CA2262818A1 - Modified amino acids, pharmaceuticals containing these compounds and methods for their production - Google Patents

Info

Publication number

CA2262818A1

CA2262818A1 CA002262818A CA2262818A CA2262818A1 CA 2262818 A1 CA2262818 A1 CA 2262818A1 CA 002262818 A CA002262818 A CA 002262818A CA 2262818 A CA2262818 A CA 2262818A CA 2262818 A1 CA2262818 A1 CA 2262818A1

Authority

CA

Canada

Prior art keywords

group

dihydro

denotes

phenyl

groups

Prior art date

1996-09-10

Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)

Abandoned

Links

• Espacenet
• Global Dossier
• CIPO
• Discuss

• 150000001875 compounds Chemical class 0.000 title claims abstract description 117
• 238000000034 method Methods 0.000 title claims abstract description 32
• 150000001413 amino acids Chemical class 0.000 title claims abstract description 22
• 238000004519 manufacturing process Methods 0.000 title claims abstract description 7
• 239000003814 drug Chemical class 0.000 title abstract description 4
• 239000000203 mixture Substances 0.000 claims abstract description 53
• 150000003839 salts Chemical class 0.000 claims abstract description 35
• 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 abstract description 17
• 238000000746 purification Methods 0.000 claims abstract description 15
• 150000007522 mineralic acids Chemical class 0.000 claims abstract description 4
• 150000007524 organic acids Chemical class 0.000 claims abstract description 4
• 235000005985 organic acids Nutrition 0.000 claims abstract description 4
• 238000012286 ELISA Assay Methods 0.000 claims abstract description 3
• 239000002858 neurotransmitter agent Substances 0.000 claims abstract description 3
• 238000011160 research Methods 0.000 claims abstract description 3
• -1 biphenylyl group Chemical group 0.000 claims description 1050
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 584
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 289
• 125000004433 nitrogen atom Chemical group N* 0.000 claims description 269
• 229910052757 nitrogen Inorganic materials 0.000 claims description 258
• 125000000217 alkyl group Chemical group 0.000 claims description 210
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 173
• 229910052799 carbon Inorganic materials 0.000 claims description 148
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 147
• 150000001721 carbon Chemical group 0.000 claims description 138
• 125000004076 pyridyl group Chemical group 0.000 claims description 120
• 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 112
• 239000000460 chlorine Substances 0.000 claims description 107
• 229910052801 chlorine Inorganic materials 0.000 claims description 106
• 239000011737 fluorine Substances 0.000 claims description 100
• 229910052731 fluorine Inorganic materials 0.000 claims description 100
• 125000001424 substituent group Chemical group 0.000 claims description 98
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 86
• 125000004432 carbon atom Chemical group C* 0.000 claims description 86
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 78
• 125000003545 alkoxy group Chemical group 0.000 claims description 72
• OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 68
• 125000001589 carboacyl group Chemical group 0.000 claims description 68
• 125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 65
• 125000001246 bromo group Chemical group Br* 0.000 claims description 64
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 63
• 125000001072 heteroaryl group Chemical group 0.000 claims description 61
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims description 59
• 125000001637 1-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C(*)=C([H])C([H])=C([H])C2=C1[H] 0.000 claims description 55
• 229910052760 oxygen Inorganic materials 0.000 claims description 55
• NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims description 54
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 54
• 239000001301 oxygen Substances 0.000 claims description 54
• 125000005331 diazinyl group Chemical group N1=NC(=CC=C1)* 0.000 claims description 53
• 125000005078 alkoxycarbonylalkyl group Chemical group 0.000 claims description 52
• 125000001622 2-naphthyl group Chemical group [H]C1=C([H])C([H])=C2C([H])=C(*)C([H])=C([H])C2=C1[H] 0.000 claims description 50
• 125000003282 alkyl amino group Chemical group 0.000 claims description 50
• 125000004093 cyano group Chemical group *C#N 0.000 claims description 49
• 125000004181 carboxyalkyl group Chemical group 0.000 claims description 48
• 125000006239 protecting group Chemical group 0.000 claims description 48
• 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 claims description 45
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 45
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 claims description 42
• 125000004457 alkyl amino carbonyl group Chemical group 0.000 claims description 42
• 125000001153 fluoro group Chemical group F* 0.000 claims description 41
• 125000000814 indol-3-yl group Chemical group [H]C1=C([H])C([H])=C2N([H])C([H])=C([*])C2=C1[H] 0.000 claims description 41
• 125000000623 heterocyclic group Chemical group 0.000 claims description 40
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims description 39
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 39
• KZBUYRJDOAKODT-UHFFFAOYSA-N Chlorine Chemical compound ClCl KZBUYRJDOAKODT-UHFFFAOYSA-N 0.000 claims description 38
• 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 37
• 125000004985 dialkyl amino alkyl group Chemical group 0.000 claims description 36
• 125000004663 dialkyl amino group Chemical group 0.000 claims description 35
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 35
• 125000000738 acetamido group Chemical group [H]C([H])([H])C(=O)N([H])[*] 0.000 claims description 34
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 33
• 125000001624 naphthyl group Chemical group 0.000 claims description 33
• 125000006273 (C1-C3) alkyl group Chemical group 0.000 claims description 30
• 125000001841 imino group Chemical group [H]N=* 0.000 claims description 30
• 125000002950 monocyclic group Chemical group 0.000 claims description 30
• 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 30
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 29
• 125000004473 dialkylaminocarbonyl group Chemical group 0.000 claims description 28
• 125000002071 phenylalkoxy group Chemical group 0.000 claims description 28
• 238000006467 substitution reaction Methods 0.000 claims description 28
• 238000006243 chemical reaction Methods 0.000 claims description 27
• 125000004548 quinolin-3-yl group Chemical group N1=CC(=CC2=CC=CC=C12)* 0.000 claims description 27
• 125000006598 aminocarbonylamino group Chemical group 0.000 claims description 26
• 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 24
• 239000005864 Sulphur Substances 0.000 claims description 24
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 24
• 125000002541 furyl group Chemical group 0.000 claims description 24
• 239000002243 precursor Substances 0.000 claims description 24
• 125000000876 trifluoromethoxy group Chemical group FC(F)(F)O* 0.000 claims description 24
• YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 22
• 125000004949 alkyl amino carbonyl amino group Chemical group 0.000 claims description 20
• 125000000587 piperidin-1-yl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 20
• 125000001544 thienyl group Chemical group 0.000 claims description 19
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 18
• 125000003118 aryl group Chemical group 0.000 claims description 17
• 239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 16
• 125000002883 imidazolyl group Chemical group 0.000 claims description 16
• 125000000842 isoxazolyl group Chemical group 0.000 claims description 16
• 125000003884 phenylalkyl group Chemical group 0.000 claims description 16
• 125000000168 pyrrolyl group Chemical group 0.000 claims description 16
• 125000000335 thiazolyl group Chemical group 0.000 claims description 16
• 125000005034 trifluormethylthio group Chemical group FC(S*)(F)F 0.000 claims description 16
• 125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 claims description 15
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 15
• 229920006395 saturated elastomer Polymers 0.000 claims description 15
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 14
• SMWDFEZZVXVKRB-UHFFFAOYSA-N Quinoline Chemical compound N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 14
• 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 claims description 14
• 108090000765 processed proteins & peptides Proteins 0.000 claims description 14
• 125000002943 quinolinyl group Chemical group N1=C(C=CC2=CC=CC=C12)* 0.000 claims description 14
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 13
• 125000004430 oxygen atom Chemical group O* 0.000 claims description 13
• 125000004890 (C1-C6) alkylamino group Chemical group 0.000 claims description 12
• YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 claims description 12
• 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 claims description 12
• 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 11
• 239000002253 acid Substances 0.000 claims description 11
• 125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 11
• 150000001412 amines Chemical class 0.000 claims description 11
• 125000000043 benzamido group Chemical group [H]N([*])C(=O)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 11
• 125000004744 butyloxycarbonyl group Chemical group 0.000 claims description 11
• 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 11
• 125000004458 methylaminocarbonyl group Chemical group [H]N(C(*)=O)C([H])([H])[H] 0.000 claims description 11
• KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims description 10
• 125000002618 bicyclic heterocycle group Chemical group 0.000 claims description 10
• 150000001735 carboxylic acids Chemical class 0.000 claims description 10
• 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 10
• 125000002183 isoquinolinyl group Chemical group C1(=NC=CC2=CC=CC=C12)* 0.000 claims description 10
• 125000002911 monocyclic heterocycle group Chemical group 0.000 claims description 10
• 125000001541 3-thienyl group Chemical group S1C([H])=C([*])C([H])=C1[H] 0.000 claims description 9
• WSFSSNUMVMOOMR-UHFFFAOYSA-N Formaldehyde Chemical compound O=C WSFSSNUMVMOOMR-UHFFFAOYSA-N 0.000 claims description 9
• 125000004103 aminoalkyl group Chemical group 0.000 claims description 9
• 125000002490 anilino group Chemical group [H]N(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 claims description 9
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 9
• 125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 claims description 9
• 238000002360 preparation method Methods 0.000 claims description 9
• 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 claims description 8
• 125000000278 alkyl amino alkyl group Chemical group 0.000 claims description 8
• 150000004649 carbonic acid derivatives Chemical class 0.000 claims description 8
• 125000001316 cycloalkyl alkyl group Chemical group 0.000 claims description 8
• 125000003386 piperidinyl group Chemical group 0.000 claims description 8
• 125000003226 pyrazolyl group Chemical group 0.000 claims description 8
• MCTWTZJPVLRJOU-UHFFFAOYSA-N 1-methyl-1H-imidazole Chemical compound CN1C=CN=C1 MCTWTZJPVLRJOU-UHFFFAOYSA-N 0.000 claims description 7
• 125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 7
• 125000002057 carboxymethyl group Chemical group [H]OC(=O)C([H])([H])[*] 0.000 claims description 7
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 7
• 125000000389 2-pyrrolyl group Chemical group [H]N1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
• 125000001397 3-pyrrolyl group Chemical group [H]N1C([H])=C([*])C([H])=C1[H] 0.000 claims description 6
• 125000002723 alicyclic group Chemical group 0.000 claims description 6
• 125000005079 alkoxycarbonylmethyl group Chemical group 0.000 claims description 6
• 125000005605 benzo group Chemical group 0.000 claims description 6
• 125000002619 bicyclic group Chemical group 0.000 claims description 6
• 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 6
• 125000002757 morpholinyl group Chemical group 0.000 claims description 6
• 125000000719 pyrrolidinyl group Chemical group 0.000 claims description 6
• 239000000126 substance Substances 0.000 claims description 6
• 229930192474 thiophene Natural products 0.000 claims description 6
• 125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 5
• 125000004414 alkyl thio group Chemical group 0.000 claims description 5
• 125000003435 aroyl group Chemical group 0.000 claims description 5
• 125000006297 carbonyl amino group Chemical group [H]N([*:2])C([*:1])=O 0.000 claims description 5
• 239000012948 isocyanate Substances 0.000 claims description 5
• 150000002513 isocyanates Chemical class 0.000 claims description 5
• 125000000391 vinyl group Chemical group [H]C([*])=C([H])[H] 0.000 claims description 5
• 229920002554 vinyl polymer Polymers 0.000 claims description 5
• 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 4
• FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical compound C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 4
• 125000002252 acyl group Chemical group 0.000 claims description 4
• 125000003342 alkenyl group Chemical group 0.000 claims description 4
• 125000004656 alkyl sulfonylamino group Chemical group 0.000 claims description 4
• 125000005097 aminocarbonylalkyl group Chemical group 0.000 claims description 4
• 239000004202 carbamide Substances 0.000 claims description 4
• 125000001309 chloro group Chemical group Cl* 0.000 claims description 4
• 125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 4
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 4
• BQJCRHHNABKAKU-KBQPJGBKSA-N morphine Chemical compound O([C@H]1[C@H](C=C[C@H]23)O)C4=C5[C@@]12CCN(C)[C@@H]3CC5=CC=C4O BQJCRHHNABKAKU-KBQPJGBKSA-N 0.000 claims description 4
• 239000008194 pharmaceutical composition Substances 0.000 claims description 4
• SEEPANYCNGTZFQ-UHFFFAOYSA-N sulfadiazine Chemical compound C1=CC(N)=CC=C1S(=O)(=O)NC1=NC=CC=N1 SEEPANYCNGTZFQ-UHFFFAOYSA-N 0.000 claims description 4
• 125000003831 tetrazolyl group Chemical group 0.000 claims description 4
• OXHNLMTVIGZXSG-UHFFFAOYSA-N 1-Methylpyrrole Chemical compound CN1C=CC=C1 OXHNLMTVIGZXSG-UHFFFAOYSA-N 0.000 claims description 3
• ZCQWOFVYLHDMMC-UHFFFAOYSA-N Oxazole Chemical compound C1=COC=N1 ZCQWOFVYLHDMMC-UHFFFAOYSA-N 0.000 claims description 3
• 125000003277 amino group Chemical group 0.000 claims description 3
• 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 claims description 3
• 125000004984 dialkylaminoalkoxy group Chemical group 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• 201000010099 disease Diseases 0.000 claims description 3
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 claims description 3
• UYWQUFXKFGHYNT-UHFFFAOYSA-N phenylmethyl ester of formic acid Natural products O=COCC1=CC=CC=C1 UYWQUFXKFGHYNT-UHFFFAOYSA-N 0.000 claims description 3
• 208000001072 type 2 diabetes mellitus Diseases 0.000 claims description 3
• 125000004080 3-carboxypropanoyl group Chemical group O=C([*])C([H])([H])C([H])([H])C(O[H])=O 0.000 claims description 2
• 208000024172 Cardiovascular disease Diseases 0.000 claims description 2
• 206010019233 Headaches Diseases 0.000 claims description 2
• 206010039085 Rhinitis allergic Diseases 0.000 claims description 2
• 206010040047 Sepsis Diseases 0.000 claims description 2
• 230000001154 acute effect Effects 0.000 claims description 2
• 201000010105 allergic rhinitis Diseases 0.000 claims description 2
• 208000006673 asthma Diseases 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
• 125000002795 guanidino group Chemical group C(N)(=N)N* 0.000 claims description 2
• 231100000869 headache Toxicity 0.000 claims description 2
• 125000001041 indolyl group Chemical group 0.000 claims description 2
• 208000027866 inflammatory disease Diseases 0.000 claims description 2
• 229960005181 morphine Drugs 0.000 claims description 2
• 125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 2
• 238000011321 prophylaxis Methods 0.000 claims description 2
• 230000035939 shock Effects 0.000 claims description 2
• 208000017520 skin disease Diseases 0.000 claims description 2
• 230000024883 vasodilation Effects 0.000 claims description 2
• 125000006546 (C4-C10) cycloalkyl group Chemical group 0.000 claims 8
• 125000006705 (C5-C7) cycloalkyl group Chemical group 0.000 claims 7
• 125000006701 (C1-C7) alkyl group Chemical group 0.000 claims 6
• 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims 5
• 239000000969 carrier Substances 0.000 claims 2
• 125000006274 (C1-C3)alkoxy group Chemical group 0.000 claims 1
• 206010047141 Vasodilatation Diseases 0.000 claims 1
• 230000017531 blood circulation Effects 0.000 claims 1
• 210000004013 groin Anatomy 0.000 claims 1
• 125000000467 secondary amino group Chemical class [H]N([*:1])[*:2] 0.000 claims 1
• 239000002585 base Substances 0.000 abstract description 17
• 239000012752 auxiliary agent Substances 0.000 abstract description 2
• 235000001014 amino acid Nutrition 0.000 abstract 1
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 87
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 72
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 49
• 125000002435 L-phenylalanyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 47
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 42
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 30
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 30
• 235000002639 sodium chloride Nutrition 0.000 description 30
• 239000002904 solvent Substances 0.000 description 30
• 239000000243 solution Substances 0.000 description 26
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
• 239000013078 crystal Substances 0.000 description 24
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 24
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 18
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 18
• 238000010168 coupling process Methods 0.000 description 17
• 235000019439 ethyl acetate Nutrition 0.000 description 17
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 16
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 16
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 16
• 230000008878 coupling Effects 0.000 description 16
• 238000005859 coupling reaction Methods 0.000 description 16
• GLUUGHFHXGJENI-UHFFFAOYSA-N Piperazine Chemical compound C1CNCCN1 GLUUGHFHXGJENI-UHFFFAOYSA-N 0.000 description 15
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 14
• SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 14
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 12
• 229940024606 amino acid Drugs 0.000 description 12
• FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-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
• 125000004189 3,4-dichlorophenyl group Chemical group [H]C1=C([H])C(Cl)=C(Cl)C([H])=C1* 0.000 description 9
• 125000004207 3-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C([H])C(OC([H])([H])[H])=C1[H] 0.000 description 9
• 125000003798 L-tyrosyl group Chemical group [H]N([H])[C@]([H])(C(=O)[*])C([H])([H])C1=C([H])C([H])=C(O[H])C([H])=C1[H] 0.000 description 9
• KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 9
• 239000000706 filtrate Substances 0.000 description 9
• 238000002844 melting Methods 0.000 description 9
• 230000008018 melting Effects 0.000 description 9
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 8
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