BRPI0621969A2 - piperidinas substituìdas, bem como uso das mesmas e preparação farmacêutica - Google Patents

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Publication number

BRPI0621969A2

BRPI0621969A2 BRPI0621969-1A BRPI0621969A BRPI0621969A2 BR PI0621969 A2 BRPI0621969 A2 BR PI0621969A2 BR PI0621969 A BRPI0621969 A BR PI0621969A BR PI0621969 A2 BRPI0621969 A2 BR PI0621969A2

Authority

BR

Brazil

Prior art keywords

methoxy

alkyl

alkoxy

phenyl

propyl

Prior art date

2005-03-31

Links

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• 239000000825 pharmaceutical preparation Substances 0.000 title claims abstract description 7
• 150000003053 piperidines Chemical class 0.000 title abstract description 6
• 150000001875 compounds Chemical class 0.000 claims abstract description 445
• -1 acenaphthyl Chemical group 0.000 claims description 1044
• 125000000217 alkyl group Chemical group 0.000 claims description 128
• 125000003545 alkoxy group Chemical group 0.000 claims description 99
• 150000003839 salts Chemical class 0.000 claims description 46
• 229910052739 hydrogen Inorganic materials 0.000 claims description 36
• 239000001257 hydrogen Substances 0.000 claims description 36
• 229910052757 nitrogen Inorganic materials 0.000 claims description 36
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 33
• 229910052736 halogen Inorganic materials 0.000 claims description 24
• 150000002367 halogens Chemical class 0.000 claims description 24
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 24
• 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 22
• 125000003118 aryl group Chemical group 0.000 claims description 20
• 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 20
• 125000001424 substituent group Chemical group 0.000 claims description 20
• 229910052760 oxygen Inorganic materials 0.000 claims description 19
• 125000004414 alkyl thio group Chemical group 0.000 claims description 18
• 229910052799 carbon Inorganic materials 0.000 claims description 18
• 239000001301 oxygen Substances 0.000 claims description 17
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 15
• 229920006395 saturated elastomer Polymers 0.000 claims description 15
• 229910052717 sulfur Inorganic materials 0.000 claims description 15
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 14
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 14
• 125000005059 halophenyl group Chemical group 0.000 claims description 14
• 125000000623 heterocyclic group Chemical group 0.000 claims description 13
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 13
• 125000002252 acyl group Chemical group 0.000 claims description 12
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 11
• 125000004043 oxo group Chemical group O=* 0.000 claims description 11
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 9
• 125000001624 naphthyl group Chemical group 0.000 claims description 9
• 125000004076 pyridyl group Chemical group 0.000 claims description 9
• 239000011593 sulfur Chemical group 0.000 claims description 9
• 125000004434 sulfur atom Chemical group 0.000 claims description 9
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 9
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical group C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 claims description 8
• 239000005977 Ethylene Substances 0.000 claims description 8
• 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 8
• 125000002947 alkylene group Chemical group 0.000 claims description 8
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims description 8
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 7
• 125000003302 alkenyloxy group Chemical group 0.000 claims description 7
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 7
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 7
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 6
• 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 6
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 6
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 6
• 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 description 6
• 125000005842 heteroatom Chemical group 0.000 claims description 6
• 229940002612 prodrug Drugs 0.000 claims description 6
• 239000000651 prodrug Substances 0.000 claims description 6
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
• 125000001544 thienyl group Chemical group 0.000 claims description 6
• 125000006625 (C3-C8) cycloalkyloxy group Chemical group 0.000 claims description 5
• 125000004450 alkenylene group Chemical group 0.000 claims description 5
• 125000004448 alkyl carbonyl group Chemical group 0.000 claims description 5
• 125000004429 atom Chemical group 0.000 claims description 5
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 5
• 239000003814 drug Substances 0.000 claims description 5
• 238000002360 preparation method Methods 0.000 claims description 5
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 5
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 5
• 125000002373 5 membered heterocyclic group Chemical group 0.000 claims description 4
• 125000004070 6 membered heterocyclic group Chemical group 0.000 claims description 4
• 208000010496 Heart Arrest Diseases 0.000 claims description 4
• 206010020772 Hypertension Diseases 0.000 claims description 4
• 125000002541 furyl group Chemical group 0.000 claims description 4
• 125000002883 imidazolyl group Chemical group 0.000 claims description 4
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 4
• 125000001425 triazolyl group Chemical group 0.000 claims description 4
• 208000010412 Glaucoma Diseases 0.000 claims description 3
• 208000001647 Renal Insufficiency Diseases 0.000 claims description 3
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 3
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 3
• 125000004181 carboxyalkyl group Chemical group 0.000 claims description 3
• 201000006370 kidney failure Diseases 0.000 claims description 3
• 125000002971 oxazolyl group Chemical group 0.000 claims description 3
• 230000002265 prevention Effects 0.000 claims description 3
• 208000037803 restenosis Diseases 0.000 claims description 3
• 101100509371 Arabidopsis thaliana CHR11 gene Proteins 0.000 claims description 2
• 206010061216 Infarction Diseases 0.000 claims description 2
• 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 2
• 125000005331 diazinyl group Chemical group N1=NC(=CC=C1)* 0.000 claims description 2
• 125000004415 heterocyclylalkyl group Chemical group 0.000 claims description 2
• 230000007574 infarction Effects 0.000 claims description 2
• 230000002285 radioactive effect Effects 0.000 claims description 2
• 150000001721 carbon Chemical group 0.000 claims 6
• 208000006011 Stroke Diseases 0.000 claims 2
• 125000003161 (C1-C6) alkylene group Chemical group 0.000 claims 1
• 125000006577 C1-C6 hydroxyalkyl group Chemical group 0.000 claims 1
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims 1
• 206010010071 Coma Diseases 0.000 claims 1
• 125000003342 alkenyl group Chemical group 0.000 claims 1
• 125000005160 aryl oxy alkyl group Chemical group 0.000 claims 1
• 229920001577 copolymer Chemical group 0.000 claims 1
• 239000002461 renin inhibitor Substances 0.000 abstract description 7
• 229940086526 renin-inhibitors Drugs 0.000 abstract description 6
• 230000003389 potentiating effect Effects 0.000 abstract description 2
• 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 507
• 238000000034 method Methods 0.000 description 225
• 239000002253 acid Substances 0.000 description 163
• DEQYTNZJHKPYEZ-UHFFFAOYSA-N ethyl acetate;heptane Chemical compound CCOC(C)=O.CCCCCCC DEQYTNZJHKPYEZ-UHFFFAOYSA-N 0.000 description 156
• 239000000243 solution Substances 0.000 description 153
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 152
• 239000003921 oil Substances 0.000 description 146
• 235000019198 oils Nutrition 0.000 description 146
• 239000000203 mixture Substances 0.000 description 129
• 239000011541 reaction mixture Substances 0.000 description 114
• 239000007858 starting material Substances 0.000 description 111
• 238000003818 flash chromatography Methods 0.000 description 103
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 96
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 90
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 88
• 229910052681 coesite Inorganic materials 0.000 description 78
• 229910052906 cristobalite Inorganic materials 0.000 description 78
• 229910052682 stishovite Inorganic materials 0.000 description 78
• 229910052905 tridymite Inorganic materials 0.000 description 78
• 239000000377 silicon dioxide Substances 0.000 description 74
• 235000012239 silicon dioxide Nutrition 0.000 description 74
• 239000012074 organic phase Substances 0.000 description 65
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 55
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 55
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 54
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 52
• 229910052938 sodium sulfate Inorganic materials 0.000 description 52
• 235000011152 sodium sulphate Nutrition 0.000 description 52
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 50
• 150000002148 esters Chemical class 0.000 description 47
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 43
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 42
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 42
• 239000012230 colorless oil Substances 0.000 description 39
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 37
• WGLUMOCWFMKWIL-UHFFFAOYSA-N dichloromethane;methanol Chemical compound OC.ClCCl WGLUMOCWFMKWIL-UHFFFAOYSA-N 0.000 description 37
• 235000019439 ethyl acetate Nutrition 0.000 description 35
• 229940098779 methanesulfonic acid Drugs 0.000 description 33
• 125000004574 piperidin-2-yl group Chemical group N1C(CCCC1)* 0.000 description 33
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 30
• ZMXDDKWLCZADIW-UHFFFAOYSA-N dimethylformamide Substances CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 28
• 150000003254 radicals Chemical class 0.000 description 28
• BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 26
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 24
• 239000007787 solid Substances 0.000 description 23
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 21
• 150000004702 methyl esters Chemical class 0.000 description 21
• 239000012044 organic layer Substances 0.000 description 21
• 239000006260 foam Substances 0.000 description 19
• NXFFJDQHYLNEJK-UHFFFAOYSA-N 2-[4-[(4-chlorophenyl)methyl]-7-fluoro-5-methylsulfonyl-2,3-dihydro-1h-cyclopenta[b]indol-3-yl]acetic acid Chemical compound C1=2C(S(=O)(=O)C)=CC(F)=CC=2C=2CCC(CC(O)=O)C=2N1CC1=CC=C(Cl)C=C1 NXFFJDQHYLNEJK-UHFFFAOYSA-N 0.000 description 17
• 230000008569 process Effects 0.000 description 16
• 229910004298 SiO 2 Inorganic materials 0.000 description 15
• 239000012267 brine Substances 0.000 description 15
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 15
• DNUTZBZXLPWRJG-UHFFFAOYSA-N 1-Piperidine carboxylic acid Chemical compound OC(=O)N1CCCCC1 DNUTZBZXLPWRJG-UHFFFAOYSA-N 0.000 description 12
• 229910021529 ammonia Inorganic materials 0.000 description 12
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 12
• 239000002904 solvent Substances 0.000 description 12
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 11
• HYTACLVSJIFYBY-UHFFFAOYSA-N azane;dichloromethane;methanol Chemical compound N.OC.ClCCl HYTACLVSJIFYBY-UHFFFAOYSA-N 0.000 description 11
• 125000004494 ethyl ester group Chemical group 0.000 description 11
• 150000002431 hydrogen Chemical class 0.000 description 11
• 229940080818 propionamide Drugs 0.000 description 11
• 239000000126 substance Substances 0.000 description 11
• 239000000725 suspension Substances 0.000 description 11
• ROSDSFDQCJNGOL-UHFFFAOYSA-N Dimethylamine Chemical compound CNC ROSDSFDQCJNGOL-UHFFFAOYSA-N 0.000 description 10
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 10
• 125000004432 carbon atom Chemical group C* 0.000 description 10
• SMCWNPAVVQIDBM-UHFFFAOYSA-N piperidine-1,2-dicarboxylic acid Chemical compound OC(=O)C1CCCCN1C(O)=O SMCWNPAVVQIDBM-UHFFFAOYSA-N 0.000 description 10
• 239000012312 sodium hydride Substances 0.000 description 10
• 229910000104 sodium hydride Inorganic materials 0.000 description 10
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 9
• DLFVBJFMPXGRIB-UHFFFAOYSA-N Acetamide Chemical compound CC(N)=O DLFVBJFMPXGRIB-UHFFFAOYSA-N 0.000 description 9
• 230000015572 biosynthetic process Effects 0.000 description 9
• 238000006243 chemical reaction Methods 0.000 description 9
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
• INQOMBQAUSQDDS-UHFFFAOYSA-N iodomethane Chemical compound IC INQOMBQAUSQDDS-UHFFFAOYSA-N 0.000 description 9
• YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 8
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 8
• 238000012360 testing method Methods 0.000 description 8
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 7
• 150000005840 aryl radicals Chemical class 0.000 description 7
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 7
• 125000002757 morpholinyl group Chemical group 0.000 description 7
• HXEACLLIILLPRG-UHFFFAOYSA-N pipecolic acid Chemical compound OC(=O)C1CCCCN1 HXEACLLIILLPRG-UHFFFAOYSA-N 0.000 description 7
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 7
• 238000000746 purification Methods 0.000 description 7
• YZUPZGFPHUVJKC-UHFFFAOYSA-N 1-bromo-2-methoxyethane Chemical compound COCCBr YZUPZGFPHUVJKC-UHFFFAOYSA-N 0.000 description 6
• YYROPELSRYBVMQ-UHFFFAOYSA-N 4-toluenesulfonyl chloride Chemical compound CC1=CC=C(S(Cl)(=O)=O)C=C1 YYROPELSRYBVMQ-UHFFFAOYSA-N 0.000 description 6
• 101800000734 Angiotensin-1 Proteins 0.000 description 6
• 102400000344 Angiotensin-1 Human genes 0.000 description 6
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 6
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 6
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 6
• NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 6
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
• 150000001412 amines Chemical class 0.000 description 6
• ORWYRWWVDCYOMK-HBZPZAIKSA-N angiotensin I Chemical compound C([C@@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N1[C@@H](CCC1)C(=O)N[C@@H](CC=1C=CC=CC=1)C(=O)N[C@@H](CC=1NC=NC=1)C(=O)N[C@@H](CC(C)C)C(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CCCN=C(N)N)NC(=O)[C@@H](N)CC(O)=O)C(C)C)C1=CC=C(O)C=C1 ORWYRWWVDCYOMK-HBZPZAIKSA-N 0.000 description 6
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 description 6
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
• 239000012043 crude product Substances 0.000 description 6
• 239000003112 inhibitor Substances 0.000 description 6
• NXPHGHWWQRMDIA-UHFFFAOYSA-M magnesium;carbanide;bromide Chemical compound [CH3-].[Mg+2].[Br-] NXPHGHWWQRMDIA-UHFFFAOYSA-M 0.000 description 6
• 239000000546 pharmaceutical excipient Substances 0.000 description 6
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 6
• 239000003826 tablet Substances 0.000 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 description 6
• BQLHMMQUVJCTAN-UHFFFAOYSA-N 1-chloro-3-methoxypropane Chemical compound COCCCCl BQLHMMQUVJCTAN-UHFFFAOYSA-N 0.000 description 5
• PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 description 5
• 125000000850 2H-chromenyl group Chemical group O1C(C=CC2=CC=CC=C12)* 0.000 description 5
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 5
• 239000005711 Benzoic acid Substances 0.000 description 5
• COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 5
• VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 5
• QUSNBJAOOMFDIB-UHFFFAOYSA-N Ethylamine Chemical group CCN QUSNBJAOOMFDIB-UHFFFAOYSA-N 0.000 description 5
• 125000004453 alkoxycarbonyl group Chemical group 0.000 description 5
• 125000003806 alkyl carbonyl amino group Chemical group 0.000 description 5
• 125000005605 benzo group Chemical group 0.000 description 5
• 230000036772 blood pressure Effects 0.000 description 5
• UWTDFICHZKXYAC-UHFFFAOYSA-N boron;oxolane Chemical compound [B].C1CCOC1 UWTDFICHZKXYAC-UHFFFAOYSA-N 0.000 description 5
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
• HXEACLLIILLPRG-RXMQYKEDSA-N l-pipecolic acid Natural products OC(=O)[C@H]1CCCCN1 HXEACLLIILLPRG-RXMQYKEDSA-N 0.000 description 5
• 125000005476 oxopyrrolidinyl group Chemical group 0.000 description 5
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 5
• 125000003386 piperidinyl group Chemical group 0.000 description 5
• 125000000719 pyrrolidinyl group Chemical group 0.000 description 5
• 238000000926 separation method Methods 0.000 description 5
• 229910052708 sodium Inorganic materials 0.000 description 5
• 239000011734 sodium Substances 0.000 description 5
• 238000003756 stirring Methods 0.000 description 5
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 5
• 125000004568 thiomorpholinyl group Chemical group 0.000 description 5
• JCGJFSMJODBMFD-QIZGOQQVSA-N (2r)-1-[(2r,4r,5r)-4-(4-methoxyphenyl)-5-[[4-(3-methoxypropyl)-2,3-dihydro-1,4-benzoxazin-6-yl]methoxy]-1-(4-methylphenyl)sulfonylpiperidin-2-yl]propan-2-amine Chemical compound C1([C@H]2C[C@H](C[C@@H](C)N)N(C[C@@H]2OCC2=CC=C3OCCN(C3=C2)CCCOC)S(=O)(=O)C=2C=CC(C)=CC=2)=CC=C(OC)C=C1 JCGJFSMJODBMFD-QIZGOQQVSA-N 0.000 description 4
• 125000000143 2-carboxyethyl group Chemical group [H]OC(=O)C([H])([H])C([H])([H])* 0.000 description 4
• BCHZICNRHXRCHY-UHFFFAOYSA-N 2h-oxazine Chemical compound N1OC=CC=C1 BCHZICNRHXRCHY-UHFFFAOYSA-N 0.000 description 4
• VLPIGVSFEJSWRE-YBAOVTMCSA-N 6-[[(3r,4r,6s)-6-(bromomethyl)-4-(4-methoxyphenyl)-1-(4-methylphenyl)sulfonylpiperidin-3-yl]oxymethyl]-4-(3-methoxypropyl)-2,3-dihydro-1,4-benzoxazine Chemical compound C1([C@H]2C[C@@H](CBr)N(C[C@@H]2OCC2=CC=C3OCCN(C3=C2)CCCOC)S(=O)(=O)C=2C=CC(C)=CC=2)=CC=C(OC)C=C1 VLPIGVSFEJSWRE-YBAOVTMCSA-N 0.000 description 4
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