HRP950609A2 - Piperazine derivatives, medicaments containing the same, their use and processes for preparing the same - Google Patents

Info

Publication number

HRP950609A2

HRP950609A2 HR19533639.9A HRP950609A HRP950609A2 HR P950609 A2 HRP950609 A2 HR P950609A2 HR P950609 A HRP950609 A HR P950609A HR P950609 A2 HRP950609 A2 HR P950609A2

Authority

HR

Croatia

Prior art keywords

group

alkyl

piperidinyl

piperazin

acid

Prior art date

1994-12-23

Links

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• 238000000034 method Methods 0.000 title claims description 11
• 150000004885 piperazines Chemical class 0.000 title claims description 9
• 229940066771 systemic antihistamines piperazine derivative Drugs 0.000 title claims description 9
• 239000003814 drug Substances 0.000 title claims description 5
• 230000008569 process Effects 0.000 title claims description 3
• -1 C1-3-alkoxycarbonyl Chemical group 0.000 claims description 164
• 125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 159
• 150000001875 compounds Chemical class 0.000 claims description 103
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 101
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 93
• 125000004432 carbon atom Chemical group C* 0.000 claims description 68
• 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 67
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 64
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 62
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 60
• 238000006243 chemical reaction Methods 0.000 claims description 49
• 230000002829 reductive effect Effects 0.000 claims description 49
• 229910052757 nitrogen Inorganic materials 0.000 claims description 43
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 42
• 125000000217 alkyl group Chemical group 0.000 claims description 37
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 35
• 239000002253 acid Substances 0.000 claims description 32
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 32
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 32
• XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 claims description 31
• 239000000203 mixture Substances 0.000 claims description 29
• 150000003839 salts Chemical class 0.000 claims description 29
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 25
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 25
• 238000002360 preparation method Methods 0.000 claims description 25
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 24
• 229910052740 iodine Inorganic materials 0.000 claims description 24
• 125000003118 aryl group Chemical group 0.000 claims description 23
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 21
• 229910052799 carbon Inorganic materials 0.000 claims description 18
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 18
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 17
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
• 125000000843 phenylene group Chemical group C1(=C(C=CC=C1)*)* 0.000 claims description 16
• 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 15
• 125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 claims description 14
• 125000004956 cyclohexylene group Chemical group 0.000 claims description 12
• 150000002148 esters Chemical class 0.000 claims description 12
• 238000001727 in vivo Methods 0.000 claims description 12
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 11
• 125000003545 alkoxy group Chemical group 0.000 claims description 11
• 125000001841 imino group Chemical group [H]N=* 0.000 claims description 11
• 235000019260 propionic acid Nutrition 0.000 claims description 11
• IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 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 10
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims description 10
• 125000004076 pyridyl group Chemical group 0.000 claims description 10
• 230000000269 nucleophilic effect Effects 0.000 claims description 9
• 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims description 8
• 125000004955 1,4-cyclohexylene group Chemical group [H]C1([H])C([H])([H])C([H])([*:1])C([H])([H])C([H])([H])C1([H])[*:2] 0.000 claims description 8
• 125000001140 1,4-phenylene group Chemical group [H]C1=C([H])C([*:2])=C([H])C([H])=C1[*:1] 0.000 claims description 8
• 235000001014 amino acid Nutrition 0.000 claims description 8
• 150000001413 amino acids Chemical class 0.000 claims description 8
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 8
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 8
• 150000001602 bicycloalkyls Chemical group 0.000 claims description 8
• GCFAUZGWPDYAJN-UHFFFAOYSA-N cyclohexyl 3-phenylprop-2-enoate Chemical compound C=1C=CC=CC=1C=CC(=O)OC1CCCCC1 GCFAUZGWPDYAJN-UHFFFAOYSA-N 0.000 claims description 8
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
• 125000002485 formyl group Chemical group [H]C(*)=O 0.000 claims description 7
• 125000006526 (C1-C2) alkyl group Chemical group 0.000 claims description 6
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims description 6
• 125000002030 1,2-phenylene group Chemical group [H]C1=C([H])C([*:1])=C([*:2])C([H])=C1[H] 0.000 claims description 6
• 239000005977 Ethylene Substances 0.000 claims description 6
• 125000002252 acyl group Chemical group 0.000 claims description 6
• 125000003342 alkenyl group Chemical group 0.000 claims description 6
• 125000000304 alkynyl group Chemical group 0.000 claims description 6
• 150000001412 amines Chemical class 0.000 claims description 6
• 125000003277 amino group Chemical group 0.000 claims description 6
• 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 claims description 6
• 229910052794 bromium Inorganic materials 0.000 claims description 6
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 6
• 229910052801 chlorine Inorganic materials 0.000 claims description 6
• 239000000460 chlorine Substances 0.000 claims description 6
• 125000000392 cycloalkenyl group Chemical group 0.000 claims description 6
• 125000003884 phenylalkyl group Chemical group 0.000 claims description 6
• 125000003170 phenylsulfonyl group Chemical group C1(=CC=CC=C1)S(=O)(=O)* 0.000 claims description 6
• 125000001424 substituent group Chemical group 0.000 claims description 6
• BNPJOIFXNVGADN-UHFFFAOYSA-N 2-[4-[(4-piperidin-4-ylpiperazine-1-carbonyl)amino]phenoxy]acetic acid Chemical compound C1=CC(OCC(=O)O)=CC=C1NC(=O)N1CCN(C2CCNCC2)CC1 BNPJOIFXNVGADN-UHFFFAOYSA-N 0.000 claims description 5
• ZCYVEMRRCGMTRW-UHFFFAOYSA-N 7553-56-2 Chemical group [I] ZCYVEMRRCGMTRW-UHFFFAOYSA-N 0.000 claims description 5
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 5
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 5
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 5
• 230000007062 hydrolysis Effects 0.000 claims description 5
• 238000006460 hydrolysis reaction Methods 0.000 claims description 5
• 125000006559 (C1-C3) alkylamino group Chemical group 0.000 claims description 4
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 4
• 125000006272 (C3-C7) cycloalkyl group Chemical group 0.000 claims description 4
• 101100294102 Caenorhabditis elegans nhr-2 gene Proteins 0.000 claims description 4
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 4
• 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 4
• LEQAOMBKQFMDFZ-UHFFFAOYSA-N glyoxal Chemical compound O=CC=O LEQAOMBKQFMDFZ-UHFFFAOYSA-N 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 4
• 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 4
• 125000006239 protecting group Chemical group 0.000 claims description 4
• 125000005551 pyridylene group Chemical group 0.000 claims description 4
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 4
• 125000006698 (C1-C3) dialkylamino group Chemical group 0.000 claims description 3
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 3
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 3
• 238000007327 hydrogenolysis reaction Methods 0.000 claims description 3
• 150000007522 mineralic acids Chemical class 0.000 claims description 3
• 150000007524 organic acids Chemical class 0.000 claims description 3
• 235000005985 organic acids Nutrition 0.000 claims description 3
• 238000001149 thermolysis Methods 0.000 claims description 3
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 2
• 125000006704 (C5-C6) cycloalkyl group Chemical group 0.000 claims description 2
• NDZFNTHGIIQMQI-UHFFFAOYSA-N 1-benzylpyridin-1-ium Chemical group C=1C=CC=C[N+]=1CC1=CC=CC=C1 NDZFNTHGIIQMQI-UHFFFAOYSA-N 0.000 claims description 2
• DHQHLYLHMXCVNZ-UHFFFAOYSA-N 3-[1-(4-piperidin-4-ylpiperazine-1-carbonyl)piperidin-4-yl]oxypropanoic acid Chemical compound C1CC(OCCC(=O)O)CCN1C(=O)N1CCN(C2CCNCC2)CC1 DHQHLYLHMXCVNZ-UHFFFAOYSA-N 0.000 claims description 2
• HTWMCCBHJPNIGR-UHFFFAOYSA-N 3-[[4-(4-piperidin-4-ylpiperazine-1-carbonyl)piperidin-1-yl]amino]propanoic acid Chemical compound N1CCC(CC1)N1CCN(CC1)C(=O)C1CCN(CC1)NCCC(=O)O HTWMCCBHJPNIGR-UHFFFAOYSA-N 0.000 claims description 2
• CMZYQGKFUWWEDM-UHFFFAOYSA-N 4-[1-(4-piperidin-4-ylpiperazine-1-carbonyl)piperidin-4-yl]butanoic acid Chemical compound C1CC(CCCC(=O)O)CCN1C(=O)N1CCN(C2CCNCC2)CC1 CMZYQGKFUWWEDM-UHFFFAOYSA-N 0.000 claims description 2
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 2
• MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 2
• 150000004260 O,O-acetals Chemical class 0.000 claims description 2
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 2
• 125000005236 alkanoylamino group Chemical group 0.000 claims description 2
• 125000003302 alkenyloxy group Chemical group 0.000 claims description 2
• 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 2
• 125000005036 alkoxyphenyl group Chemical group 0.000 claims description 2
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 2
• 125000003282 alkyl amino group Chemical group 0.000 claims description 2
• 235000008206 alpha-amino acids Nutrition 0.000 claims description 2
• 125000004391 aryl sulfonyl group Chemical group 0.000 claims description 2
• 125000004063 butyryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
• 125000004465 cycloalkenyloxy group Chemical group 0.000 claims description 2
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 2
• 125000005112 cycloalkylalkoxy group Chemical group 0.000 claims description 2
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 2
• 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 2
• 230000006806 disease prevention Effects 0.000 claims description 2
• 229940079593 drug Drugs 0.000 claims description 2
• FPIQZBQZKBKLEI-UHFFFAOYSA-N ethyl 1-[[2-chloroethyl(nitroso)carbamoyl]amino]cyclohexane-1-carboxylate Chemical compound ClCCN(N=O)C(=O)NC1(C(=O)OCC)CCCCC1 FPIQZBQZKBKLEI-UHFFFAOYSA-N 0.000 claims description 2
• 125000002534 ethynyl group Chemical group [H]C#C* 0.000 claims description 2
• 229910052731 fluorine Inorganic materials 0.000 claims description 2
• 239000011737 fluorine Substances 0.000 claims description 2
• ZHNUHDYFZUAESO-UHFFFAOYSA-N formamide Substances NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 claims description 2
• 229940015043 glyoxal Drugs 0.000 claims description 2
• 125000003104 hexanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
• 230000003993 interaction Effects 0.000 claims description 2
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
• 125000005928 isopropyloxycarbonyl group Chemical group [H]C([H])([H])C([H])(OC(*)=O)C([H])([H])[H] 0.000 claims description 2
• 150000002576 ketones Chemical class 0.000 claims description 2
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 2
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
• 229910052760 oxygen Inorganic materials 0.000 claims description 2
• 239000001301 oxygen Substances 0.000 claims description 2
• 125000001148 pentyloxycarbonyl group Chemical group 0.000 claims description 2
• 125000002071 phenylalkoxy group Chemical group 0.000 claims description 2
• 125000004742 propyloxycarbonyl group Chemical group 0.000 claims description 2
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 2
• 125000003774 valeryl group Chemical group O=C([*])C([H])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 2
• 229920002554 vinyl polymer Polymers 0.000 claims description 2
• 239000000969 carrier Substances 0.000 claims 2
• BXWVIIXLVUQTCG-UHFFFAOYSA-N 2-[4-[2-(4-piperidin-4-ylpiperazin-1-yl)acetyl]phenoxy]acetic acid Chemical compound C1=CC(OCC(=O)O)=CC=C1C(=O)CN1CCN(C2CCNCC2)CC1 BXWVIIXLVUQTCG-UHFFFAOYSA-N 0.000 claims 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 942
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 891
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• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 252
• 239000000741 silica gel Substances 0.000 description 252
• 229910002027 silica gel Inorganic materials 0.000 description 252
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 159
• 229910021529 ammonia Inorganic materials 0.000 description 156
• 238000001819 mass spectrum Methods 0.000 description 147
• 239000000243 solution Substances 0.000 description 136
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 128
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 119
• 238000002844 melting Methods 0.000 description 104
• 230000008018 melting Effects 0.000 description 104
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 102
• 150000004702 methyl esters Chemical class 0.000 description 86
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 82
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 78
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 75
• 239000002904 solvent Substances 0.000 description 66
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 65
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 57
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 56
• 238000000354 decomposition reaction Methods 0.000 description 54
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 52
• 235000002639 sodium chloride Nutrition 0.000 description 49
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 44
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 41
• 238000005984 hydrogenation reaction Methods 0.000 description 41
• 229960000583 acetic acid Drugs 0.000 description 39
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 39
• 235000019439 ethyl acetate Nutrition 0.000 description 37
• 239000007787 solid Substances 0.000 description 36
• 239000000126 substance Substances 0.000 description 35
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 33
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 32
• 239000001257 hydrogen Substances 0.000 description 32
• 229910052739 hydrogen Inorganic materials 0.000 description 32
• 239000011780 sodium chloride Substances 0.000 description 31
• 239000003054 catalyst Substances 0.000 description 28
• 239000003921 oil Substances 0.000 description 27
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 26
• 238000003756 stirring Methods 0.000 description 26
• NZNMSOFKMUBTKW-UHFFFAOYSA-N cyclohexanecarboxylic acid Chemical compound OC(=O)C1CCCCC1 NZNMSOFKMUBTKW-UHFFFAOYSA-N 0.000 description 25
• 239000012074 organic phase Substances 0.000 description 25
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 24
• 239000012071 phase Substances 0.000 description 24
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 description 22
• 101000610640 Homo sapiens U4/U6 small nuclear ribonucleoprotein Prp3 Proteins 0.000 description 22
• 101001110823 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-A Proteins 0.000 description 22
• 101000712176 Saccharomyces cerevisiae (strain ATCC 204508 / S288c) 60S ribosomal protein L6-B Proteins 0.000 description 22
• 102100040374 U4/U6 small nuclear ribonucleoprotein Prp3 Human genes 0.000 description 22
• KXKVLQRXCPHEJC-UHFFFAOYSA-N methyl acetate Chemical compound COC(C)=O KXKVLQRXCPHEJC-UHFFFAOYSA-N 0.000 description 22
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 21
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 18
• 125000004494 ethyl ester group Chemical group 0.000 description 17
• 229960002449 glycine Drugs 0.000 description 17
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
• 238000010992 reflux Methods 0.000 description 16
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 15
• 239000004471 Glycine Substances 0.000 description 15
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 15
• DCKVNWZUADLDEH-UHFFFAOYSA-N sec-butyl acetate Chemical compound CCC(C)OC(C)=O DCKVNWZUADLDEH-UHFFFAOYSA-N 0.000 description 15
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 14
• 239000012043 crude product Substances 0.000 description 14
• 239000003480 eluent Substances 0.000 description 14
• IHTYTYHXCRAMAV-UHFFFAOYSA-N acetic acid;dihydrochloride Chemical compound Cl.Cl.CC(O)=O IHTYTYHXCRAMAV-UHFFFAOYSA-N 0.000 description 13
• 239000002585 base Substances 0.000 description 13
• 238000009835 boiling Methods 0.000 description 13
• 229910000027 potassium carbonate Inorganic materials 0.000 description 13
• 239000000725 suspension Substances 0.000 description 13
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 13
• WMFOQBRAJBCJND-UHFFFAOYSA-M Lithium hydroxide Chemical compound [Li+].[OH-] WMFOQBRAJBCJND-UHFFFAOYSA-M 0.000 description 12
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• QJDVHHUSFFIXCO-UHFFFAOYSA-N methyl 2-[(1-benzylpiperidin-4-yl)-[(2-methylpropan-2-yl)oxycarbonyl]amino]acetate;dihydrochloride Chemical compound Cl.Cl.C1CC(N(CC(=O)OC)C(=O)OC(C)(C)C)CCN1CC1=CC=CC=C1 QJDVHHUSFFIXCO-UHFFFAOYSA-N 0.000 description 1
• WQTZUOFFUPMIPZ-UHFFFAOYSA-N methyl 2-[(1-benzylpiperidin-4-yl)-methylamino]acetate;dihydrochloride Chemical compound Cl.Cl.C1CC(N(C)CC(=O)OC)CCN1CC1=CC=CC=C1 WQTZUOFFUPMIPZ-UHFFFAOYSA-N 0.000 description 1
• SAQHLMVVQFAKRH-QRPNPIFTSA-N methyl 2-[1-[(2s)-2-aminopropanoyl]piperidin-4-yl]oxyacetate;2,2,2-trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F.COC(=O)COC1CCN(C(=O)[C@H](C)N)CC1 SAQHLMVVQFAKRH-QRPNPIFTSA-N 0.000 description 1
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