SK285958B6 - Inhibítory retrovírusovej proteázy na báze bis-aminokyselinahydroxyetylaminosulfónamidu - Google Patents

Info

Publication number

SK285958B6

SK285958B6 SK5091-2006A SK50912006A SK285958B6 SK 285958 B6 SK285958 B6 SK 285958B6 SK 50912006 A SK50912006 A SK 50912006A SK 285958 B6 SK285958 B6 SK 285958B6

Authority

SK

Slovakia

Prior art keywords

amino

phenylmethyl

propyl

hydroxy

methylpropyl

Prior art date

1995-03-10

Links

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• 230000001177 retroviral effect Effects 0.000 title claims abstract description 19
• 239000000137 peptide hydrolase inhibitor Substances 0.000 title abstract description 8
• 229940042399 direct acting antivirals protease inhibitors Drugs 0.000 title abstract description 7
• JKTOKCJLZBURKJ-UHFFFAOYSA-N 1-hydroxy-2-(sulfamoylamino)ethane Chemical compound NS(=O)(=O)NCCO JKTOKCJLZBURKJ-UHFFFAOYSA-N 0.000 title 1
• 239000000203 mixture Substances 0.000 claims abstract description 131
• 238000000034 method Methods 0.000 claims abstract description 86
• 150000001875 compounds Chemical class 0.000 claims abstract description 70
• 108091005804 Peptidases Proteins 0.000 claims abstract description 22
• 239000004365 Protease Substances 0.000 claims abstract description 21
• 102100037486 Reverse transcriptase/ribonuclease H Human genes 0.000 claims abstract description 14
• 230000002401 inhibitory effect Effects 0.000 claims abstract description 10
• 238000011282 treatment Methods 0.000 claims abstract description 7
• 241001430294 unidentified retrovirus Species 0.000 claims abstract description 6
• 206010038997 Retroviral infections Diseases 0.000 claims abstract description 5
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 711
• -1 alkyl radical Chemical class 0.000 claims description 641
• 125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 claims description 399
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 377
• 125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 claims description 365
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 345
• 238000002360 preparation method Methods 0.000 claims description 128
• 229910052757 nitrogen Inorganic materials 0.000 claims description 75
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical class OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 claims description 68
• 125000004432 carbon atom Chemical group C* 0.000 claims description 52
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 44
• 229910052739 hydrogen Inorganic materials 0.000 claims description 39
• 239000001257 hydrogen Substances 0.000 claims description 39
• 150000003254 radicals Chemical class 0.000 claims description 37
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 34
• UHOVQNZJYSORNB-UHFFFAOYSA-N monobenzene Natural products C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 34
• 125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 claims description 29
• 150000003839 salts Chemical class 0.000 claims description 29
• KNEPBZMJMJUNQX-UHFFFAOYSA-N pent-4-ynamide Chemical compound NC(=O)CCC#C KNEPBZMJMJUNQX-UHFFFAOYSA-N 0.000 claims description 27
• 229910052717 sulfur Inorganic materials 0.000 claims description 23
• 125000000217 alkyl group Chemical group 0.000 claims description 22
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 claims description 20
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 20
• 125000004533 benzofuran-5-yl group Chemical group O1C=CC2=C1C=CC(=C2)* 0.000 claims description 20
• 125000003118 aryl group Chemical group 0.000 claims description 18
• 150000002431 hydrogen Chemical class 0.000 claims description 18
• 229910052760 oxygen Inorganic materials 0.000 claims description 18
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
• 150000002148 esters Chemical class 0.000 claims description 15
• AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical class CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 claims description 14
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical class OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 claims description 14
• 125000003710 aryl alkyl group Chemical group 0.000 claims description 14
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 14
• 150000003462 sulfoxides Chemical class 0.000 claims description 13
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 12
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 11
• 150000003457 sulfones Chemical class 0.000 claims description 11
• 125000003545 alkoxy group Chemical group 0.000 claims description 10
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 10
• 229910052799 carbon Inorganic materials 0.000 claims description 9
• 125000001072 heteroaryl group Chemical group 0.000 claims description 9
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 9
• 150000001204 N-oxides Chemical class 0.000 claims description 7
• 229910052805 deuterium Inorganic materials 0.000 claims description 7
• 125000001972 isopentyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])C([H])([H])* 0.000 claims description 7
• 239000001301 oxygen Substances 0.000 claims description 7
• 229910052720 vanadium Inorganic materials 0.000 claims description 7
• YZCKVEUIGOORGS-IGMARMGPSA-N Protium Chemical compound [1H] YZCKVEUIGOORGS-IGMARMGPSA-N 0.000 claims description 6
• 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 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
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
• 125000001424 substituent group Chemical group 0.000 claims description 6
• 125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 claims description 6
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 5
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 5
• 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 5
• 229910052740 iodine Inorganic materials 0.000 claims description 5
• YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 claims description 4
• 125000005605 benzo group Chemical group 0.000 claims description 4
• 125000006317 cyclopropyl amino group Chemical group 0.000 claims description 4
• 125000001559 cyclopropyl group Chemical group [H]C1([H])C([H])([H])C1([H])* 0.000 claims description 4
• 125000001153 fluoro group Chemical group F* 0.000 claims description 4
• 125000004475 heteroaralkyl group Chemical group 0.000 claims description 4
• 125000004029 hydroxymethyl group Chemical group [H]OC([H])([H])* 0.000 claims description 4
• 230000010076 replication Effects 0.000 claims description 4
• 125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 4
• 125000000954 2-hydroxyethyl group Chemical group [H]C([*])([H])C([H])([H])O[H] 0.000 claims description 3
• 125000004200 2-methoxyethyl group Chemical group [H]C([H])([H])OC([H])([H])C([H])([H])* 0.000 claims description 3
• 125000006479 2-pyridyl methyl group Chemical group [H]C1=C([H])C([H])=C([H])C(=N1)C([H])([H])* 0.000 claims description 3
• SLRMQYXOBQWXCR-UHFFFAOYSA-N 2154-56-5 Chemical compound [CH2]C1=CC=CC=C1 SLRMQYXOBQWXCR-UHFFFAOYSA-N 0.000 claims description 3
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical class OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 3
• DGYIJVNZSDYBOE-UHFFFAOYSA-N [CH2]C1=CC=NC=C1 Chemical group [CH2]C1=CC=NC=C1 DGYIJVNZSDYBOE-UHFFFAOYSA-N 0.000 claims description 3
• CIUQDSCDWFSTQR-UHFFFAOYSA-N [C]1=CC=CC=C1 Chemical compound [C]1=CC=CC=C1 CIUQDSCDWFSTQR-UHFFFAOYSA-N 0.000 claims description 3
• 125000004183 alkoxy alkyl group Chemical group 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
• 125000000582 cycloheptyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 claims description 3
• 125000004210 cyclohexylmethyl group Chemical group [H]C([H])(*)C1([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C1([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
• 125000004851 cyclopentylmethyl group Chemical group C1(CCCC1)C* 0.000 claims description 3
• 125000004184 methoxymethyl group Chemical group [H]C([H])([H])OC([H])([H])* 0.000 claims description 3
• 125000006729 (C2-C5) alkenyl group Chemical group 0.000 claims description 2
• 125000006730 (C2-C5) alkynyl group Chemical group 0.000 claims description 2
• GAWIXWVDTYZWAW-UHFFFAOYSA-N C[CH]O Chemical group C[CH]O GAWIXWVDTYZWAW-UHFFFAOYSA-N 0.000 claims description 2
• 125000004966 cyanoalkyl group Chemical group 0.000 claims description 2
• 125000002757 morpholinyl group Chemical group 0.000 claims description 2
• 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 2
• 125000003884 phenylalkyl group Chemical group 0.000 claims description 2
• 125000000286 phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims description 2
• 125000004193 piperazinyl group Chemical group 0.000 claims description 2
• 125000003386 piperidinyl group Chemical group 0.000 claims description 2
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 2
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims 113
• 125000004430 oxygen atom Chemical group O* 0.000 claims 6
• 125000004434 sulfur atom Chemical group 0.000 claims 6
• 239000003814 drug Substances 0.000 claims 4
• 125000004540 benzothiazol-5-yl group Chemical group S1C=NC2=C1C=CC(=C2)* 0.000 claims 3
• WCYWZMWISLQXQU-UHFFFAOYSA-N methyl Chemical compound [CH3] WCYWZMWISLQXQU-UHFFFAOYSA-N 0.000 claims 3
• KRHYYFGTRYWZRS-UHFFFAOYSA-N Fluorane Chemical compound F KRHYYFGTRYWZRS-UHFFFAOYSA-N 0.000 claims 2
• 125000006570 (C5-C6) heteroaryl group Chemical group 0.000 claims 1
• 125000000094 2-phenylethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])C([H])([H])* 0.000 claims 1
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims 1
• 208000030507 AIDS Diseases 0.000 claims 1
• SXCSNHUFLQAXDY-UHFFFAOYSA-N N-benzyl-2-tert-butylpentanamide Chemical compound C(CC)C(C(=O)NCC1=CC=CC=C1)C(C)(C)C SXCSNHUFLQAXDY-UHFFFAOYSA-N 0.000 claims 1
• 125000006350 alkyl thio alkyl group Chemical group 0.000 claims 1
• 125000005002 aryl methyl group Chemical group 0.000 claims 1
• 125000005164 aryl thioalkyl group Chemical group 0.000 claims 1
• HXCKCCRKGXHOBK-UHFFFAOYSA-N cycloheptane Chemical compound [CH]1CCCCCC1 HXCKCCRKGXHOBK-UHFFFAOYSA-N 0.000 claims 1
• 239000003937 drug carrier Substances 0.000 claims 1
• QUPDWYMUPZLYJZ-UHFFFAOYSA-N ethyl Chemical compound C[CH2] QUPDWYMUPZLYJZ-UHFFFAOYSA-N 0.000 claims 1
• 238000000338 in vitro Methods 0.000 claims 1
• 150000002688 maleic acid derivatives Chemical class 0.000 claims 1
• IGEIPFLJVCPEKU-UHFFFAOYSA-N pentan-2-amine Chemical compound CCCC(C)N IGEIPFLJVCPEKU-UHFFFAOYSA-N 0.000 claims 1
• 150000003016 phosphoric acids Chemical class 0.000 claims 1
• KDYFGRWQOYBRFD-UHFFFAOYSA-N succinic acid Chemical class OC(=O)CCC(O)=O KDYFGRWQOYBRFD-UHFFFAOYSA-N 0.000 claims 1
• 102000035195 Peptidases Human genes 0.000 abstract description 8
• 241000725303 Human immunodeficiency virus Species 0.000 abstract description 7
• 239000003112 inhibitor Substances 0.000 abstract description 7
• 108010010369 HIV Protease Proteins 0.000 abstract description 5
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 381
• 239000000243 solution Substances 0.000 description 198
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 189
• 235000019439 ethyl acetate Nutrition 0.000 description 129
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 123
• 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 116
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 110
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 108
• 239000000047 product Substances 0.000 description 92
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 77
• 239000002904 solvent Substances 0.000 description 65
• CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 63
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 63
• 239000007787 solid Substances 0.000 description 61
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 60
• 239000012267 brine Substances 0.000 description 57
• 239000011541 reaction mixture Substances 0.000 description 57
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 57
• 230000002829 reductive effect Effects 0.000 description 56
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 55
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 55
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 51
• 238000006243 chemical reaction Methods 0.000 description 49
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 48
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 43
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 40
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 39
• 238000007792 addition Methods 0.000 description 37
• MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 35
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 31
• 239000012044 organic layer Substances 0.000 description 31
• 229910052943 magnesium sulfate Inorganic materials 0.000 description 28
• 235000019341 magnesium sulphate Nutrition 0.000 description 28
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 26
• KDLHZDBZIXYQEI-UHFFFAOYSA-N palladium Substances [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 26
• 150000001412 amines Chemical class 0.000 description 25
• SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 24
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 24
• 238000003756 stirring Methods 0.000 description 24
• BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 23
• 238000004128 high performance liquid chromatography Methods 0.000 description 23
• 239000010410 layer Substances 0.000 description 23
• 235000015165 citric acid Nutrition 0.000 description 22
• 239000012043 crude product Substances 0.000 description 22
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 21
• 125000002668 chloroacetyl group Chemical group ClCC(=O)* 0.000 description 21
• 229920006395 saturated elastomer Polymers 0.000 description 21
• 239000000741 silica gel Substances 0.000 description 21
• 229910002027 silica gel Inorganic materials 0.000 description 21
• 238000001914 filtration Methods 0.000 description 20
• IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 19
• 229910000041 hydrogen chloride Inorganic materials 0.000 description 19
• 239000003921 oil Substances 0.000 description 19
• 239000003054 catalyst Substances 0.000 description 18
• 229940024606 amino acid Drugs 0.000 description 17
• 239000000706 filtrate Substances 0.000 description 17
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 16
• KDSNLYIMUZNERS-UHFFFAOYSA-N 2-methylpropanamine Chemical compound CC(C)CN KDSNLYIMUZNERS-UHFFFAOYSA-N 0.000 description 16
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 16
• 239000002253 acid Substances 0.000 description 16
• 239000000460 chlorine Substances 0.000 description 16
• 238000000746 purification Methods 0.000 description 16
• 235000017557 sodium bicarbonate Nutrition 0.000 description 16
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 16
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 15
• 150000001299 aldehydes Chemical class 0.000 description 15
• 235000001014 amino acid Nutrition 0.000 description 15
• NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 15
• WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 14
• 239000003153 chemical reaction reagent Substances 0.000 description 14
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 13
• PJGJQVRXEUVAFT-UHFFFAOYSA-N chloroiodomethane Chemical compound ClCI PJGJQVRXEUVAFT-UHFFFAOYSA-N 0.000 description 13
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 12
• UIIMBOGNXHQVGW-DEQYMQKBSA-M Sodium bicarbonate-14C Chemical compound [Na+].O[14C]([O-])=O UIIMBOGNXHQVGW-DEQYMQKBSA-M 0.000 description 12
• JPOXNPPZZKNXOV-UHFFFAOYSA-N bromochloromethane Chemical compound ClCBr JPOXNPPZZKNXOV-UHFFFAOYSA-N 0.000 description 12
• 229910052698 phosphorus Inorganic materials 0.000 description 12
• 239000000843 powder Substances 0.000 description 12
• 235000019419 proteases Nutrition 0.000 description 12
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 11
• 239000000543 intermediate Substances 0.000 description 11
• 238000010898 silica gel chromatography Methods 0.000 description 11
• PNVPNXKRAUBJGW-UHFFFAOYSA-N (2-chloroacetyl) 2-chloroacetate Chemical compound ClCC(=O)OC(=O)CCl PNVPNXKRAUBJGW-UHFFFAOYSA-N 0.000 description 10
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 10
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 10
• 150000001413 amino acids Chemical class 0.000 description 10
• 238000004587 chromatography analysis Methods 0.000 description 10
• 239000013058 crude material Substances 0.000 description 10
• CTSLXHKWHWQRSH-UHFFFAOYSA-N oxalyl chloride Chemical compound ClC(=O)C(Cl)=O CTSLXHKWHWQRSH-UHFFFAOYSA-N 0.000 description 10
• 238000010992 reflux Methods 0.000 description 10
• 239000007858 starting material Substances 0.000 description 10
• 239000000725 suspension Substances 0.000 description 10
• ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 9
• 238000005481 NMR spectroscopy Methods 0.000 description 9
• 150000001414 amino alcohols Chemical class 0.000 description 9
• 239000002585 base Substances 0.000 description 9
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 9
• 238000004992 fast atom bombardment mass spectroscopy Methods 0.000 description 9
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 9
• 239000012299 nitrogen atmosphere Substances 0.000 description 9
• 150000002924 oxiranes Chemical class 0.000 description 9
• 150000008575 L-amino acids Chemical class 0.000 description 8
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
• 229960000583 acetic acid Drugs 0.000 description 8
• 125000003277 amino group Chemical group 0.000 description 8
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 8
• 229910052801 chlorine Inorganic materials 0.000 description 8
• 238000001816 cooling Methods 0.000 description 8
• 239000010779 crude oil Substances 0.000 description 8
• 230000014759 maintenance of location Effects 0.000 description 8
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