SK285991B6 - Pyrazolopyrimidinóny, spôsob a medziprodukty na ich výrobu, ich použitie a farmaceutické a veterinárne kompozície na ich báze - Google Patents

Info

Publication number

SK285991B6

SK285991B6 SK1446-99A SK144699A SK285991B6 SK 285991 B6 SK285991 B6 SK 285991B6 SK 144699 A SK144699 A SK 144699A SK 285991 B6 SK285991 B6 SK 285991B6

Authority

SK

Slovakia

Prior art keywords

preparation

pyrimidin

methyl

title compound

pyrazolo

Prior art date

1997-04-25

Links

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• Global Dossier
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• 238000000034 method Methods 0.000 title claims abstract description 232
• DOTPSQVYOBAWPQ-UHFFFAOYSA-N pyrazolo[4,3-d]pyrimidin-3-one Chemical class N1=CN=C2C(=O)N=NC2=C1 DOTPSQVYOBAWPQ-UHFFFAOYSA-N 0.000 title claims abstract description 31
• 239000000543 intermediate Substances 0.000 title claims abstract description 14
• 230000008569 process Effects 0.000 title claims abstract description 7
• 239000000203 mixture Substances 0.000 title claims description 66
• 238000002360 preparation method Methods 0.000 claims abstract description 488
• 150000001875 compounds Chemical class 0.000 claims abstract description 426
• 239000003814 drug Substances 0.000 claims abstract description 14
• 238000004519 manufacturing process Methods 0.000 claims abstract description 9
• 241001465754 Metazoa Species 0.000 claims abstract description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims abstract description 6
• 208000010228 Erectile Dysfunction Diseases 0.000 claims abstract description 5
• 206010057671 Female sexual dysfunction Diseases 0.000 claims abstract description 5
• 229940123333 Phosphodiesterase 5 inhibitor Drugs 0.000 claims abstract description 5
• 201000001881 impotence Diseases 0.000 claims abstract description 5
• 239000002590 phosphodiesterase V inhibitor Substances 0.000 claims abstract description 5
• -1 1-oxidopyridinyl Chemical group 0.000 claims description 260
• 230000002829 reductive effect Effects 0.000 claims description 79
• 229910052739 hydrogen Inorganic materials 0.000 claims description 76
• 150000003839 salts Chemical class 0.000 claims description 53
• 239000012453 solvate Substances 0.000 claims description 28
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 21
• 229910052757 nitrogen Inorganic materials 0.000 claims description 21
• 125000000217 alkyl group Chemical group 0.000 claims description 20
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 19
• ZOOGRGPOEVQQDX-UUOKFMHZSA-N 3',5'-cyclic GMP Chemical compound C([C@H]1O2)OP(O)(=O)O[C@H]1[C@@H](O)[C@@H]2N1C(N=C(NC2=O)N)=C2N=C1 ZOOGRGPOEVQQDX-UUOKFMHZSA-N 0.000 claims description 15
• XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 15
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 14
• 239000000460 chlorine Substances 0.000 claims description 12
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 11
• 125000001424 substituent group Chemical group 0.000 claims description 11
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 10
• 125000002757 morpholinyl group Chemical group 0.000 claims description 10
• 125000002206 pyridazin-3-yl group Chemical group [H]C1=C([H])C([H])=C(*)N=N1 0.000 claims description 10
• 125000001425 triazolyl group Chemical group 0.000 claims description 10
• 229910052736 halogen Inorganic materials 0.000 claims description 9
• ZYHQGITXIJDDKC-UHFFFAOYSA-N 2-[2-(2-aminophenyl)ethyl]aniline Chemical group NC1=CC=CC=C1CCC1=CC=CC=C1N ZYHQGITXIJDDKC-UHFFFAOYSA-N 0.000 claims description 8
• 206010004446 Benign prostatic hyperplasia Diseases 0.000 claims description 8
• 208000004403 Prostatic Hyperplasia Diseases 0.000 claims description 8
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 8
• UUEVFMOUBSLVJW-UHFFFAOYSA-N oxo-[[1-[2-[2-[2-[4-(oxoazaniumylmethylidene)pyridin-1-yl]ethoxy]ethoxy]ethyl]pyridin-4-ylidene]methyl]azanium;dibromide Chemical compound [Br-].[Br-].C1=CC(=C[NH+]=O)C=CN1CCOCCOCCN1C=CC(=C[NH+]=O)C=C1 UUEVFMOUBSLVJW-UHFFFAOYSA-N 0.000 claims description 8
• 125000004307 pyrazin-2-yl group Chemical group [H]C1=C([H])N=C(*)C([H])=N1 0.000 claims description 8
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 7
• 125000003545 alkoxy group Chemical group 0.000 claims description 7
• 230000015572 biosynthetic process Effects 0.000 claims description 7
• 150000002367 halogens Chemical class 0.000 claims description 7
• 125000002883 imidazolyl group Chemical group 0.000 claims description 7
• 125000004076 pyridyl group Chemical group 0.000 claims description 7
• 229910052799 carbon Inorganic materials 0.000 claims description 6
• 229910052801 chlorine Inorganic materials 0.000 claims description 6
• 238000009109 curative therapy Methods 0.000 claims description 6
• 125000000623 heterocyclic group Chemical group 0.000 claims description 6
• 238000011321 prophylaxis Methods 0.000 claims description 6
• 125000003373 pyrazinyl group Chemical group 0.000 claims description 6
• 125000002098 pyridazinyl group Chemical group 0.000 claims description 6
• 125000000246 pyrimidin-2-yl group Chemical group [H]C1=NC(*)=NC([H])=C1[H] 0.000 claims description 6
• 125000000714 pyrimidinyl group Chemical group 0.000 claims description 6
• UKJLNMAFNRKWGR-UHFFFAOYSA-N cyclohexatrienamine Chemical group NC1=CC=C=C[CH]1 UKJLNMAFNRKWGR-UHFFFAOYSA-N 0.000 claims description 5
• 208000035475 disorder Diseases 0.000 claims description 5
• 239000001257 hydrogen Substances 0.000 claims description 5
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 5
• 125000001715 oxadiazolyl group Chemical group 0.000 claims description 5
• 125000000636 p-nitrophenyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1*)[N+]([O-])=O 0.000 claims description 5
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 5
• 125000004528 pyrimidin-5-yl group Chemical group N1=CN=CC(=C1)* 0.000 claims description 5
• 125000000335 thiazolyl group Chemical group 0.000 claims description 5
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
• 206010002383 Angina Pectoris Diseases 0.000 claims description 4
• 208000005171 Dysmenorrhea Diseases 0.000 claims description 4
• 206010013935 Dysmenorrhoea Diseases 0.000 claims description 4
• 206010019280 Heart failures Diseases 0.000 claims description 4
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 4
• 206010020772 Hypertension Diseases 0.000 claims description 4
• 206010021639 Incontinence Diseases 0.000 claims description 4
• 208000006011 Stroke Diseases 0.000 claims description 4
• 239000003085 diluting agent Substances 0.000 claims description 4
• 230000008991 intestinal motility Effects 0.000 claims description 4
• 208000002815 pulmonary hypertension Diseases 0.000 claims description 4
• 125000004940 pyridazin-4-yl group Chemical group N1=NC=C(C=C1)* 0.000 claims description 4
• 125000004527 pyrimidin-4-yl group Chemical group N1=CN=C(C=C1)* 0.000 claims description 4
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 4
• 125000003626 1,2,4-triazol-1-yl group Chemical group [*]N1N=C([H])N=C1[H] 0.000 claims description 3
• 125000004800 4-bromophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Br 0.000 claims description 3
• 125000004195 4-methylpiperazin-1-yl group Chemical group [H]C([H])([H])N1C([H])([H])C([H])([H])N(*)C([H])([H])C1([H])[H] 0.000 claims description 3
• OXDOBIWISZSZOR-UHFFFAOYSA-N C(C)N1CCN(CC1)S(=O)(=O)C=1C=CC(=C(C1)C=1N(C(C=2C(N1)=C(N(N2)C2=NC=CN=C2)CCC)=O)C)OCCC Chemical compound C(C)N1CCN(CC1)S(=O)(=O)C=1C=CC(=C(C1)C=1N(C(C=2C(N1)=C(N(N2)C2=NC=CN=C2)CCC)=O)C)OCCC OXDOBIWISZSZOR-UHFFFAOYSA-N 0.000 claims description 3
• JHMSBKZJUOXPGR-UHFFFAOYSA-N CN1C(=NC=C1)N1N=C(C=2N=C(N(C(C21)=O)C)C2=C(C=CC(=C2)S(=O)(=O)N2CCN(CC2)C)OCCC)CCC Chemical compound CN1C(=NC=C1)N1N=C(C=2N=C(N(C(C21)=O)C)C2=C(C=CC(=C2)S(=O)(=O)N2CCN(CC2)C)OCCC)CCC JHMSBKZJUOXPGR-UHFFFAOYSA-N 0.000 claims description 3
• 208000010412 Glaucoma Diseases 0.000 claims description 3
• 208000031481 Pathologic Constriction Diseases 0.000 claims description 3
• 208000006399 Premature Obstetric Labor Diseases 0.000 claims description 3
• 206010036600 Premature labour Diseases 0.000 claims description 3
• 201000009961 allergic asthma Diseases 0.000 claims description 3
• 208000006673 asthma Diseases 0.000 claims description 3
• 239000008280 blood Substances 0.000 claims description 3
• 210000004369 blood Anatomy 0.000 claims description 3
• 206010006451 bronchitis Diseases 0.000 claims description 3
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 3
• 208000023819 chronic asthma Diseases 0.000 claims description 3
• 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 3
• 125000004850 cyclobutylmethyl group Chemical group C1(CCC1)C* 0.000 claims description 3
• 201000010099 disease Diseases 0.000 claims description 3
• 125000003854 p-chlorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1Cl 0.000 claims description 3
• 125000003386 piperidinyl group Chemical group 0.000 claims description 3
• 208000026440 premature labor Diseases 0.000 claims description 3
• 208000037804 stenosis Diseases 0.000 claims description 3
• 230000036262 stenosis Effects 0.000 claims description 3
• 125000005913 (C3-C6) cycloalkyl group Chemical group 0.000 claims description 2
• 125000001766 1,2,4-oxadiazol-3-yl group Chemical group [H]C1=NC(*)=NO1 0.000 claims description 2
• BDRKFVMARPGNIY-UHFFFAOYSA-N OCCN1CCN(CC1)S(=O)(=O)C=1C=CC(=C(C1)C=1N(C(C=2C(N1)=C(N(N2)C2=NC=CC=C2)CCC)=O)C)OCCC Chemical compound OCCN1CCN(CC1)S(=O)(=O)C=1C=CC(=C(C1)C=1N(C(C=2C(N1)=C(N(N2)C2=NC=CC=C2)CCC)=O)C)OCCC BDRKFVMARPGNIY-UHFFFAOYSA-N 0.000 claims description 2
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 2
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims 4
• 125000001607 1,2,3-triazol-1-yl group Chemical group [*]N1N=NC([H])=C1[H] 0.000 claims 2
• 206010039085 Rhinitis allergic Diseases 0.000 claims 2
• 201000010105 allergic rhinitis Diseases 0.000 claims 2
• 125000005843 halogen group Chemical group 0.000 claims 2
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims 2
• 125000004353 pyrazol-1-yl group Chemical group [H]C1=NN(*)C([H])=C1[H] 0.000 claims 2
• 230000002792 vascular Effects 0.000 claims 2
• NCNHKGZVJKQTMB-UHFFFAOYSA-N 2-methyl-4h-pyrazolo[4,3-d]pyrimidin-7-one Chemical compound N1=CNC(=O)C2=NN(C)C=C21 NCNHKGZVJKQTMB-UHFFFAOYSA-N 0.000 claims 1
• 201000001880 Sexual dysfunction Diseases 0.000 claims 1
• 208000019622 heart disease Diseases 0.000 claims 1
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims 1
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims 1
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims 1
• 231100000872 sexual dysfunction Toxicity 0.000 claims 1
• 102000004861 Phosphoric Diester Hydrolases Human genes 0.000 abstract description 17
• 108090001050 Phosphoric Diester Hydrolases Proteins 0.000 abstract description 17
• 229940124639 Selective inhibitor Drugs 0.000 abstract description 3
• 239000007787 solid Substances 0.000 description 172
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 147
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 129
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 107
• 239000000243 solution Substances 0.000 description 105
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 93
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 80
• 239000006260 foam Substances 0.000 description 72
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 59
• PVOAHINGSUIXLS-UHFFFAOYSA-N 1-Methylpiperazine Chemical compound CN1CCNCC1 PVOAHINGSUIXLS-UHFFFAOYSA-N 0.000 description 53
• 239000011541 reaction mixture Substances 0.000 description 41
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 38
• HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 37
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 34
• 238000010898 silica gel chromatography Methods 0.000 description 31
• WGCYRFWNGRMRJA-UHFFFAOYSA-N 1-ethylpiperazine Chemical compound CCN1CCNCC1 WGCYRFWNGRMRJA-UHFFFAOYSA-N 0.000 description 30
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 27
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
• 238000010992 reflux Methods 0.000 description 26
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 22
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
• ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 20
• 238000006243 chemical reaction Methods 0.000 description 19
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 19
• 235000019341 magnesium sulphate Nutrition 0.000 description 19
• IJGRMHOSHXDMSA-UHFFFAOYSA-N nitrogen Substances N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 19
• 239000002904 solvent Substances 0.000 description 19
• 239000000725 suspension Substances 0.000 description 19
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 18
• 239000003480 eluent Substances 0.000 description 18
• 239000003921 oil Substances 0.000 description 18
• 235000019198 oils Nutrition 0.000 description 18
• WFCSWCVEJLETKA-UHFFFAOYSA-N 2-piperazin-1-ylethanol Chemical compound OCCN1CCNCC1 WFCSWCVEJLETKA-UHFFFAOYSA-N 0.000 description 17
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 17
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 16
• 239000012458 free base Substances 0.000 description 16
• 239000000284 extract Substances 0.000 description 15
• 239000000843 powder Substances 0.000 description 15
• 239000006071 cream Substances 0.000 description 14
• FYSNRJHAOHDILO-UHFFFAOYSA-N thionyl chloride Chemical compound ClS(Cl)=O FYSNRJHAOHDILO-UHFFFAOYSA-N 0.000 description 14
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 13
• 238000001816 cooling Methods 0.000 description 13
• 229910052938 sodium sulfate Inorganic materials 0.000 description 13
• 235000011152 sodium sulphate Nutrition 0.000 description 13
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 12
• 239000002253 acid Substances 0.000 description 12
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 12
• 239000012074 organic phase Substances 0.000 description 12
• BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 12
• 239000008346 aqueous phase Substances 0.000 description 11
• 239000002585 base Substances 0.000 description 11
• ZOOGRGPOEVQQDX-UHFFFAOYSA-N cyclic GMP Natural products O1C2COP(O)(=O)OC2C(O)C1N1C=NC2=C1NC(N)=NC2=O ZOOGRGPOEVQQDX-UHFFFAOYSA-N 0.000 description 11
• 239000012258 stirred mixture Substances 0.000 description 11
• YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 10
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• 238000002425 crystallisation Methods 0.000 description 10
• 230000008025 crystallization Effects 0.000 description 10
• 239000000706 filtrate Substances 0.000 description 10
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 10
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• 239000002244 precipitate Substances 0.000 description 9
• 239000011734 sodium Substances 0.000 description 9
• UIIMBOGNXHQVGW-UHFFFAOYSA-M sodium bicarbonate Substances [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 9
• 238000003756 stirring Methods 0.000 description 9
• NJWIMFZLESWFIM-UHFFFAOYSA-N 2-(chloromethyl)pyridine Chemical compound ClCC1=CC=CC=N1 NJWIMFZLESWFIM-UHFFFAOYSA-N 0.000 description 8
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 description 8
• 102100024085 Alpha-aminoadipic semialdehyde dehydrogenase Human genes 0.000 description 8
• OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 8
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• 238000005804 alkylation reaction Methods 0.000 description 8
• QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 8
• 239000012043 crude product Substances 0.000 description 8
• 238000001914 filtration Methods 0.000 description 8
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 8
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• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 7
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• IBYHHJPAARCAIE-UHFFFAOYSA-N 1-bromo-2-chloroethane Chemical compound ClCCBr IBYHHJPAARCAIE-UHFFFAOYSA-N 0.000 description 6
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• 230000029936 alkylation Effects 0.000 description 6
• 239000003153 chemical reaction reagent Substances 0.000 description 6
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 6
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• 238000003786 synthesis reaction Methods 0.000 description 6
• 238000011282 treatment Methods 0.000 description 6
• JIAARYAFYJHUJI-UHFFFAOYSA-L zinc dichloride Chemical compound [Cl-].[Cl-].[Zn+2] JIAARYAFYJHUJI-UHFFFAOYSA-L 0.000 description 6
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• 208000018262 Peripheral vascular disease Diseases 0.000 description 5
• ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 5
• 239000007864 aqueous solution Substances 0.000 description 5
• 238000004440 column chromatography Methods 0.000 description 5
• GLUUGHFHXGJENI-UHFFFAOYSA-N diethylenediamine Natural products C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 5
• 239000012299 nitrogen atmosphere Substances 0.000 description 5
• 239000011591 potassium Substances 0.000 description 5
• 238000007363 ring formation reaction Methods 0.000 description 5
• 235000017557 sodium bicarbonate Nutrition 0.000 description 5
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 5
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