3
- 230000010512 thermal transition Effects 0.000 description 3
- 0 *C*C(*)c1ccccc1 Chemical compound *C*C(*)c1ccccc1 0.000 description 2
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 2
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- KJTLSVCANCCWHF-UHFFFAOYSA-N Ruthenium Chemical compound [Ru] KJTLSVCANCCWHF-UHFFFAOYSA-N 0.000 description 2
- 230000002776 aggregation Effects 0.000 description 2
- 238000013019 agitation Methods 0.000 description 2
- NHCGQXPQGHFCPN-UHFFFAOYSA-N amino methanesulfonate Chemical compound CS(=O)(=O)ON NHCGQXPQGHFCPN-UHFFFAOYSA-N 0.000 description 2
- 238000009876 asymmetric hydrogenation reaction Methods 0.000 description 2
- 230000008901 benefit Effects 0.000 description 2
- 230000021235 carbamoylation Effects 0.000 description 2
- 239000007795 chemical reaction product Substances 0.000 description 2
- 125000001309 chloro group Chemical group Cl* 0.000 description 2
- IJKVHSBPTUYDLN-UHFFFAOYSA-N dihydroxy(oxo)silane Chemical compound O[Si](O)=O IJKVHSBPTUYDLN-UHFFFAOYSA-N 0.000 description 2
- 230000000694 effects Effects 0.000 description 2
- 239000007789 gas Substances 0.000 description 2
- 230000020169 heat generation Effects 0.000 description 2
- 238000010438 heat treatment Methods 0.000 description 2
- 239000000852 hydrogen donor Substances 0.000 description 2
- 230000002779 inactivation Effects 0.000 description 2
- 239000007788 liquid Substances 0.000 description 2
- 238000010907 mechanical stirring Methods 0.000 description 2
- 238000003328 mesylation reaction Methods 0.000 description 2
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 2
- 229910052757 nitrogen Inorganic materials 0.000 description 2
- 239000012011 nucleophilic catalyst Substances 0.000 description 2
- 150000004812 organic fluorine compounds Chemical class 0.000 description 2
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 2
- 235000011007 phosphoric acid Nutrition 0.000 description 2
- 229950010673 rivastigmine hydrogen tartrate Drugs 0.000 description 2
- GWHQHAUAXRMMOT-MBANBULQSA-N rivastigmine tartrate Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O.CCN(C)C(=O)OC1=CC=CC([C@H](C)N(C)C)=C1 GWHQHAUAXRMMOT-MBANBULQSA-N 0.000 description 2
- 238000000926 separation method Methods 0.000 description 2
- 239000000126 substance Substances 0.000 description 2
- 125000003107 substituted aryl group Chemical group 0.000 description 2
- 239000000758 substrate Substances 0.000 description 2
- 150000003871 sulfonates Chemical class 0.000 description 2
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 description 2
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- C07C37/01—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis
- C07C37/055—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by replacing functional groups bound to a six-membered aromatic ring by hydroxy groups, e.g. by hydrolysis the substituted group being bound to oxygen, e.g. ether group
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- A61P25/00—Drugs for disorders of the nervous system
- A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
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- C07C269/00—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C269/04—Preparation of derivatives of carbamic acid, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups from amines with formation of carbamate groups
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- C07C213/02—Preparation of compounds containing amino and hydroxy, amino and etherified hydroxy or amino and esterified hydroxy groups bound to the same carbon skeleton by reactions involving the formation of amino groups from compounds containing hydroxy groups or etherified or esterified hydroxy groups
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- C—CHEMISTRY; METALLURGY
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- 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
- C07C303/26—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids
- C07C303/28—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids by reaction of hydroxy compounds with sulfonic acids or derivatives thereof
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- C—CHEMISTRY; METALLURGY
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- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
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- C07C303/26—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids
- C07C303/30—Preparation of esters or amides of sulfuric acids; Preparation of sulfonic acids or of their esters, halides, anhydrides or amides of esters of sulfonic acids by reactions not involving the formation of esterified sulfo groups
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C309/00—Sulfonic acids; Halides, esters, or anhydrides thereof
- C07C309/63—Esters of sulfonic acids
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
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- C07C37/001—Preparation of compounds having hydroxy or O-metal groups bound to a carbon atom of a six-membered aromatic ring by modification in a side chain
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- C07C39/02—Compounds having at least one hydroxy or O-metal group bound to a carbon atom of a six-membered aromatic ring monocyclic with no unsaturation outside the aromatic ring
- C07C39/11—Alkylated hydroxy benzenes containing also acyclically bound hydroxy groups, e.g. saligenol
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- C—CHEMISTRY; METALLURGY
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| CN105246873A (zh) * | 2013-06-14 | 2016-01-13 | 日产化学工业株式会社 | 光学活性醇化合物的制造方法 |
| CN103980270A (zh) * | 2014-05-19 | 2014-08-13 | 埃斯特维华义制药有限公司 | 一种(r)-3-奎宁醇的制备方法 |
| CN108752322A (zh) * | 2018-09-12 | 2018-11-06 | 广州新民培林医药科技有限公司 | 一种新型Tepotinib衍生物和制备方法及其在抗肿瘤药物中的应用 |
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|---|---|---|---|---|
| HU201906B (en) * | 1987-03-04 | 1991-01-28 | Sandoz Ag | Process for producing phenyl-carbamate derivative and acid additional salts and pharmaceutical compositions containing them |
| US4996235A (en) * | 1987-11-25 | 1991-02-26 | Eli Lilly And Company | 3,4-diphenylbutanamines |
| JPH0899940A (ja) * | 1994-09-30 | 1996-04-16 | Kanegafuchi Chem Ind Co Ltd | 光学活性な1−(3,4−ジメトキシフェニル)−2−アミノプロパンの製造法 |
| GB9706321D0 (en) | 1997-03-26 | 1997-05-14 | Zeneca Ltd | Catalytic hydrogenation |
| JP3938651B2 (ja) * | 2000-04-13 | 2007-06-27 | セントラル硝子株式会社 | 光学活性α−メチル−ビス−3、5−(トリフルオロメチル)ベンジルアミンの製造方法 |
| KR20030062447A (ko) | 2000-12-25 | 2003-07-25 | 아지노모토 가부시키가이샤 | 광학 활성 할로하이드린 화합물의 제조방법 |
| WO2005005355A1 (en) * | 2003-07-08 | 2005-01-20 | Unilever Plc | Process for the preparation of a cosmetic active |
| GB0329284D0 (en) | 2003-12-18 | 2004-01-21 | Avecia Ltd | Process |
| KR101085804B1 (ko) | 2004-03-29 | 2011-11-22 | 간토 가가꾸 가부시키가이샤 | 광학 활성 알코올의 제법 |
| US6939981B1 (en) * | 2004-06-25 | 2005-09-06 | Eastman Chemical Company | Ruthenium complexes of phosphine-aminophosphine ligands |
| EP1856036B1 (en) * | 2004-11-08 | 2016-12-14 | Emcure Pharmaceuticals Limited | An efficient method for preparation of (s)-3-[(1-dimethyl amino)ethyl]-phenyl-n-ethyl-n-methyl-carbamate |
| WO2006137167A1 (ja) * | 2005-06-20 | 2006-12-28 | Kanto Kagaku Kabushiki Kaisha | スルホナート触媒及びそれを利用したアルコール化合物の製法 |
| TWI389709B (zh) | 2005-12-01 | 2013-03-21 | Novartis Ag | 經皮治療系統 |
| WO2007147897A1 (de) | 2006-06-23 | 2007-12-27 | Basf Se | Verfahren zur herstellung von optisch aktiven 2-halogen-1-phenylethanol-derivaten und folgeprodukten davon |
| WO2009132443A1 (en) | 2008-05-01 | 2009-11-05 | Kanata Chemical Technologies Inc. | Cationic transition-metal arene catalysts |
-
2008
- 2008-12-24 GB GBGB0823554.1A patent/GB0823554D0/en not_active Ceased
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2009
- 2009-12-17 US US12/653,748 patent/US8415508B2/en not_active Expired - Fee Related
- 2009-12-22 AR ARP090105061A patent/AR075496A1/es not_active Application Discontinuation
- 2009-12-23 SG SG2011042108A patent/SG172052A1/en unknown
- 2009-12-23 JP JP2011542822A patent/JP2012513966A/ja active Pending
- 2009-12-23 KR KR1020117017258A patent/KR20110098964A/ko not_active Ceased
- 2009-12-23 NZ NZ593493A patent/NZ593493A/xx not_active IP Right Cessation
- 2009-12-23 WO PCT/EP2009/067821 patent/WO2010072798A1/en not_active Ceased
- 2009-12-23 TW TW098144595A patent/TW201035028A/zh unknown
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- 2009-12-23 CA CA2748349A patent/CA2748349A1/en not_active Abandoned
- 2009-12-23 MA MA34036A patent/MA32983B1/fr unknown
- 2009-12-23 CN CN2009801523437A patent/CN102264672A/zh active Pending
- 2009-12-23 BR BRPI0923394A patent/BRPI0923394A2/pt not_active IP Right Cessation
- 2009-12-23 EP EP09799106A patent/EP2382172A1/en not_active Withdrawn
- 2009-12-23 MY MYPI20112891 patent/MY151103A/en unknown
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- 2011-06-13 IL IL213520A patent/IL213520A0/en unknown
- 2011-06-23 CL CL2011001563A patent/CL2011001563A1/es unknown
- 2011-06-29 CO CO11081447A patent/CO6382153A2/es active IP Right Grant
- 2011-07-22 EC EC2011011221A patent/ECSP11011221A/es unknown
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Also Published As
| Publication number | Publication date |
|---|---|
| NZ593493A (en) | 2013-03-28 |
| AR075496A1 (es) | 2011-04-06 |
| MY151103A (en) | 2014-04-15 |
| MA32983B1 (fr) | 2012-01-02 |
| MX2011006918A (es) | 2011-07-29 |
| CN102264672A (zh) | 2011-11-30 |
| AU2009331493A1 (en) | 2011-07-07 |
| US8637713B2 (en) | 2014-01-28 |
| US8415508B2 (en) | 2013-04-09 |
| JP2012513966A (ja) | 2012-06-21 |
| TW201035028A (en) | 2010-10-01 |
| AU2009331493B2 (en) | 2013-03-07 |
| ECSP11011221A (es) | 2011-08-31 |
| IL213520A0 (en) | 2011-07-31 |
| US20100168229A1 (en) | 2010-07-01 |
| SG172052A1 (en) | 2011-07-28 |
| CL2011001563A1 (es) | 2012-01-13 |
| US20130096337A1 (en) | 2013-04-18 |
| CA2748349A1 (en) | 2010-07-01 |
| GB0823554D0 (en) | 2009-01-28 |
| EP2382172A1 (en) | 2011-11-02 |
| WO2010072798A1 (en) | 2010-07-01 |
| CO6382153A2 (es) | 2012-02-15 |
| BRPI0923394A2 (pt) | 2016-01-12 |
| TN2011000290A1 (en) | 2012-12-17 |
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