TWI461426B

TWI461426B - （二氫）咪唑並異〔５，１－ａ〕喹啉類

（二氫）咪唑並異〔５，１－ａ〕喹啉類 Download PDF

Info

Publication number: TWI461426B
Authority: TW; Taiwan
Prior art keywords: alkyl; group; vacuo; concentrated; methoxy
Prior art date: 2009-05-27

Application number

TW099114528A

Other languages

English (en)

Chinese (zh)

Other versions

TW201107322A (en

Inventor

Hubert Jan Jozef Loozen

Cornelis Marius Timmers

Original Assignee

Merck Sharp & Dohme

Priority date

2009-05-27

Filing date

2010-05-06

Publication date

2014-11-21

2010-05-06 Application filed by Merck Sharp & Dohme filed Critical Merck Sharp & Dohme

2011-03-01 Publication of TW201107322A publication Critical patent/TW201107322A/zh

2014-11-21 Application granted granted Critical

2014-11-21 Publication of TWI461426B publication Critical patent/TWI461426B/zh

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150000003248 quinolines Chemical class 0.000 title description 14
229940111121 antirheumatic drug quinolines Drugs 0.000 title description 8
125000000217 alkyl group Chemical group 0.000 claims description 146
-1 quinoline compound Chemical class 0.000 claims description 109
150000001875 compounds Chemical class 0.000 claims description 108
125000003545 alkoxy group Chemical group 0.000 claims description 43
125000000592 heterocycloalkyl group Chemical group 0.000 claims description 43
125000001072 heteroaryl group Chemical group 0.000 claims description 35
229910052736 halogen Inorganic materials 0.000 claims description 34
150000002367 halogens Chemical class 0.000 claims description 34
125000001424 substituent group Chemical group 0.000 claims description 30
125000003277 amino group Chemical group 0.000 claims description 26
125000003342 alkenyl group Chemical group 0.000 claims description 24
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 23
150000003839 salts Chemical class 0.000 claims description 23
AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 21
125000004093 cyano group Chemical group *C#N 0.000 claims description 20
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 20
125000004448 alkyl carbonyl group Chemical group 0.000 claims description 19
125000004414 alkyl thio group Chemical group 0.000 claims description 19
229920006395 saturated elastomer Polymers 0.000 claims description 19
125000003806 alkyl carbonyl amino group Chemical group 0.000 claims description 18
125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 14
125000000304 alkynyl group Chemical group 0.000 claims description 13
SMWDFEZZVXVKRB-UHFFFAOYSA-N anhydrous quinoline Natural products N1=CC=CC2=CC=CC=C21 SMWDFEZZVXVKRB-UHFFFAOYSA-N 0.000 claims description 13
125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 12
125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims description 12
125000000753 cycloalkyl group Chemical group 0.000 claims description 12
125000004453 alkoxycarbonyl group Chemical group 0.000 claims description 11
125000006254 cycloalkyl carbonyl group Chemical group 0.000 claims description 10
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 10
XEEYBQQBJWHFJM-UHFFFAOYSA-N Iron Chemical compound [Fe] XEEYBQQBJWHFJM-UHFFFAOYSA-N 0.000 claims description 8
125000004466 alkoxycarbonylamino group Chemical group 0.000 claims description 8
150000001412 amines Chemical class 0.000 claims description 8
239000003814 drug Substances 0.000 claims description 8
125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 8
125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 8
125000004390 alkyl sulfonyl group Chemical group 0.000 claims description 7
150000001540 azides Chemical class 0.000 claims description 7
125000000000 cycloalkoxy group Chemical group 0.000 claims description 7
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 claims description 6
125000005553 heteroaryloxy group Chemical group 0.000 claims description 6
238000004519 manufacturing process Methods 0.000 claims description 6
239000008194 pharmaceutical composition Substances 0.000 claims description 6
125000006598 aminocarbonylamino group Chemical group 0.000 claims description 5
125000000392 cycloalkenyl group Chemical group 0.000 claims description 5
125000005241 heteroarylamino group Chemical group 0.000 claims description 5
125000005224 heteroarylcarbonylamino group Chemical group 0.000 claims description 5
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 5
229910052760 oxygen Inorganic materials 0.000 claims description 5
125000000951 phenoxy group Chemical group [H]C1=C([H])C([H])=C(O*)C([H])=C1[H] 0.000 claims description 5
150000001335 aliphatic alkanes Chemical class 0.000 claims description 4
239000001301 oxygen Substances 0.000 claims description 3
OWIKHYCFFJSOEH-UHFFFAOYSA-N Isocyanic acid Chemical group N=C=O OWIKHYCFFJSOEH-UHFFFAOYSA-N 0.000 claims description 2
QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 2
SFZULDYEOVSIKM-UHFFFAOYSA-N chembl321317 Chemical compound C1=CC(C(=N)NO)=CC=C1C1=CC=C(C=2C=CC(=CC=2)C(=N)NO)O1 SFZULDYEOVSIKM-UHFFFAOYSA-N 0.000 claims description 2
125000004496 thiazol-5-yl group Chemical group S1C=NC=C1* 0.000 claims description 2
KAESVJOAVNADME-UHFFFAOYSA-N 1H-pyrrole Natural products C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 claims 1
125000005169 cycloalkylcarbonylamino group Chemical group 0.000 claims 1
125000001475 halogen functional group Chemical group 0.000 claims 1
239000000546 pharmaceutical excipient Substances 0.000 claims 1
125000003396 thiol group Chemical class [H]S* 0.000 claims 1
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 755
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 327
235000019439 ethyl acetate Nutrition 0.000 description 274
239000000047 product Substances 0.000 description 211
IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 192
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 183
239000000203 mixture Substances 0.000 description 174
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 171
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 170
239000011541 reaction mixture Substances 0.000 description 170
239000000243 solution Substances 0.000 description 132
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 118
239000012044 organic layer Substances 0.000 description 104
238000005160 1H NMR spectroscopy Methods 0.000 description 103
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 102
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 98
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 93
238000004587 chromatography analysis Methods 0.000 description 89
238000003756 stirring Methods 0.000 description 86
229930192474 thiophene Natural products 0.000 description 85
125000002485 formyl group Chemical group [H]C(*)=O 0.000 description 83
238000004809 thin layer chromatography Methods 0.000 description 71
239000012267 brine Substances 0.000 description 67
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 67
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 56
239000007787 solid Substances 0.000 description 56
125000004432 carbon atom Chemical group C* 0.000 description 50
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 45
238000000034 method Methods 0.000 description 43
239000000460 chlorine Substances 0.000 description 41
239000002904 solvent Substances 0.000 description 40
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical class OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 37
239000012317 TBTU Substances 0.000 description 37
CLZISMQKJZCZDN-UHFFFAOYSA-N [benzotriazol-1-yloxy(dimethylamino)methylidene]-dimethylazanium Chemical compound C1=CC=C2N(OC(N(C)C)=[N+](C)C)N=NC2=C1 CLZISMQKJZCZDN-UHFFFAOYSA-N 0.000 description 37
238000005481 NMR spectroscopy Methods 0.000 description 36
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 29
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 29
239000001307 helium Substances 0.000 description 29
229910052734 helium Inorganic materials 0.000 description 29
SWQJXJOGLNCZEY-UHFFFAOYSA-N helium atom Chemical compound [He] SWQJXJOGLNCZEY-UHFFFAOYSA-N 0.000 description 29
JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 28
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 28
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 description 27
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 27
239000000725 suspension Substances 0.000 description 27
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 25
229910052943 magnesium sulfate Inorganic materials 0.000 description 25
IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 24
238000006243 chemical reaction Methods 0.000 description 22
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 22
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
210000004027 cell Anatomy 0.000 description 20
239000008188 pellet Substances 0.000 description 19
AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 18
DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 17
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 17
238000002953 preparative HPLC Methods 0.000 description 16
ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 15
229910052757 nitrogen Inorganic materials 0.000 description 15
108010060374 FSH Receptors Proteins 0.000 description 14
230000015572 biosynthetic process Effects 0.000 description 14
239000000706 filtrate Substances 0.000 description 14
RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 14
ZQGJEUVBUVKZKS-UHFFFAOYSA-N n,2-dimethylpropan-2-amine Chemical compound CNC(C)(C)C ZQGJEUVBUVKZKS-UHFFFAOYSA-N 0.000 description 14
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 14
239000012453 solvate Substances 0.000 description 14
238000003786 synthesis reaction Methods 0.000 description 14
BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 13
XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 12
102000008175 FSH Receptors Human genes 0.000 description 12
102000012673 Follicle Stimulating Hormone Human genes 0.000 description 12
108010079345 Follicle Stimulating Hormone Proteins 0.000 description 12
229910052799 carbon Inorganic materials 0.000 description 12
125000005842 heteroatom Chemical group 0.000 description 12
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 12
229910000041 hydrogen chloride Inorganic materials 0.000 description 12
239000010410 layer Substances 0.000 description 12
102000005962 receptors Human genes 0.000 description 12
108020003175 receptors Proteins 0.000 description 12
MZRVEZGGRBJDDB-UHFFFAOYSA-N N-Butyllithium Chemical compound [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 11
ZMNWMAGZLQKXFS-UHFFFAOYSA-N N-tert-butyl-N-methyldecan-1-amine Chemical compound CCCCCCCCCCN(C)C(C)(C)C ZMNWMAGZLQKXFS-UHFFFAOYSA-N 0.000 description 11
230000008878 coupling Effects 0.000 description 11
238000010168 coupling process Methods 0.000 description 11
238000005859 coupling reaction Methods 0.000 description 11
239000003480 eluent Substances 0.000 description 11
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 11
239000000651 prodrug Substances 0.000 description 11
229940002612 prodrug Drugs 0.000 description 11
125000001544 thienyl group Chemical group 0.000 description 11
DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 11
239000002253 acid Substances 0.000 description 10
239000002585 base Substances 0.000 description 10
229940028334 follicle stimulating hormone Drugs 0.000 description 10
NDMFETHQFUOIQX-UHFFFAOYSA-N 1-(3-chloropropyl)imidazolidin-2-one Chemical compound ClCCCN1CCNC1=O NDMFETHQFUOIQX-UHFFFAOYSA-N 0.000 description 9
QGFYFOHMBDMGBZ-UHFFFAOYSA-N 5-[(7-chloroquinolin-4-yl)amino]-2-(diethylaminomethyl)phenol Chemical compound C1=C(O)C(CN(CC)CC)=CC=C1NC1=CC=NC2=CC(Cl)=CC=C12 QGFYFOHMBDMGBZ-UHFFFAOYSA-N 0.000 description 9
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 9
150000001721 carbon Chemical group 0.000 description 9
UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 9
239000005457 ice water Substances 0.000 description 9
229940098779 methanesulfonic acid Drugs 0.000 description 9
239000011734 sodium Substances 0.000 description 9
229910000104 sodium hydride Inorganic materials 0.000 description 9
230000000638 stimulation Effects 0.000 description 9
238000012360 testing method Methods 0.000 description 9
HVCNXQOWACZAFN-UHFFFAOYSA-N 4-ethylmorpholine Chemical compound CCN1CCOCC1 HVCNXQOWACZAFN-UHFFFAOYSA-N 0.000 description 8
238000001914 filtration Methods 0.000 description 8
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 8
125000003253 isopropoxy group Chemical group [H]C([H])([H])C([H])(O*)C([H])([H])[H] 0.000 description 8
125000004076 pyridyl group Chemical group 0.000 description 8
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 description 8
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 7
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 7
230000027455 binding Effects 0.000 description 7
230000000694 effects Effects 0.000 description 7
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
230000014509 gene expression Effects 0.000 description 7
RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 description 7
239000000843 powder Substances 0.000 description 7
OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 description 6
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 6
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 6
238000001035 drying Methods 0.000 description 6
235000019253 formic acid Nutrition 0.000 description 6
125000002883 imidazolyl group Chemical group 0.000 description 6
AWJUIBRHMBBTKR-UHFFFAOYSA-N isoquinoline Chemical compound C1=NC=CC2=CC=CC=C21 AWJUIBRHMBBTKR-UHFFFAOYSA-N 0.000 description 6
DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 6
230000016087 ovulation Effects 0.000 description 6
RWRDLPDLKQPQOW-UHFFFAOYSA-N tetrahydropyrrole Natural products C1CCNC1 RWRDLPDLKQPQOW-UHFFFAOYSA-N 0.000 description 6
238000001946 ultra-performance liquid chromatography-mass spectrometry Methods 0.000 description 6
DXJSJHFRGIYTJZ-UHFFFAOYSA-N 5-butyl-5-(5-butylnonan-5-yloxy)nonane Chemical compound CCCCC(CCCC)(CCCC)OC(CCCC)(CCCC)CCCC DXJSJHFRGIYTJZ-UHFFFAOYSA-N 0.000 description 5
108020004414 DNA Proteins 0.000 description 5
102000003864 Human Follicle Stimulating Hormone Human genes 0.000 description 5
108010082302 Human Follicle Stimulating Hormone Proteins 0.000 description 5
NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 5
108700008625 Reporter Genes Proteins 0.000 description 5
239000007864 aqueous solution Substances 0.000 description 5
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 5
239000003153 chemical reaction reagent Substances 0.000 description 5
239000006185 dispersion Substances 0.000 description 5
150000002148 esters Chemical class 0.000 description 5
208000000509 infertility Diseases 0.000 description 5
230000036512 infertility Effects 0.000 description 5
231100000535 infertility Toxicity 0.000 description 5
125000004573 morpholin-4-yl group Chemical group N1(CCOCC1)* 0.000 description 5
230000002611 ovarian Effects 0.000 description 5
230000003647 oxidation Effects 0.000 description 5
238000007254 oxidation reaction Methods 0.000 description 5
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 description 5
238000002360 preparation method Methods 0.000 description 5
ANOUKFYBOAKOIR-UHFFFAOYSA-N 3,4-dimethoxyphenylethylamine Chemical compound COC1=CC=C(CCN)C=C1OC ANOUKFYBOAKOIR-UHFFFAOYSA-N 0.000 description 4
WBZLGNODHLEZLU-UHFFFAOYSA-N 5,6-dihydroimidazo[5,1-a]isoquinoline Chemical class C12=CC=CC=C2CCN2C1=CN=C2 WBZLGNODHLEZLU-UHFFFAOYSA-N 0.000 description 4
NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 4
OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 description 4
102000006771 Gonadotropins Human genes 0.000 description 4
108010086677 Gonadotropins Proteins 0.000 description 4
OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 4
BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical class NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 4
OLBVUFHMDRJKTK-UHFFFAOYSA-N [N].[O] Chemical compound [N].[O] OLBVUFHMDRJKTK-UHFFFAOYSA-N 0.000 description 4
230000001270 agonistic effect Effects 0.000 description 4
150000001299 aldehydes Chemical class 0.000 description 4
125000004429 atom Chemical group 0.000 description 4
150000004985 diamines Chemical class 0.000 description 4
OJCSPXHYDFONPU-UHFFFAOYSA-N etoac etoac Chemical compound CCOC(C)=O.CCOC(C)=O OJCSPXHYDFONPU-UHFFFAOYSA-N 0.000 description 4
125000002541 furyl group Chemical group 0.000 description 4
239000002622 gonadotropin Substances 0.000 description 4
229940094892 gonadotropins Drugs 0.000 description 4
NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 4
150000002576 ketones Chemical class 0.000 description 4
JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 description 4
238000006138 lithiation reaction Methods 0.000 description 4
ZCSHNCUQKCANBX-UHFFFAOYSA-N lithium diisopropylamide Chemical compound [Li+].CC(C)[N-]C(C)C ZCSHNCUQKCANBX-UHFFFAOYSA-N 0.000 description 4
125000000896 monocarboxylic acid group Chemical group 0.000 description 4
239000012299 nitrogen atmosphere Substances 0.000 description 4
239000003921 oil Substances 0.000 description 4
210000001672 ovary Anatomy 0.000 description 4
125000002971 oxazolyl group Chemical group 0.000 description 4
239000002245 particle Substances 0.000 description 4
239000012071 phase Substances 0.000 description 4
BLTDCIWCFCUQCB-UHFFFAOYSA-N quinoline-3-carboxamide Chemical compound C1=CC=CC2=CC(C(=O)N)=CN=C21 BLTDCIWCFCUQCB-UHFFFAOYSA-N 0.000 description 4
230000009467 reduction Effects 0.000 description 4
238000006722 reduction reaction Methods 0.000 description 4
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 4
125000001113 thiadiazolyl group Chemical group 0.000 description 4
ITMCEJHCFYSIIV-UHFFFAOYSA-M triflate Chemical compound [O-]S(=O)(=O)C(F)(F)F ITMCEJHCFYSIIV-UHFFFAOYSA-M 0.000 description 4
ASOKPJOREAFHNY-UHFFFAOYSA-N 1-Hydroxybenzotriazole Chemical compound C1=CC=C2N(O)N=NC2=C1 ASOKPJOREAFHNY-UHFFFAOYSA-N 0.000 description 3
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