JP2000507970A - キラルメディエータの効率的な合成 - Google Patents
キラルメディエータの効率的な合成Info
- Publication number
- JP2000507970A JP2000507970A JP10531222A JP53122298A JP2000507970A JP 2000507970 A JP2000507970 A JP 2000507970A JP 10531222 A JP10531222 A JP 10531222A JP 53122298 A JP53122298 A JP 53122298A JP 2000507970 A JP2000507970 A JP 2000507970A
- Authority
- JP
- Japan
- Prior art keywords
- compound
- formula
- phenyl
- solution
- toluene
- 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.)
- Pending
Links
- 230000015572 biosynthetic process Effects 0.000 title abstract description 14
- 238000003786 synthesis reaction Methods 0.000 title abstract description 12
- 238000000034 method Methods 0.000 claims abstract description 138
- 150000001875 compounds Chemical class 0.000 claims abstract description 93
- 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 claims abstract description 5
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Natural products CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 212
- 239000000243 solution Substances 0.000 claims description 78
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 57
- 239000002904 solvent Substances 0.000 claims description 50
- 238000006243 chemical reaction Methods 0.000 claims description 47
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 43
- -1 Phenyl Chemical group 0.000 claims description 40
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 35
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 27
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 27
- ULTHEAFYOOPTTB-UHFFFAOYSA-N 1,4-dibromobutane Chemical compound BrCCCCBr ULTHEAFYOOPTTB-UHFFFAOYSA-N 0.000 claims description 24
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 24
- 239000002002 slurry Substances 0.000 claims description 24
- RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Substances C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 claims description 24
- 150000003839 salts Chemical class 0.000 claims description 22
- 239000002253 acid Substances 0.000 claims description 20
- 239000010410 layer Substances 0.000 claims description 20
- WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 claims description 18
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 18
- 125000000217 alkyl group Chemical group 0.000 claims description 18
- 125000005842 heteroatom Chemical group 0.000 claims description 18
- 229910052760 oxygen Inorganic materials 0.000 claims description 18
- 229920006395 saturated elastomer Polymers 0.000 claims description 18
- UZFMOKQJFYMBGY-UHFFFAOYSA-N 4-hydroxy-TEMPO Chemical compound CC1(C)CC(O)CC(C)(C)N1[O] UZFMOKQJFYMBGY-UHFFFAOYSA-N 0.000 claims description 17
- 239000007864 aqueous solution Substances 0.000 claims description 17
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 15
- DLNKOYKMWOXYQA-UHFFFAOYSA-N dl-pseudophenylpropanolamine Natural products CC(N)C(O)C1=CC=CC=C1 DLNKOYKMWOXYQA-UHFFFAOYSA-N 0.000 claims description 15
- 230000035484 reaction time Effects 0.000 claims description 15
- 238000010992 reflux Methods 0.000 claims description 15
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 claims description 15
- DLNKOYKMWOXYQA-CBAPKCEASA-N (-)-norephedrine Chemical compound C[C@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-CBAPKCEASA-N 0.000 claims description 14
- 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 claims description 14
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 14
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 14
- 239000011734 sodium Substances 0.000 claims description 14
- 239000012044 organic layer Substances 0.000 claims description 13
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 12
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 12
- 125000003944 tolyl group Chemical group 0.000 claims description 12
- 239000011260 aqueous acid Substances 0.000 claims description 11
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 claims description 11
- 229910000041 hydrogen chloride Inorganic materials 0.000 claims description 11
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 11
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 claims description 10
- 239000007787 solid Substances 0.000 claims description 10
- 125000003545 alkoxy group Chemical group 0.000 claims description 9
- 239000002168 alkylating agent Substances 0.000 claims description 9
- 229940100198 alkylating agent Drugs 0.000 claims description 9
- 230000002051 biphasic effect Effects 0.000 claims description 9
- 238000001914 filtration Methods 0.000 claims description 9
- 238000004519 manufacturing process Methods 0.000 claims description 9
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 claims description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 claims description 8
- WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 claims description 8
- 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 8
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 8
- 150000007522 mineralic acids Chemical class 0.000 claims description 8
- 150000007524 organic acids Chemical class 0.000 claims description 8
- 238000005406 washing Methods 0.000 claims description 8
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 7
- 238000002156 mixing Methods 0.000 claims description 7
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 7
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 7
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 claims description 6
- 150000001218 Thorium Chemical class 0.000 claims description 6
- XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 claims description 6
- DZGCGKFAPXFTNM-UHFFFAOYSA-N ethanol;hydron;chloride Chemical compound Cl.CCO DZGCGKFAPXFTNM-UHFFFAOYSA-N 0.000 claims description 6
- 238000010533 azeotropic distillation Methods 0.000 claims description 5
- GYNNXHKOJHMOHS-UHFFFAOYSA-N methyl-cycloheptane Natural products CC1CCCCCC1 GYNNXHKOJHMOHS-UHFFFAOYSA-N 0.000 claims description 5
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 5
- 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 4
- 239000005711 Benzoic acid Substances 0.000 claims description 4
- CPELXLSAUQHCOX-UHFFFAOYSA-N Hydrogen bromide Chemical compound Br CPELXLSAUQHCOX-UHFFFAOYSA-N 0.000 claims description 4
- 235000010233 benzoic acid Nutrition 0.000 claims description 4
- 235000019253 formic acid Nutrition 0.000 claims description 4
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims description 3
- 239000004202 carbamide Substances 0.000 claims description 3
- 239000007789 gas Substances 0.000 claims description 3
- VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 3
- 239000011976 maleic acid Substances 0.000 claims description 3
- 238000006386 neutralization reaction Methods 0.000 claims description 3
- 230000003472 neutralizing effect Effects 0.000 claims description 3
- FZJCXIDLUFPGPP-UHFFFAOYSA-N propan-2-ol;toluene Chemical compound CC(C)O.CC1=CC=CC=C1 FZJCXIDLUFPGPP-UHFFFAOYSA-N 0.000 claims description 3
- 239000000126 substance Substances 0.000 claims description 3
- VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 3
- OPFJDXRVMFKJJO-ZHHKINOHSA-N N-{[3-(2-benzamido-4-methyl-1,3-thiazol-5-yl)-pyrazol-5-yl]carbonyl}-G-dR-G-dD-dD-dD-NH2 Chemical compound S1C(C=2NN=C(C=2)C(=O)NCC(=O)N[C@H](CCCN=C(N)N)C(=O)NCC(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC(O)=O)C(N)=O)=C(C)N=C1NC(=O)C1=CC=CC=C1 OPFJDXRVMFKJJO-ZHHKINOHSA-N 0.000 claims description 2
- 150000001414 amino alcohols Chemical class 0.000 claims description 2
- 229940126086 compound 21 Drugs 0.000 claims description 2
- 230000001568 sexual effect Effects 0.000 claims description 2
- 238000002360 preparation method Methods 0.000 abstract description 9
- 238000002955 isolation Methods 0.000 abstract description 4
- 239000002585 base Substances 0.000 description 30
- 239000000047 product Substances 0.000 description 19
- 238000004128 high performance liquid chromatography Methods 0.000 description 17
- 150000003840 hydrochlorides Chemical class 0.000 description 7
- 229960000395 phenylpropanolamine Drugs 0.000 description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
- 238000007259 addition reaction Methods 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 239000011541 reaction mixture Substances 0.000 description 6
- 238000007792 addition Methods 0.000 description 5
- XBRDBODLCHKXHI-UHFFFAOYSA-N epolamine Chemical compound OCCN1CCCC1 XBRDBODLCHKXHI-UHFFFAOYSA-N 0.000 description 5
- 239000000706 filtrate Substances 0.000 description 5
- DLNKOYKMWOXYQA-APPZFPTMSA-N phenylpropanolamine Chemical compound C[C@@H](N)[C@H](O)C1=CC=CC=C1 DLNKOYKMWOXYQA-APPZFPTMSA-N 0.000 description 5
- 125000002827 triflate group Chemical group FC(S(=O)(=O)O*)(F)F 0.000 description 5
- UFWIBTONFRDIAS-UHFFFAOYSA-N Naphthalene Chemical compound C1=CC=CC2=CC=CC=C21 UFWIBTONFRDIAS-UHFFFAOYSA-N 0.000 description 4
- XPOQHMRABVBWPR-ZDUSSCGKSA-N efavirenz Chemical compound C([C@]1(C2=CC(Cl)=CC=C2NC(=O)O1)C(F)(F)F)#CC1CC1 XPOQHMRABVBWPR-ZDUSSCGKSA-N 0.000 description 4
- 229910052757 nitrogen Inorganic materials 0.000 description 4
- 239000013078 crystal Substances 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000012458 free base Substances 0.000 description 3
- 239000011521 glass Substances 0.000 description 3
- 238000002347 injection Methods 0.000 description 3
- 239000007924 injection Substances 0.000 description 3
- 229910017053 inorganic salt Inorganic materials 0.000 description 3
- 239000007788 liquid Substances 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000008363 phosphate buffer Substances 0.000 description 3
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 238000003756 stirring Methods 0.000 description 3
- CMQCNTNASCDNGR-UHFFFAOYSA-N toluene;hydrate Chemical compound O.CC1=CC=CC=C1 CMQCNTNASCDNGR-UHFFFAOYSA-N 0.000 description 3
- ULSIYEODSMZIPX-QMMMGPOBSA-N (1r)-2-amino-1-phenylethanol Chemical compound NC[C@H](O)C1=CC=CC=C1 ULSIYEODSMZIPX-QMMMGPOBSA-N 0.000 description 2
- HRWCWYGWEVVDLT-DTWKUNHWSA-N (1r,2s)-2-amino-2,3-dihydro-1h-inden-1-ol Chemical compound C1=CC=C2[C@@H](O)[C@@H](N)CC2=C1 HRWCWYGWEVVDLT-DTWKUNHWSA-N 0.000 description 2
- VEFLKXRACNJHOV-UHFFFAOYSA-N 1,3-dibromopropane Chemical compound BrCCCBr VEFLKXRACNJHOV-UHFFFAOYSA-N 0.000 description 2
- IBODDUNKEPPBKW-UHFFFAOYSA-N 1,5-dibromopentane Chemical compound BrCCCCCBr IBODDUNKEPPBKW-UHFFFAOYSA-N 0.000 description 2
- 239000003795 chemical substances by application Substances 0.000 description 2
- 239000005457 ice water Substances 0.000 description 2
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 2
- NLRKCXQQSUWLCH-UHFFFAOYSA-N nitrosobenzene Chemical compound O=NC1=CC=CC=C1 NLRKCXQQSUWLCH-UHFFFAOYSA-N 0.000 description 2
- 239000004810 polytetrafluoroethylene Substances 0.000 description 2
- 229920001343 polytetrafluoroethylene Polymers 0.000 description 2
- 239000006228 supernatant Substances 0.000 description 2
- LOPKSXMQWBYUOI-BDAKNGLRSA-N (1s,2r)-1-amino-2,3-dihydro-1h-inden-2-ol Chemical compound C1=CC=C2[C@H](N)[C@H](O)CC2=C1 LOPKSXMQWBYUOI-BDAKNGLRSA-N 0.000 description 1
- WDDUDOBVGMCQRF-UWVGGRQHSA-N (1s,2s)-2-amino-2-methoxy-1-phenylpropan-1-ol Chemical compound CO[C@](C)(N)[C@@H](O)C1=CC=CC=C1 WDDUDOBVGMCQRF-UWVGGRQHSA-N 0.000 description 1
- IJXJGQCXFSSHNL-QMMMGPOBSA-N (R)-(-)-2-Phenylglycinol Chemical compound OC[C@H](N)C1=CC=CC=C1 IJXJGQCXFSSHNL-QMMMGPOBSA-N 0.000 description 1
- KGKAYWMGPDWLQZ-UHFFFAOYSA-N 1,2-bis(bromomethyl)benzene Chemical group BrCC1=CC=CC=C1CBr KGKAYWMGPDWLQZ-UHFFFAOYSA-N 0.000 description 1
- GCZOMCDXYFMAGP-UHFFFAOYSA-N 1,8-bis(bromomethyl)naphthalene Chemical compound C1=CC(CBr)=C2C(CBr)=CC=CC2=C1 GCZOMCDXYFMAGP-UHFFFAOYSA-N 0.000 description 1
- FWYHRXVCIWHPMO-UHFFFAOYSA-N 1-(2-bromoethyl)-2-(bromomethyl)benzene Chemical compound BrCCC1=CC=CC=C1CBr FWYHRXVCIWHPMO-UHFFFAOYSA-N 0.000 description 1
- MLRVZFYXUZQSRU-UHFFFAOYSA-N 1-chlorohexane Chemical compound CCCCCCCl MLRVZFYXUZQSRU-UHFFFAOYSA-N 0.000 description 1
- HSFRODBENVJLHS-UHFFFAOYSA-N 2,3-bis(bromomethyl)naphthalene Chemical compound C1=CC=C2C=C(CBr)C(CBr)=CC2=C1 HSFRODBENVJLHS-UHFFFAOYSA-N 0.000 description 1
- QUHLMDHKWFNZOT-UHFFFAOYSA-N 2,3-bis(bromomethyl)pyridine Chemical compound BrCC1=CC=CN=C1CBr QUHLMDHKWFNZOT-UHFFFAOYSA-N 0.000 description 1
- UBBFEIFODYNEKU-UHFFFAOYSA-N 2-(2-bromoethyl)-3-(bromomethyl)pyridine Chemical compound BrCCC1=NC=CC=C1CBr UBBFEIFODYNEKU-UHFFFAOYSA-N 0.000 description 1
- 125000005999 2-bromoethyl group Chemical group 0.000 description 1
- UPHZRNLSTVRKNN-UHFFFAOYSA-N 3-(2-bromoethyl)-4-(bromomethyl)pyridine Chemical compound BrCCC1=CN=CC=C1CBr UPHZRNLSTVRKNN-UHFFFAOYSA-N 0.000 description 1
- ACTCQLFWYOCRKF-UHFFFAOYSA-N 4-(2-bromoethyl)-3-(bromomethyl)pyridine Chemical compound BrCCC1=CC=NC=C1CBr ACTCQLFWYOCRKF-UHFFFAOYSA-N 0.000 description 1
- HQQTZCPKNZVLFF-UHFFFAOYSA-N 4h-1,2-benzoxazin-3-one Chemical class C1=CC=C2ONC(=O)CC2=C1 HQQTZCPKNZVLFF-UHFFFAOYSA-N 0.000 description 1
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 1
- ZGUNAGUHMKGQNY-SSDOTTSWSA-N D-alpha-phenylglycine Chemical compound OC(=O)[C@H](N)C1=CC=CC=C1 ZGUNAGUHMKGQNY-SSDOTTSWSA-N 0.000 description 1
- 102100034343 Integrase Human genes 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- 241000282376 Panthera tigris Species 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 108010092799 RNA-directed DNA polymerase Proteins 0.000 description 1
- 150000001299 aldehydes Chemical class 0.000 description 1
- 230000029936 alkylation Effects 0.000 description 1
- 238000005804 alkylation reaction Methods 0.000 description 1
- 150000001413 amino acids Chemical class 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- AGEZXYOZHKGVCM-UHFFFAOYSA-N benzyl bromide Chemical compound BrCC1=CC=CC=C1 AGEZXYOZHKGVCM-UHFFFAOYSA-N 0.000 description 1
- 125000005997 bromomethyl group Chemical group 0.000 description 1
- 229910052799 carbon Inorganic materials 0.000 description 1
- CZTQZXZIADLWOZ-CRAIPNDOSA-N cefaloridine Chemical compound O=C([C@@H](NC(=O)CC=1SC=CC=1)[C@H]1SC2)N1C(C(=O)[O-])=C2C[N+]1=CC=CC=C1 CZTQZXZIADLWOZ-CRAIPNDOSA-N 0.000 description 1
- 239000003610 charcoal Substances 0.000 description 1
- 150000001805 chlorine compounds Chemical class 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 239000008367 deionised water Substances 0.000 description 1
- 229910021641 deionized water Inorganic materials 0.000 description 1
- VWWMOACCGFHMEV-UHFFFAOYSA-N dicarbide(2-) Chemical compound [C-]#[C-] VWWMOACCGFHMEV-UHFFFAOYSA-N 0.000 description 1
- 238000004090 dissolution Methods 0.000 description 1
- 238000004821 distillation Methods 0.000 description 1
- KVJUYUKNCVBWOX-UHFFFAOYSA-N ethanol;pyrrolidine Chemical compound CCO.C1CCNC1 KVJUYUKNCVBWOX-UHFFFAOYSA-N 0.000 description 1
- MJDDHOXHJDDWBP-UHFFFAOYSA-N ethynylcyclopropane Chemical compound [C-]#CC1CC1 MJDDHOXHJDDWBP-UHFFFAOYSA-N 0.000 description 1
- 238000004817 gas chromatography Methods 0.000 description 1
- 238000010438 heat treatment Methods 0.000 description 1
- 125000000623 heterocyclic group Chemical group 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000012535 impurity Substances 0.000 description 1
- 238000011065 in-situ storage Methods 0.000 description 1
- 230000006698 induction Effects 0.000 description 1
- 230000002452 interceptive effect Effects 0.000 description 1
- 150000004694 iodide salts Chemical class 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 229940098779 methanesulfonic acid Drugs 0.000 description 1
- IJDNQMDRQITEOD-UHFFFAOYSA-N n-butane Chemical compound CCCC IJDNQMDRQITEOD-UHFFFAOYSA-N 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 239000012429 reaction media Substances 0.000 description 1
- 238000011084 recovery Methods 0.000 description 1
- 238000007363 ring formation reaction Methods 0.000 description 1
- 238000000926 separation method Methods 0.000 description 1
- 238000010512 small scale reaction Methods 0.000 description 1
- 150000003613 toluenes Chemical class 0.000 description 1
- ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 1
- 150000008648 triflates Chemical class 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D221/00—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00
- C07D221/02—Heterocyclic compounds containing six-membered rings having one nitrogen atom as the only ring hetero atom, not provided for by groups C07D211/00 - C07D219/00 condensed with carbocyclic rings or ring systems
- C07D221/04—Ortho- or peri-condensed ring systems
- C07D221/06—Ring systems of three rings
- C07D221/14—Aza-phenalenes, e.g. 1,8-naphthalimide
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D205/00—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom
- C07D205/02—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings
- C07D205/04—Heterocyclic compounds containing four-membered rings with one nitrogen atom as the only ring hetero atom not condensed with other rings having no double bonds between ring members or between ring members and non-ring members
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D209/00—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom
- C07D209/02—Heterocyclic compounds containing five-membered rings, condensed with other rings, with one nitrogen atom as the only ring hetero atom condensed with one carbocyclic ring
- C07D209/44—Iso-indoles; Hydrogenated iso-indoles
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/084—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings
- C07D295/092—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms attached to the same carbon chain, which is not interrupted by carbocyclic rings with aromatic radicals attached to the chain
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D295/00—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms
- C07D295/04—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms
- C07D295/08—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms
- C07D295/096—Heterocyclic compounds containing polymethylene-imine rings with at least five ring members, 3-azabicyclo [3.2.2] nonane, piperazine, morpholine or thiomorpholine rings, having only hydrogen atoms directly attached to the ring carbon atoms with substituted hydrocarbon radicals attached to ring nitrogen atoms substituted by singly bound oxygen or sulfur atoms with the ring nitrogen atoms and the oxygen or sulfur atoms separated by carbocyclic rings or by carbon chains interrupted by carbocyclic rings
-
- 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
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C2602/00—Systems containing two condensed rings
- C07C2602/02—Systems containing two condensed rings the rings having only two atoms in common
- C07C2602/04—One of the condensed rings being a six-membered aromatic ring
- C07C2602/08—One of the condensed rings being a six-membered aromatic ring the other ring being five-membered, e.g. indane
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Lasers (AREA)
- Indole Compounds (AREA)
Applications Claiming Priority (11)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US3492697P | 1997-01-10 | 1997-01-10 | |
| GBGB9704194.1A GB9704194D0 (en) | 1997-02-28 | 1997-02-28 | Efficient synthesis of a chiral mediator |
| GB9704194.1 | 1997-02-28 | ||
| US4202197P | 1997-04-17 | 1997-04-17 | |
| US4516797P | 1997-04-30 | 1997-04-30 | |
| GB9710393.1 | 1997-05-20 | ||
| GBGB9710393.1A GB9710393D0 (en) | 1997-05-20 | 1997-05-20 | Efficient synthesis of a chiral mediator |
| GB60/045,167 | 1997-05-20 | ||
| GB60/034,926 | 1997-05-20 | ||
| GB60/042,021 | 1997-05-20 | ||
| PCT/US1998/000578 WO1998030540A1 (en) | 1997-01-10 | 1998-01-06 | Efficient synthesis of a chiral mediator |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JP2000507970A true JP2000507970A (ja) | 2000-06-27 |
Family
ID=27517397
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP10531222A Pending JP2000507970A (ja) | 1997-01-10 | 1998-01-06 | キラルメディエータの効率的な合成 |
Country Status (5)
| Country | Link |
|---|---|
| EP (1) | EP0973737A4 (de) |
| JP (1) | JP2000507970A (de) |
| AU (1) | AU732430B2 (de) |
| CA (1) | CA2276074A1 (de) |
| WO (1) | WO1998030540A1 (de) |
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003531197A (ja) * | 2000-04-20 | 2003-10-21 | デグサ アクチエンゲゼルシャフト | ２，５−ジケトピペラジンの製造方法、２，５−ジケトピペラジン、ジペプチド及びその使用 |
Families Citing this family (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| AR011731A1 (es) * | 1997-05-16 | 2000-08-30 | Merck & Co Inc | Un proceso de reaccion de adicion enantioselectiva eficiente utilizando un reactivo de organozinc. |
| WO2010115638A2 (en) | 2009-04-09 | 2010-10-14 | Lonza Ltd. | Autocatalytic process for the synthesis of chiral propargylic alcohols |
| WO2010115639A1 (en) | 2009-04-09 | 2010-10-14 | Lonza Ltd | Process for the synthesis of a propargylic alcohol |
| EP2447247A1 (de) | 2010-10-14 | 2012-05-02 | Lonza Ltd. | Prozess zur Synthese von chiralen Propargylalkoholen |
| EP2447255A1 (de) | 2010-10-14 | 2012-05-02 | Lonza Ltd. | Verfahren zur Synthese von zyklischen Carbamaten |
Family Cites Families (9)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US3028378A (en) * | 1962-04-03 | Pharmacologically active compounds | ||
| BE481067A (de) * | 1947-05-23 | |||
| US2552502A (en) * | 1947-09-11 | 1951-05-08 | Upjohn Co | Beta-(pyrrolidyl-1)-propanol-2 |
| US2723269A (en) * | 1949-11-03 | 1955-11-08 | American Cyanamid Co | Piperidino tertiary amino alcohols |
| US2975193A (en) * | 1959-06-18 | 1961-03-14 | Parke Davis & Co | Organic amine compounds and method of obtaining the same |
| US3468893A (en) * | 1966-03-14 | 1969-09-23 | Ciba Geigy Corp | 1-substituted-diphenyl-azacycloalkenes |
| US3754003A (en) * | 1971-07-08 | 1973-08-21 | A Pedrazzoli | Tetramethyl pyrrolidine derivatives |
| IL117440A0 (en) * | 1995-03-31 | 1996-07-23 | Pfizer | Pyrrolidinyl hydroxamic acid compounds and their production process |
| US5633405A (en) * | 1995-05-25 | 1997-05-27 | Merck & Co., Inc. | Asymmetric synthesis of (-)-6-chloro-4-cyclopropyl-ethynyl-4-trifluoromethyl-1,4-dihydro-2H-3,1-benzoxanzin-2-one |
-
1998
- 1998-01-06 EP EP98903459A patent/EP0973737A4/de not_active Withdrawn
- 1998-01-06 AU AU60225/98A patent/AU732430B2/en not_active Ceased
- 1998-01-06 WO PCT/US1998/000578 patent/WO1998030540A1/en not_active Ceased
- 1998-01-06 JP JP10531222A patent/JP2000507970A/ja active Pending
- 1998-01-06 CA CA002276074A patent/CA2276074A1/en not_active Abandoned
Cited By (1)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2003531197A (ja) * | 2000-04-20 | 2003-10-21 | デグサ アクチエンゲゼルシャフト | ２，５−ジケトピペラジンの製造方法、２，５−ジケトピペラジン、ジペプチド及びその使用 |
Also Published As
| Publication number | Publication date |
|---|---|
| WO1998030540A1 (en) | 1998-07-16 |
| CA2276074A1 (en) | 1998-07-16 |
| AU732430B2 (en) | 2001-04-26 |
| EP0973737A4 (de) | 2000-04-26 |
| EP0973737A1 (de) | 2000-01-26 |
| AU6022598A (en) | 1998-08-03 |
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