IE920928A1 - Benzofuran derivatives - Google Patents

Info

Publication number

IE920928A1

IE920928A1 IE920928A IE920928A IE920928A1 IE 920928 A1 IE920928 A1 IE 920928A1 IE 920928 A IE920928 A IE 920928A IE 920928 A IE920928 A IE 920928A IE 920928 A1 IE920928 A1 IE 920928A1

Authority

IE

Ireland

Prior art keywords

group

hydrogen atom

bromo

phenyl

chloro

Prior art date

1991-03-25

Links

• Espacenet
• Global Dossier
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• 150000001907 coumarones Chemical class 0.000 title description 2
• 150000001875 compounds Chemical class 0.000 claims abstract description 190
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims abstract description 90
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 73
• -1 amino, guanidino, imidazolyl Chemical group 0.000 claims abstract description 57
• 150000003839 salts Chemical class 0.000 claims abstract description 49
• 150000002148 esters Chemical class 0.000 claims abstract description 40
• 239000012453 solvate Substances 0.000 claims abstract description 29
• 125000005843 halogen group Chemical group 0.000 claims abstract description 27
• 238000011282 treatment Methods 0.000 claims abstract description 26
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 18
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims abstract description 15
• 125000003831 tetrazolyl group Chemical group 0.000 claims abstract description 14
• 125000000623 heterocyclic group Chemical group 0.000 claims abstract description 10
• 238000011321 prophylaxis Methods 0.000 claims abstract description 7
• 206010020772 Hypertension Diseases 0.000 claims abstract description 6
• 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 6
• 125000004430 oxygen atom Chemical group O* 0.000 claims abstract description 6
• 125000003368 amide group Chemical group 0.000 claims abstract description 5
• 125000004464 hydroxyphenyl group Chemical group 0.000 claims abstract description 5
• 125000001041 indolyl group Chemical group 0.000 claims abstract description 5
• PXQLVRUNWNTZOS-UHFFFAOYSA-N sulfanyl Chemical class [SH] PXQLVRUNWNTZOS-UHFFFAOYSA-N 0.000 claims abstract description 5
• 208000010877 cognitive disease Diseases 0.000 claims abstract description 3
• 125000006700 (C1-C6) alkylthio group Chemical group 0.000 claims abstract 2
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 99
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 97
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 86
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 68
• 239000000203 mixture Substances 0.000 claims description 47
• 238000000034 method Methods 0.000 claims description 34
• NTNZTEQNFHNYBC-UHFFFAOYSA-N ethyl 2-aminoacetate Chemical compound CCOC(=O)CN NTNZTEQNFHNYBC-UHFFFAOYSA-N 0.000 claims description 31
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 28
• 125000000217 alkyl group Chemical group 0.000 claims description 23
• DHMQDGOQFOQNFH-UHFFFAOYSA-N Glycine Chemical compound NCC(O)=O DHMQDGOQFOQNFH-UHFFFAOYSA-N 0.000 claims description 22
• 125000004494 ethyl ester group Chemical group 0.000 claims description 19
• 102000005862 Angiotensin II Human genes 0.000 claims description 17
• 101800000733 Angiotensin-2 Proteins 0.000 claims description 17
• CZGUSIXMZVURDU-JZXHSEFVSA-N Ile(5)-angiotensin II 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-])=O)NC(=O)[C@@H](NC(=O)[C@H](CCCNC(N)=[NH2+])NC(=O)[C@@H]([NH3+])CC([O-])=O)C(C)C)C1=CC=C(O)C=C1 CZGUSIXMZVURDU-JZXHSEFVSA-N 0.000 claims description 17
• 229950006323 angiotensin ii Drugs 0.000 claims description 17
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 16
• RAHZWNYVWXNFOC-UHFFFAOYSA-N Sulphur dioxide Chemical group O=S=O RAHZWNYVWXNFOC-UHFFFAOYSA-N 0.000 claims description 15
• 230000008569 process Effects 0.000 claims description 15
• 239000002253 acid Substances 0.000 claims description 14
• 125000006239 protecting group Chemical group 0.000 claims description 12
• 238000002360 preparation method Methods 0.000 claims description 10
• IANQTJSKSUMEQM-UHFFFAOYSA-N 1-benzofuran Chemical group C1=CC=C2OC=CC2=C1 IANQTJSKSUMEQM-UHFFFAOYSA-N 0.000 claims description 9
• 239000003814 drug Substances 0.000 claims description 7
• KQSSATDQUYCRGS-UHFFFAOYSA-N methyl glycinate Chemical compound COC(=O)CN KQSSATDQUYCRGS-UHFFFAOYSA-N 0.000 claims description 7
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 6
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 6
• 125000000499 benzofuranyl group Chemical group O1C(=CC2=C1C=CC=C2)* 0.000 claims description 6
• 230000000694 effects Effects 0.000 claims description 6
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 6
• 239000008194 pharmaceutical composition Substances 0.000 claims description 6
• 230000004913 activation Effects 0.000 claims description 5
• 125000002560 nitrile group Chemical group 0.000 claims description 5
• 230000036454 renin-angiotensin system Effects 0.000 claims description 5
• 206010019280 Heart failures Diseases 0.000 claims description 4
• 208000001647 Renal Insufficiency Diseases 0.000 claims description 4
• 229960003767 alanine Drugs 0.000 claims description 4
• 125000003342 alkenyl group Chemical group 0.000 claims description 4
• 229910052801 chlorine Inorganic materials 0.000 claims description 4
• ZPUCINDJVBIVPJ-LJISPDSOSA-N cocaine Chemical compound O([C@H]1C[C@@H]2CC[C@@H](N2C)[C@H]1C(=O)OC)C(=O)C1=CC=CC=C1 ZPUCINDJVBIVPJ-LJISPDSOSA-N 0.000 claims description 4
• PXBRQCKWGAHEHS-UHFFFAOYSA-N dichlorodifluoromethane Chemical compound FC(F)(Cl)Cl PXBRQCKWGAHEHS-UHFFFAOYSA-N 0.000 claims description 4
• 125000000336 imidazol-5-yl group Chemical group [H]N1C([H])=NC([H])=C1[*] 0.000 claims description 4
• 201000006370 kidney failure Diseases 0.000 claims description 4
• QQONPFPTGQHPMA-UHFFFAOYSA-N propylene Natural products CC=C QQONPFPTGQHPMA-UHFFFAOYSA-N 0.000 claims description 4
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 3
• 125000003545 alkoxy group Chemical group 0.000 claims description 3
• 125000003277 amino group Chemical group 0.000 claims description 3
• 150000001540 azides Chemical class 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
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 3
• 229960000310 isoleucine Drugs 0.000 claims description 3
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
• 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 3
• 239000000546 pharmaceutical excipient Substances 0.000 claims description 3
• 229960005190 phenylalanine Drugs 0.000 claims description 3
• 125000004805 propylene group Chemical group [H]C([H])([H])C([H])([*:1])C([H])([H])[*:2] 0.000 claims description 3
• WJKHJLXJJJATHN-UHFFFAOYSA-N triflic anhydride Chemical compound FC(F)(F)S(=O)(=O)OS(=O)(=O)C(F)(F)F WJKHJLXJJJATHN-UHFFFAOYSA-N 0.000 claims description 3
• 230000002792 vascular Effects 0.000 claims description 3
• HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims description 2
• 208000024827 Alzheimer disease Diseases 0.000 claims description 2
• 208000019901 Anxiety disease Diseases 0.000 claims description 2
• 201000001320 Atherosclerosis Diseases 0.000 claims description 2
• 208000012904 Bartter disease Diseases 0.000 claims description 2
• 208000010062 Bartter syndrome Diseases 0.000 claims description 2
• 206010007556 Cardiac failure acute Diseases 0.000 claims description 2
• 206010007558 Cardiac failure chronic Diseases 0.000 claims description 2
• 206010007559 Cardiac failure congestive Diseases 0.000 claims description 2
• 206010058842 Cerebrovascular insufficiency Diseases 0.000 claims description 2
• 206010012289 Dementia Diseases 0.000 claims description 2
• 208000007342 Diabetic Nephropathies Diseases 0.000 claims description 2
• 206010012689 Diabetic retinopathy Diseases 0.000 claims description 2
• 206010018364 Glomerulonephritis Diseases 0.000 claims description 2
• 206010020571 Hyperaldosteronism Diseases 0.000 claims description 2
• 206010039710 Scleroderma Diseases 0.000 claims description 2
• 230000001154 acute effect Effects 0.000 claims description 2
• 125000004414 alkyl thio group Chemical group 0.000 claims description 2
• 201000002064 aortic valve insufficiency Diseases 0.000 claims description 2
• 230000036523 atherogenesis Effects 0.000 claims description 2
• 208000026106 cerebrovascular disease Diseases 0.000 claims description 2
• 229960003920 cocaine Drugs 0.000 claims description 2
• 125000004186 cyclopropylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C1([H])[H] 0.000 claims description 2
• 208000033679 diabetic kidney disease Diseases 0.000 claims description 2
• 229940079593 drug Drugs 0.000 claims description 2
• BEBCJVAWIBVWNZ-UHFFFAOYSA-N glycinamide Chemical compound NCC(N)=O BEBCJVAWIBVWNZ-UHFFFAOYSA-N 0.000 claims description 2
• 125000002883 imidazolyl group Chemical group 0.000 claims description 2
• 230000006872 improvement Effects 0.000 claims description 2
• 201000009395 primary hyperaldosteronism Diseases 0.000 claims description 2
• 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 2
• 201000001474 proteinuria Diseases 0.000 claims description 2
• 201000000980 schizophrenia Diseases 0.000 claims description 2
• 208000011580 syndromic disease Diseases 0.000 claims description 2
• 238000002560 therapeutic procedure Methods 0.000 claims description 2
• CYRMSUTZVYGINF-UHFFFAOYSA-N trichlorofluoromethane Chemical compound FC(Cl)(Cl)Cl CYRMSUTZVYGINF-UHFFFAOYSA-N 0.000 claims description 2
• GRGCWBWNLSTIEN-UHFFFAOYSA-N trifluoromethanesulfonyl chloride Chemical compound FC(F)(F)S(Cl)(=O)=O GRGCWBWNLSTIEN-UHFFFAOYSA-N 0.000 claims description 2
• WUZHRBRUBCBRLJ-UHFFFAOYSA-N 2-[3-bromo-5-[[2-butyl-5-(carboxymethylcarbamoyl)-4-chloroimidazol-1-yl]methyl]-1-benzofuran-2-yl]benzoic acid Chemical compound CCCCC1=NC(Cl)=C(C(=O)NCC(O)=O)N1CC1=CC=C(OC(=C2Br)C=3C(=CC=CC=3)C(O)=O)C2=C1 WUZHRBRUBCBRLJ-UHFFFAOYSA-N 0.000 claims 1
• KQASWVPNJUFXOK-UHFFFAOYSA-N 2-[[3-[[3-bromo-2-[2-(2h-tetrazol-5-yl)phenyl]-1-benzofuran-5-yl]methyl]-2-ethyl-5-methylimidazole-4-carbonyl]amino]acetic acid Chemical compound CCC1=NC(C)=C(C(=O)NCC(O)=O)N1CC1=CC=C(OC(=C2Br)C=3C(=CC=CC=3)C3=NNN=N3)C2=C1 KQASWVPNJUFXOK-UHFFFAOYSA-N 0.000 claims 1
• JQYWBRQSQKFDIN-UHFFFAOYSA-N 2-[[3-[[3-bromo-2-[2-(2h-tetrazol-5-yl)phenyl]-1-benzofuran-5-yl]methyl]-5-chloro-2-ethylimidazole-4-carbonyl]amino]acetic acid Chemical compound CCC1=NC(Cl)=C(C(=O)NCC(O)=O)N1CC1=CC=C(OC(=C2Br)C=3C(=CC=CC=3)C3=NNN=N3)C2=C1 JQYWBRQSQKFDIN-UHFFFAOYSA-N 0.000 claims 1
• 208000015114 central nervous system disease Diseases 0.000 claims 1
• 125000001309 chloro group Chemical group Cl* 0.000 claims 1
• DBKFVDYBLKJGIZ-UHFFFAOYSA-N methyl 2-[[3-[[3-bromo-2-[2-(2h-tetrazol-5-yl)phenyl]-1-benzofuran-5-yl]methyl]-2-butyl-5-chloroimidazole-4-carbonyl]amino]acetate Chemical compound CCCCC1=NC(Cl)=C(C(=O)NCC(=O)OC)N1CC1=CC=C(OC(=C2Br)C=3C(=CC=CC=3)C3=NNN=N3)C2=C1 DBKFVDYBLKJGIZ-UHFFFAOYSA-N 0.000 claims 1
• 208000010125 myocardial infarction Diseases 0.000 claims 1
• 230000002093 peripheral effect Effects 0.000 claims 1
• SNOOUWRIMMFWNE-UHFFFAOYSA-M sodium;6-[(3,4,5-trimethoxybenzoyl)amino]hexanoate Chemical compound [Na+].COC1=CC(C(=O)NCCCCCC([O-])=O)=CC(OC)=C1OC SNOOUWRIMMFWNE-UHFFFAOYSA-M 0.000 claims 1
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 abstract description 5
• 125000000882 C2-C6 alkenyl group Chemical group 0.000 abstract description 4
• 201000010099 disease Diseases 0.000 abstract description 4
• 239000000543 intermediate Substances 0.000 description 120
• 239000000243 solution Substances 0.000 description 80
• RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 74
• HIXDQWDOVZUNNA-UHFFFAOYSA-N 2-(3,4-dimethoxyphenyl)-5-hydroxy-7-methoxychromen-4-one Chemical compound C=1C(OC)=CC(O)=C(C(C=2)=O)C=1OC=2C1=CC=C(OC)C(OC)=C1 HIXDQWDOVZUNNA-UHFFFAOYSA-N 0.000 description 72
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 66
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 54
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 54
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 46
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 38
• 235000019441 ethanol Nutrition 0.000 description 36
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical group N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 30
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 30
• 239000007787 solid Substances 0.000 description 29
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 27
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 26
• 239000002904 solvent Substances 0.000 description 25
• 238000006243 chemical reaction Methods 0.000 description 20
• 239000000047 product Substances 0.000 description 20
• 229910052757 nitrogen Inorganic materials 0.000 description 17
• 239000000843 powder Substances 0.000 description 16
• 239000000284 extract Substances 0.000 description 15
• 239000002585 base Substances 0.000 description 14
• 239000006260 foam Substances 0.000 description 14
• 238000010992 reflux Methods 0.000 description 13
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 12
• 239000004480 active ingredient Substances 0.000 description 12
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 10
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 10
• 239000000725 suspension Substances 0.000 description 10
• TXTWXQXDMWILOF-UHFFFAOYSA-N (2-ethoxy-2-oxoethyl)azanium;chloride Chemical compound [Cl-].CCOC(=O)C[NH3+] TXTWXQXDMWILOF-UHFFFAOYSA-N 0.000 description 9
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 8
• 238000003556 assay Methods 0.000 description 8
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Chemical compound BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 8
• 238000003818 flash chromatography Methods 0.000 description 8
• 239000010410 layer Substances 0.000 description 8
• HQKMJHAJHXVSDF-UHFFFAOYSA-L magnesium stearate Chemical compound [Mg+2].CCCCCCCCCCCCCCCCCC([O-])=O.CCCCCCCCCCCCCCCCCC([O-])=O HQKMJHAJHXVSDF-UHFFFAOYSA-L 0.000 description 8
• 239000003826 tablet Substances 0.000 description 8
• VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 8
• OZAIFHULBGXAKX-UHFFFAOYSA-N 2-(2-cyanopropan-2-yldiazenyl)-2-methylpropanenitrile Chemical compound N#CC(C)(C)N=NC(C)(C)C#N OZAIFHULBGXAKX-UHFFFAOYSA-N 0.000 description 7
• HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 7
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 7
• 239000003921 oil Substances 0.000 description 7
• 235000019198 oils Nutrition 0.000 description 7
• 125000001424 substituent group Chemical group 0.000 description 7
• BKOOMYPCSUNDGP-UHFFFAOYSA-N 2-methylbut-2-ene Chemical compound CC=C(C)C BKOOMYPCSUNDGP-UHFFFAOYSA-N 0.000 description 6
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 6
• GUBGYTABKSRVRQ-QKKXKWKRSA-N Lactose Natural products OC[C@H]1O[C@@H](O[C@H]2[C@H](O)[C@@H](O)C(O)O[C@@H]2CO)[C@H](O)[C@@H](O)[C@H]1O GUBGYTABKSRVRQ-QKKXKWKRSA-N 0.000 description 6
• PXIPVTKHYLBLMZ-UHFFFAOYSA-N Sodium azide Chemical compound [Na+].[N-]=[N+]=[N-] PXIPVTKHYLBLMZ-UHFFFAOYSA-N 0.000 description 6
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 6
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 6
• 239000005557 antagonist Substances 0.000 description 6
• 239000008346 aqueous phase Substances 0.000 description 6
• 239000012267 brine Substances 0.000 description 6
• 229910052794 bromium Inorganic materials 0.000 description 6
• 238000010511 deprotection reaction Methods 0.000 description 6
• 239000008101 lactose Substances 0.000 description 6
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
• 239000011541 reaction mixture Substances 0.000 description 6
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 6
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 5
• 239000004471 Glycine Substances 0.000 description 5
• 239000012074 organic phase Substances 0.000 description 5
• 229910000027 potassium carbonate Inorganic materials 0.000 description 5
• 238000000746 purification Methods 0.000 description 5
• 230000004044 response Effects 0.000 description 5
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
• VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 4
• 241000124008 Mammalia Species 0.000 description 4
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 4
• KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 4
• CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 4
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
• 150000001408 amides Chemical class 0.000 description 4
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 4
• PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 4
• 239000003153 chemical reaction reagent Substances 0.000 description 4
• 239000000460 chlorine Substances 0.000 description 4
• 238000004587 chromatography analysis Methods 0.000 description 4
• 238000004440 column chromatography Methods 0.000 description 4
• 230000001186 cumulative effect Effects 0.000 description 4
• FAMRKDQNMBBFBR-BQYQJAHWSA-N diethyl azodicarboxylate Substances CCOC(=O)\N=N\C(=O)OCC FAMRKDQNMBBFBR-BQYQJAHWSA-N 0.000 description 4
• 238000001914 filtration Methods 0.000 description 4
• 230000008570 general process Effects 0.000 description 4
• 235000019359 magnesium stearate Nutrition 0.000 description 4
• 239000003208 petroleum Substances 0.000 description 4
• 229940080313 sodium starch Drugs 0.000 description 4
• 229940124597 therapeutic agent Drugs 0.000 description 4
• 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 4
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 3
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 3
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