JPH0827079A - アルファ−アミノアルカン酸及還元生成物 - Google Patents
アルファ−アミノアルカン酸及還元生成物Info
- Publication number
- JPH0827079A JPH0827079A JP7092827A JP9282795A JPH0827079A JP H0827079 A JPH0827079 A JP H0827079A JP 7092827 A JP7092827 A JP 7092827A JP 9282795 A JP9282795 A JP 9282795A JP H0827079 A JPH0827079 A JP H0827079A
- Authority
- JP
- Japan
- Prior art keywords
- alkoxy
- alkyl
- lower alkoxy
- lower alkyl
- hydroxy
- 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
- 239000002253 acid Substances 0.000 title claims description 19
- -1 carboxy, formyl Chemical group 0.000 claims abstract description 407
- 150000001875 compounds Chemical class 0.000 claims abstract description 153
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 123
- 150000003839 salts Chemical class 0.000 claims abstract description 100
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 84
- 239000001257 hydrogen Substances 0.000 claims abstract description 84
- 125000001931 aliphatic group Chemical group 0.000 claims abstract description 83
- 150000002431 hydrogen Chemical class 0.000 claims abstract description 47
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 35
- 125000001072 heteroaryl group Chemical group 0.000 claims abstract description 30
- 125000003118 aryl group Chemical group 0.000 claims abstract description 22
- 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims abstract description 22
- 125000003396 thiol group Chemical group [H]S* 0.000 claims abstract description 10
- 238000004519 manufacturing process Methods 0.000 claims abstract description 8
- 125000003545 alkoxy group Chemical group 0.000 claims description 820
- 125000000217 alkyl group Chemical group 0.000 claims description 775
- 229910052757 nitrogen Inorganic materials 0.000 claims description 68
- 125000004122 cyclic group Chemical group 0.000 claims description 62
- 229910052736 halogen Inorganic materials 0.000 claims description 55
- 150000002367 halogens Chemical class 0.000 claims description 55
- 239000000203 mixture Substances 0.000 claims description 47
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 43
- 125000003282 alkyl amino group Chemical group 0.000 claims description 38
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 34
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
- 125000003302 alkenyloxy group Chemical group 0.000 claims description 30
- 125000001624 naphthyl group Chemical group 0.000 claims description 28
- 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 27
- 229910052717 sulfur Inorganic materials 0.000 claims description 25
- 125000005530 alkylenedioxy group Chemical group 0.000 claims description 24
- 125000001589 carboacyl group Chemical group 0.000 claims description 23
- 125000003342 alkenyl group Chemical group 0.000 claims description 21
- 238000007796 conventional method Methods 0.000 claims description 21
- 125000002947 alkylene group Chemical group 0.000 claims description 19
- 239000000126 substance Substances 0.000 claims description 19
- 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 17
- 125000005605 benzo group Chemical group 0.000 claims description 16
- 230000004927 fusion Effects 0.000 claims description 16
- 238000000034 method Methods 0.000 claims description 15
- PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 13
- 229910052751 metal Inorganic materials 0.000 claims description 12
- 239000002184 metal Substances 0.000 claims description 12
- 125000004423 acyloxy group Chemical group 0.000 claims description 11
- 125000004414 alkyl thio group Chemical group 0.000 claims description 11
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 11
- 125000006239 protecting group Chemical group 0.000 claims description 11
- 125000004076 pyridyl group Chemical group 0.000 claims description 10
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
- 125000002112 pyrrolidino group Chemical group [*]N1C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 8
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 7
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 7
- 229910052794 bromium Inorganic materials 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 7
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 claims description 7
- 238000002360 preparation method Methods 0.000 claims description 7
- 150000001204 N-oxides Chemical class 0.000 claims description 6
- 125000005236 alkanoylamino group Chemical group 0.000 claims description 6
- XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 5
- 125000005194 alkoxycarbonyloxy group Chemical group 0.000 claims description 5
- 125000005115 alkyl carbamoyl group Chemical group 0.000 claims description 5
- 150000001412 amines Chemical class 0.000 claims description 5
- 125000003277 amino group Chemical group 0.000 claims description 5
- 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 5
- 125000000714 pyrimidinyl group Chemical group 0.000 claims description 5
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 claims description 4
- 150000001299 aldehydes Chemical class 0.000 claims description 4
- 125000005092 alkenyloxycarbonyl group Chemical group 0.000 claims description 4
- 125000005103 alkyl silyl group Chemical group 0.000 claims description 4
- 150000002148 esters Chemical class 0.000 claims description 4
- 125000001475 halogen functional group Chemical group 0.000 claims description 4
- 125000001041 indolyl group Chemical group 0.000 claims description 4
- 239000011777 magnesium Substances 0.000 claims description 4
- 229910052749 magnesium Inorganic materials 0.000 claims description 4
- 125000005030 pyridylthio group Chemical group N1=C(C=CC=C1)S* 0.000 claims description 4
- 125000004469 siloxy group Chemical group [SiH3]O* 0.000 claims description 4
- 125000001544 thienyl group Chemical group 0.000 claims description 4
- 238000009833 condensation Methods 0.000 claims description 3
- 230000005494 condensation Effects 0.000 claims description 3
- 125000005493 quinolyl group Chemical group 0.000 claims description 3
- CZWSZZHGSNZRMW-UHFFFAOYSA-N 1,2-dibromobutane Chemical compound CCC(Br)CBr CZWSZZHGSNZRMW-UHFFFAOYSA-N 0.000 claims description 2
- VYULUPAUGRISIC-IDISGSTGSA-N C(C)(C)(C)OC(=O)[C@@](C=O)(C[C@@H](C(C)C)CC1=CC(=C(C=C1)C(C)(C)C)OCCCOC)N Chemical compound C(C)(C)(C)OC(=O)[C@@](C=O)(C[C@@H](C(C)C)CC1=CC(=C(C=C1)C(C)(C)C)OCCCOC)N VYULUPAUGRISIC-IDISGSTGSA-N 0.000 claims description 2
- XXXBIRCHTUTBBN-OFVILXPXSA-N C(C)(C)(C)OC(=O)[C@@](C=O)(C[C@@H](C(C)C)CC1=CC(=C(C=C1)CC)OCCCOC)N Chemical compound C(C)(C)(C)OC(=O)[C@@](C=O)(C[C@@H](C(C)C)CC1=CC(=C(C=C1)CC)OCCCOC)N XXXBIRCHTUTBBN-OFVILXPXSA-N 0.000 claims description 2
- WOFZTTFPAFLAFH-QCDSWUKFSA-N C(C)(C)(C)OC(=O)[C@@](C=O)(C[C@@H](C(C)C)CC1=CC(=C(C=C1)OCC1=CC=CC=C1)OCCCOC)N Chemical compound C(C)(C)(C)OC(=O)[C@@](C=O)(C[C@@H](C(C)C)CC1=CC(=C(C=C1)OCC1=CC=CC=C1)OCCCOC)N WOFZTTFPAFLAFH-QCDSWUKFSA-N 0.000 claims description 2
- ZEJFNPBFFRVFPF-DWACAAAGSA-N C(C)(C)(C)OC(=O)[C@@](C=O)(C[C@@H](C(C)C)CC1=CC(=C2C(=C1)OCCO2)OCC1=CC=CC=C1)N Chemical compound C(C)(C)(C)OC(=O)[C@@](C=O)(C[C@@H](C(C)C)CC1=CC(=C2C(=C1)OCCO2)OCC1=CC=CC=C1)N ZEJFNPBFFRVFPF-DWACAAAGSA-N 0.000 claims description 2
- AOSKITADUVWYLQ-ZHRRBRCNSA-N C(C)(C)(C)OC(=O)[C@@](C=O)(C[C@H](CC)CC1=CC=C(C=C1)C(C)(C)C)N Chemical compound C(C)(C)(C)OC(=O)[C@@](C=O)(C[C@H](CC)CC1=CC=C(C=C1)C(C)(C)C)N AOSKITADUVWYLQ-ZHRRBRCNSA-N 0.000 claims description 2
- JZNQKKINOOEFCL-CYFREDJKSA-N C(C)OC([C@](C[C@@H](C(C)C)C1=CC=C(C=C1)C(C)(C)C)(N)C(=O)OC(C)(C)C)=O Chemical compound C(C)OC([C@](C[C@@H](C(C)C)C1=CC=C(C=C1)C(C)(C)C)(N)C(=O)OC(C)(C)C)=O JZNQKKINOOEFCL-CYFREDJKSA-N 0.000 claims description 2
- DWFCQTJLYQKITB-CUNXSJBXSA-N C(C)OC([C@](C[C@@H](C(C)C)CC1=CC(=C(C=C1)CC)OCCCOC)(N)C(=O)OC(C)(C)C)=O Chemical compound C(C)OC([C@](C[C@@H](C(C)C)CC1=CC(=C(C=C1)CC)OCCCOC)(N)C(=O)OC(C)(C)C)=O DWFCQTJLYQKITB-CUNXSJBXSA-N 0.000 claims description 2
- HQGSTVLWPCLUHV-IADCTJSHSA-N C(C)OC([C@](C[C@@H](C(C)C)CC1=CC(=C(C=C1)OC)OCC1=CC=CC=C1)(N)C(=O)OC(C)(C)C)=O Chemical compound C(C)OC([C@](C[C@@H](C(C)C)CC1=CC(=C(C=C1)OC)OCC1=CC=CC=C1)(N)C(=O)OC(C)(C)C)=O HQGSTVLWPCLUHV-IADCTJSHSA-N 0.000 claims description 2
- 125000001231 benzoyloxy group Chemical group C(C1=CC=CC=C1)(=O)O* 0.000 claims description 2
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 2
- 125000003373 pyrazinyl group Chemical group 0.000 claims description 2
- 238000007142 ring opening reaction Methods 0.000 claims description 2
- OZPSKHFQVMCGMH-ICSRJNTNSA-N tert-butyl n-[(2s,4s)-4-[(4-tert-butylphenyl)methyl]-5-methyl-1-oxohexan-2-yl]carbamate Chemical compound CC(C)(C)OC(=O)N[C@H](C=O)C[C@@H](C(C)C)CC1=CC=C(C(C)(C)C)C=C1 OZPSKHFQVMCGMH-ICSRJNTNSA-N 0.000 claims description 2
- KFDRZNSEFRKMIT-PMACEKPBSA-N tert-butyl n-[(2s,4s)-4-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-5-methyl-1-oxohexan-2-yl]carbamate Chemical compound COCCCOC1=CC(C[C@@H](C[C@H](NC(=O)OC(C)(C)C)C=O)C(C)C)=CC=C1OC KFDRZNSEFRKMIT-PMACEKPBSA-N 0.000 claims description 2
- 125000004390 alkyl sulfonyl group Chemical group 0.000 claims 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims 3
- 150000001721 carbon Chemical group 0.000 claims 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 2
- IIIPAWBMXQLWIT-SFTDATJTSA-N (2s)-3,6-diethoxy-2-[(2s)-2-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-3-methylbutyl]-2,5-dihydropyrazine Chemical compound CCOC1=NCC(OCC)=N[C@H]1C[C@@H](C(C)C)CC1=CC=C(OC)C(OCCCOC)=C1 IIIPAWBMXQLWIT-SFTDATJTSA-N 0.000 claims 1
- NKWXKUZEASCOPC-MOPGFXCFSA-N (2s)-3,6-diethoxy-2-[(2s)-3-methyl-2-(phenylmethoxymethyl)butyl]-2,5-dihydropyrazine Chemical compound CCOC1=NCC(OCC)=N[C@H]1C[C@@H](C(C)C)COCC1=CC=CC=C1 NKWXKUZEASCOPC-MOPGFXCFSA-N 0.000 claims 1
- NEBTWKAKLNZFQE-CUNXSJBXSA-N C(C)(C)(C)OC(=O)[C@@](C=O)(C[C@@H](C(C)C)CC1=CC(=C(C=C1)OC)OCC1=CC=CC=C1)N Chemical compound C(C)(C)(C)OC(=O)[C@@](C=O)(C[C@@H](C(C)C)CC1=CC(=C(C=C1)OC)OCC1=CC=CC=C1)N NEBTWKAKLNZFQE-CUNXSJBXSA-N 0.000 claims 1
- GXGHKNYRWDIOEG-FNZWTVRRSA-N C(C)OC([C@](C[C@@H](C(C)C)CC1=CC(=C(C=C1)OC)OCCCOC)(N)C(=O)OC(C)(C)C)=O Chemical compound C(C)OC([C@](C[C@@H](C(C)C)CC1=CC(=C(C=C1)OC)OCCCOC)(N)C(=O)OC(C)(C)C)=O GXGHKNYRWDIOEG-FNZWTVRRSA-N 0.000 claims 1
- QCFFFBCLLZPKRB-JHOBJCJYSA-N C(C)OC([C@](C[C@@H](C(C)C)CC1=CC(=C2C(=C1)OCCO2)OCC1=CC=CC=C1)(N)C(=O)OC(C)(C)C)=O Chemical compound C(C)OC([C@](C[C@@H](C(C)C)CC1=CC(=C2C(=C1)OCCO2)OCC1=CC=CC=C1)(N)C(=O)OC(C)(C)C)=O QCFFFBCLLZPKRB-JHOBJCJYSA-N 0.000 claims 1
- GZGVVFKDTFUPBW-LULYYXHJSA-N CCC(C)[C@@H](CC1=CC(=C(C=C1)C(C)(C)C)OCCCOC)C[C@](C(=O)OCC)(C(=O)OC(C)(C)C)N Chemical compound CCC(C)[C@@H](CC1=CC(=C(C=C1)C(C)(C)C)OCCCOC)C[C@](C(=O)OCC)(C(=O)OC(C)(C)C)N GZGVVFKDTFUPBW-LULYYXHJSA-N 0.000 claims 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims 1
- MGMJMSBRMAGLTR-ROUUACIJSA-N ethyl (2s,4s)-2-amino-4-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-5-methylhexanoate Chemical compound CCOC(=O)[C@@H](N)C[C@@H](C(C)C)CC1=CC=C(OC)C(OCCCOC)=C1 MGMJMSBRMAGLTR-ROUUACIJSA-N 0.000 claims 1
- FMGIXKHNSVOGNH-MOPGFXCFSA-N ethyl (2s,4s)-5-methyl-2-[(2-methylpropan-2-yl)oxycarbonylamino]-4-(phenylmethoxymethyl)hexanoate Chemical compound CC(C)(C)OC(=O)N[C@H](C(=O)OCC)C[C@@H](C(C)C)COCC1=CC=CC=C1 FMGIXKHNSVOGNH-MOPGFXCFSA-N 0.000 claims 1
- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 claims 1
- PDBCVGAGGJBVED-CYFREDJKSA-N tert-butyl (2S,5S)-2-amino-2-hydroxy-5-[[4-methoxy-3-(3-methoxypropoxy)phenyl]methyl]-6-methylheptanoate Chemical compound C(C)(C)(C)OC(=O)[C@](CC[C@H](C(C)C)CC1=CC(=C(C=C1)OC)OCCCOC)(O)N PDBCVGAGGJBVED-CYFREDJKSA-N 0.000 claims 1
- 239000004480 active ingredient Substances 0.000 abstract description 3
- 239000002220 antihypertensive agent Substances 0.000 abstract description 3
- 229940030600 antihypertensive agent Drugs 0.000 abstract description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 148
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 133
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 83
- 239000000243 solution Substances 0.000 description 69
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 63
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 61
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 50
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 31
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 26
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 26
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 25
- 239000000741 silica gel Substances 0.000 description 25
- 229910002027 silica gel Inorganic materials 0.000 description 25
- WDYVUKGVKRZQNM-UHFFFAOYSA-N 6-phosphonohexylphosphonic acid Chemical compound OP(O)(=O)CCCCCCP(O)(O)=O WDYVUKGVKRZQNM-UHFFFAOYSA-N 0.000 description 24
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 20
- 239000011541 reaction mixture Substances 0.000 description 20
- 238000003756 stirring Methods 0.000 description 19
- 238000006243 chemical reaction Methods 0.000 description 17
- 239000012074 organic phase Substances 0.000 description 17
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 16
- 239000007858 starting material Substances 0.000 description 16
- 125000001424 substituent group Chemical group 0.000 description 15
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 14
- 239000002585 base Substances 0.000 description 14
- 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 13
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 12
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 11
- MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 10
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical group OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 10
- 238000004458 analytical method Methods 0.000 description 10
- 230000015572 biosynthetic process Effects 0.000 description 10
- 239000000460 chlorine Substances 0.000 description 10
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 10
- 235000019341 magnesium sulphate Nutrition 0.000 description 10
- 239000003921 oil Substances 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- 125000005931 tert-butyloxycarbonyl group Chemical group [H]C([H])([H])C(OC(*)=O)(C([H])([H])[H])C([H])([H])[H] 0.000 description 10
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
- KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
- PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 239000012043 crude product Substances 0.000 description 8
- 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 8
- 125000005843 halogen group Chemical group 0.000 description 8
- 239000000543 intermediate Substances 0.000 description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 8
- 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 8
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 7
- 238000001816 cooling Methods 0.000 description 7
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
- 238000004128 high performance liquid chromatography Methods 0.000 description 7
- 238000002844 melting Methods 0.000 description 7
- 230000008018 melting Effects 0.000 description 7
- 238000000746 purification Methods 0.000 description 7
- 239000007787 solid Substances 0.000 description 7
- 239000002904 solvent Substances 0.000 description 7
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 6
- 238000004364 calculation method Methods 0.000 description 6
- 239000003795 chemical substances by application Substances 0.000 description 6
- 239000003480 eluent Substances 0.000 description 6
- 239000000706 filtrate Substances 0.000 description 6
- KJIFKLIQANRMOU-UHFFFAOYSA-N oxidanium;4-methylbenzenesulfonate Chemical compound O.CC1=CC=C(S(O)(=O)=O)C=C1 KJIFKLIQANRMOU-UHFFFAOYSA-N 0.000 description 6
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 6
- 239000000725 suspension Substances 0.000 description 6
- MHAJPDPJQMAIIY-UHFFFAOYSA-N Hydrogen peroxide Chemical compound OO MHAJPDPJQMAIIY-UHFFFAOYSA-N 0.000 description 5
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
- 239000008346 aqueous phase Substances 0.000 description 5
- HQABUPZFAYXKJW-UHFFFAOYSA-N butan-1-amine Chemical compound CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 5
- 239000012141 concentrate Substances 0.000 description 5
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 5
- 239000012071 phase Substances 0.000 description 5
- 238000001953 recrystallisation Methods 0.000 description 5
- RIOQSEWOXXDEQQ-UHFFFAOYSA-N triphenylphosphine Chemical compound C1=CC=CC=C1P(C=1C=CC=CC=1)C1=CC=CC=C1 RIOQSEWOXXDEQQ-UHFFFAOYSA-N 0.000 description 5
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- 229960004418 trolamine Drugs 0.000 description 1
- 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 description 1
- 229920002554 vinyl polymer Polymers 0.000 description 1
- 229910052725 zinc Inorganic materials 0.000 description 1
- 239000011701 zinc Substances 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/22—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by carboxyl groups
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C07C229/36—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings with at least one amino group and one carboxyl group bound to the same carbon atom of the carbon skeleton
-
- 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
- C07C237/20—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 the carbon skeleton containing six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/01—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms
- C07C255/11—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound oxygen atoms bound to the same saturated acyclic carbon skeleton
- C07C255/13—Carboxylic acid nitriles having cyano groups bound to acyclic carbon atoms containing cyano groups and singly-bound oxygen atoms bound to the same saturated acyclic carbon skeleton containing cyano groups and etherified hydroxy groups bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/16—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by singly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/10—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C271/18—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atoms of the carbamate groups bound to hydrogen atoms or to acyclic carbon atoms to carbon atoms of hydrocarbon radicals substituted by doubly-bound oxygen atoms
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D241/00—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings
- C07D241/02—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings
- C07D241/06—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members
- C07D241/08—Heterocyclic compounds containing 1,4-diazine or hydrogenated 1,4-diazine rings not condensed with other rings having one or two double bonds between ring members or between ring members and non-ring members with oxygen atoms directly attached to ring carbon atoms
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
- Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
- Y02P20/00—Technologies relating to chemical industry
- Y02P20/50—Improvements relating to the production of bulk chemicals
- Y02P20/55—Design of synthesis routes, e.g. reducing the use of auxiliary or protecting groups
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Plural Heterocyclic Compounds (AREA)
- Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)
Applications Claiming Priority (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
CH116994 | 1994-04-18 | ||
CH01169/94-3 | 1994-04-18 | ||
CH24795 | 1995-01-30 | ||
CH00247/95-0 | 1995-01-30 |
Publications (1)
Publication Number | Publication Date |
---|---|
JPH0827079A true JPH0827079A (ja) | 1996-01-30 |
Family
ID=25684018
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
JP7092827A Pending JPH0827079A (ja) | 1994-04-18 | 1995-04-18 | アルファ−アミノアルカン酸及還元生成物 |
Country Status (10)
Country | Link |
---|---|
US (1) | US5659065A (en, 2012) |
EP (1) | EP0678500A1 (en, 2012) |
JP (1) | JPH0827079A (en, 2012) |
KR (1) | KR950032072A (en, 2012) |
AU (1) | AU1642395A (en, 2012) |
CA (1) | CA2147044A1 (en, 2012) |
FI (1) | FI951773A7 (en, 2012) |
IL (1) | IL113384A0 (en, 2012) |
NO (1) | NO951443L (en, 2012) |
NZ (1) | NZ270938A (en, 2012) |
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004502663A (ja) * | 2000-07-03 | 2004-01-29 | シュペーデル・ファルマ・アーゲー | (r)−2−アルキル−3−フェニルプロピオン酸の調製 |
JP2007529474A (ja) * | 2004-03-19 | 2007-10-25 | シュペーデル・エクスペリメンタ・アーゲー | 高血圧の処置のためのレニン阻害剤としての5−アミノ−4−ヒドロキシ−7−(1h−インドールメチル)−8−メチルノンアミド誘導体 |
JP2008523035A (ja) * | 2004-12-10 | 2008-07-03 | シュペーデル・エクスペリメンタ・アーゲー | ω−フェニルオクタンアミド |
JP2009507899A (ja) * | 2005-09-17 | 2009-02-26 | シュペーデル・エクスペリメンタ・アーゲー | 飽和o−複素環により置換されたアルカン酸アミド |
Families Citing this family (21)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
WO1995008530A1 (fr) * | 1993-09-20 | 1995-03-30 | Kaneka Corporation | Procede de production d'un derive de 3-amino-2-hydroxy-1-propanol |
WO2002002508A1 (en) * | 2000-07-05 | 2002-01-10 | Speedel Pharma Ag | Process for the preparation of substituted octanoyl amides |
JP4853888B2 (ja) * | 2000-07-25 | 2012-01-11 | ノバルティス ファーマ アーゲー | 置換オクタノイルアミドの調製方法 |
US8168616B1 (en) | 2000-11-17 | 2012-05-01 | Novartis Ag | Combination comprising a renin inhibitor and an angiotensin receptor inhibitor for hypertension |
GB0212410D0 (en) * | 2002-05-29 | 2002-07-10 | Novartis Ag | Organic compounds |
GB0327839D0 (en) * | 2003-12-01 | 2003-12-31 | Novartis Ag | Organic compounds |
CN1934082A (zh) * | 2004-03-19 | 2007-03-21 | 斯皮德尔实验股份公司 | 有机化合物 |
GB0511686D0 (en) * | 2005-06-08 | 2005-07-13 | Novartis Ag | Organic compounds |
GB0521083D0 (en) * | 2005-10-17 | 2005-11-23 | Novartis Ag | Organic compounds |
GB2431654A (en) * | 2005-10-25 | 2007-05-02 | Novartis Ag | Alternative synthesis of aryl-octanoyl amide compounds |
GB2431643A (en) * | 2005-10-25 | 2007-05-02 | Novartis Ag | Synthesis of aryl-octanoyl amide compounds |
GB2431651A (en) * | 2005-10-25 | 2007-05-02 | Novartis Ag | Synthesis of aryl-octanoyl amide compounds |
GB2431647A (en) * | 2005-10-25 | 2007-05-02 | Novartis Ag | Synthesis of aryl-octanoyl amide compounds |
GB2431644A (en) * | 2005-10-25 | 2007-05-02 | Novartis Ag | Synthesis of aryl-octanoyl amide compounds |
GB2431652A (en) * | 2005-10-25 | 2007-05-02 | Novartis Ag | Alternative synthesis of aryl-octanoyl amide compounds |
GB2431650A (en) * | 2005-10-25 | 2007-05-02 | Novartis Ag | Alternative synthesis of aryl-octanoyl amide compounds |
GB2431642A (en) * | 2005-10-25 | 2007-05-02 | Novartis Ag | Alternative synthesis of aryl-octanoyl amide compounds |
GB0605688D0 (en) * | 2006-03-21 | 2006-05-03 | Novartis Ag | Organic compounds |
JP2009532494A (ja) * | 2006-04-03 | 2009-09-10 | ノバルティス アクチエンゲゼルシャフト | 高血圧処置のためのレニン阻害剤 |
US8338620B2 (en) * | 2007-04-03 | 2012-12-25 | Novartis Ag | Methods for the production of C-8 lactam lactone compounds |
WO2013171767A1 (en) | 2012-05-18 | 2013-11-21 | Mylan Laboratories Limited | An improved process for the preparation of aliskiren |
Family Cites Families (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
CH427841A (de) * | 1959-08-24 | 1967-01-15 | Ciba Geigy | Verfahren zur Herstellung von a-(w-Aminoalkyl)-a-aminoessigsäuregruppenhaltigen Peptiden |
US3988341A (en) * | 1974-06-25 | 1976-10-26 | Merck & Co., Inc. | Esterification process |
-
1995
- 1995-04-04 US US08/416,240 patent/US5659065A/en not_active Expired - Fee Related
- 1995-04-07 EP EP95810238A patent/EP0678500A1/de not_active Withdrawn
- 1995-04-12 NO NO951443A patent/NO951443L/no unknown
- 1995-04-12 AU AU16423/95A patent/AU1642395A/en not_active Abandoned
- 1995-04-12 FI FI951773A patent/FI951773A7/fi not_active Application Discontinuation
- 1995-04-13 CA CA002147044A patent/CA2147044A1/en not_active Abandoned
- 1995-04-13 NZ NZ270938A patent/NZ270938A/en unknown
- 1995-04-14 IL IL11338495A patent/IL113384A0/xx unknown
- 1995-04-17 KR KR1019950008958A patent/KR950032072A/ko not_active Withdrawn
- 1995-04-18 JP JP7092827A patent/JPH0827079A/ja active Pending
Cited By (4)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JP2004502663A (ja) * | 2000-07-03 | 2004-01-29 | シュペーデル・ファルマ・アーゲー | (r)−2−アルキル−3−フェニルプロピオン酸の調製 |
JP2007529474A (ja) * | 2004-03-19 | 2007-10-25 | シュペーデル・エクスペリメンタ・アーゲー | 高血圧の処置のためのレニン阻害剤としての5−アミノ−4−ヒドロキシ−7−(1h−インドールメチル)−8−メチルノンアミド誘導体 |
JP2008523035A (ja) * | 2004-12-10 | 2008-07-03 | シュペーデル・エクスペリメンタ・アーゲー | ω−フェニルオクタンアミド |
JP2009507899A (ja) * | 2005-09-17 | 2009-02-26 | シュペーデル・エクスペリメンタ・アーゲー | 飽和o−複素環により置換されたアルカン酸アミド |
Also Published As
Publication number | Publication date |
---|---|
NO951443L (en, 2012) | 1995-10-19 |
FI951773A0 (fi) | 1995-04-12 |
IL113384A0 (en) | 1995-07-31 |
CA2147044A1 (en) | 1995-10-19 |
NO951443D0 (en, 2012) | 1995-04-12 |
FI951773A7 (fi) | 1995-10-19 |
US5659065A (en) | 1997-08-19 |
EP0678500A1 (de) | 1995-10-25 |
AU1642395A (en) | 1995-10-26 |
NZ270938A (en) | 1996-11-26 |
KR950032072A (ko) | 1995-12-20 |
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