NO312840B1 - 2-(purin-9-yl)-tetrahydrofuran-3,4-diolderivater, farmasöytisk blanding samt anvendelse og fremstilling derav - Google Patents

Info

Publication number

NO312840B1

NO312840B1 NO19993114A NO993114A NO312840B1 NO 312840 B1 NO312840 B1 NO 312840B1 NO 19993114 A NO19993114 A NO 19993114A NO 993114 A NO993114 A NO 993114A NO 312840 B1 NO312840 B1 NO 312840B1

Authority

NO

Norway

Prior art keywords

diol

tetrazol

tetrahydro

furan

ethyl

Prior art date

1996-12-24

Links

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• 238000002360 preparation method Methods 0.000 title claims description 10
• 239000008194 pharmaceutical composition Substances 0.000 title description 3
• YQUJSBYIKMQCIT-UHFFFAOYSA-N 2-purin-9-yloxolane-3,4-diol Chemical class OC1C(O)COC1N1C2=NC=NC=C2N=C1 YQUJSBYIKMQCIT-UHFFFAOYSA-N 0.000 title 1
• 150000001875 compounds Chemical class 0.000 claims description 267
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 claims description 216
• IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 104
• 239000000203 mixture Substances 0.000 claims description 88
• -1 amino, methoxy, hydroxy Chemical group 0.000 claims description 78
• 229910052757 nitrogen Inorganic materials 0.000 claims description 52
• 238000006243 chemical reaction Methods 0.000 claims description 44
• 229910052736 halogen Inorganic materials 0.000 claims description 38
• 150000002367 halogens Chemical group 0.000 claims description 38
• 238000000034 method Methods 0.000 claims description 35
• 125000000217 alkyl group Chemical group 0.000 claims description 27
• 150000003839 salts Chemical class 0.000 claims description 18
• 239000001257 hydrogen Substances 0.000 claims description 17
• 229910052739 hydrogen Inorganic materials 0.000 claims description 17
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
• 238000011282 treatment Methods 0.000 claims description 16
• 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 claims description 15
• 125000002883 imidazolyl group Chemical group 0.000 claims description 14
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 12
• 239000000460 chlorine Substances 0.000 claims description 9
• 239000011737 fluorine Substances 0.000 claims description 9
• 229910052731 fluorine Inorganic materials 0.000 claims description 9
• GVNVAWHJIKLAGL-UHFFFAOYSA-N 2-(cyclohexen-1-yl)cyclohexan-1-one Chemical compound O=C1CCCCC1C1=CCCCC1 GVNVAWHJIKLAGL-UHFFFAOYSA-N 0.000 claims description 8
• 101150065749 Churc1 gene Proteins 0.000 claims description 8
• 102100038239 Protein Churchill Human genes 0.000 claims description 8
• 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 8
• 125000006552 (C3-C8) cycloalkyl group Chemical group 0.000 claims description 7
• ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims description 7
• 229910052801 chlorine Inorganic materials 0.000 claims description 7
• 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 6
• 208000006673 asthma Diseases 0.000 claims description 6
• 238000010511 deprotection reaction Methods 0.000 claims description 6
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 6
• 230000008569 process Effects 0.000 claims description 6
• 125000004076 pyridyl group Chemical group 0.000 claims description 6
• 239000012453 solvate Substances 0.000 claims description 6
• 125000004575 3-pyrrolidinyl group Chemical group [H]N1C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
• 229910006074 SO2NH2 Inorganic materials 0.000 claims description 5
• 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 5
• 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 claims description 5
• 239000003814 drug Substances 0.000 claims description 5
• 208000027866 inflammatory disease Diseases 0.000 claims description 5
• LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 5
• 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 claims description 4
• 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 claims description 4
• 125000003118 aryl group Chemical group 0.000 claims description 4
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 4
• 150000002431 hydrogen Chemical class 0.000 claims description 4
• VZCYOOQTPOCHFL-UPHRSURJSA-N maleic acid Chemical compound OC(=O)\C=C/C(O)=O VZCYOOQTPOCHFL-UPHRSURJSA-N 0.000 claims description 4
• 238000004519 manufacturing process Methods 0.000 claims description 4
• 125000005322 morpholin-1-yl group Chemical group 0.000 claims description 4
• 229910052760 oxygen Inorganic materials 0.000 claims description 4
• VZCYOOQTPOCHFL-UHFFFAOYSA-N trans-butenedioic acid Natural products OC(=O)C=CC(O)=O VZCYOOQTPOCHFL-UHFFFAOYSA-N 0.000 claims description 4
• 239000000969 carrier Substances 0.000 claims description 3
• 125000004483 piperidin-3-yl group Chemical group N1CC(CCC1)* 0.000 claims description 3
• 125000004482 piperidin-4-yl group Chemical group N1CCC(CC1)* 0.000 claims description 3
• 229910052717 sulfur Inorganic materials 0.000 claims description 3
• 125000004214 1-pyrrolidinyl group Chemical group [H]C1([H])N(*)C([H])([H])C([H])([H])C1([H])[H] 0.000 claims description 2
• 125000000753 cycloalkyl group Chemical group 0.000 claims description 2
• 239000003085 diluting agent Substances 0.000 claims description 2
• 229940079593 drug Drugs 0.000 claims description 2
• 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 2
• 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 2
• PXGOKWXKJXAPGV-UHFFFAOYSA-N Fluorine Chemical compound FF PXGOKWXKJXAPGV-UHFFFAOYSA-N 0.000 claims 3
• LCFFJOYIXJKWRM-UHFFFAOYSA-N 2-(2-ethyltetrazol-5-yl)oxolane-3,4-diol Chemical compound CCN1N=NC(C2C(C(O)CO2)O)=N1 LCFFJOYIXJKWRM-UHFFFAOYSA-N 0.000 claims 2
• SSYDTHANSGMJTP-UHFFFAOYSA-N oxolane-3,4-diol Chemical compound OC1COCC1O SSYDTHANSGMJTP-UHFFFAOYSA-N 0.000 claims 2
• 125000004545 purin-9-yl group Chemical group N1=CN=C2N(C=NC2=C1)* 0.000 claims 2
• CCYUSUQOSHABQD-OVDFTCDZSA-N (2r,3r,4s,5r)-2-[6-(2,2-diphenylethylamino)-2-(2-morpholin-4-ylethylamino)purin-9-yl]-5-(2-ethyltetrazol-5-yl)oxolane-3,4-diol Chemical compound CCN1N=NC([C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC(NCCN4CCOCC4)=NC(NCC(C=4C=CC=CC=4)C=4C=CC=CC=4)=C3N=C2)O)=N1 CCYUSUQOSHABQD-OVDFTCDZSA-N 0.000 claims 1
• NTGVVIJCALQADM-MMSSMPOCSA-N (2r,3r,4s,5r)-2-[6-(2,2-diphenylethylamino)-2-(pyrrolidin-3-ylamino)purin-9-yl]-5-(2-ethyltetrazol-5-yl)oxolane-3,4-diol Chemical compound CCN1N=NC([C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC(NC4CNCC4)=NC(NCC(C=4C=CC=CC=4)C=4C=CC=CC=4)=C3N=C2)O)=N1 NTGVVIJCALQADM-MMSSMPOCSA-N 0.000 claims 1
• CMJVPOARTDAFBV-RQXXJAGISA-N (2r,3r,4s,5r)-2-[6-(3,3-dimethylbutylamino)-2-[2-(1-methylimidazol-4-yl)ethylamino]purin-9-yl]-5-(2-ethyltetrazol-5-yl)oxolane-3,4-diol Chemical compound CCN1N=NC([C@@H]2[C@H]([C@@H](O)[C@@H](O2)N2C3=NC(NCCC=4N=CN(C)C=4)=NC(NCCC(C)(C)C)=C3N=C2)O)=N1 CMJVPOARTDAFBV-RQXXJAGISA-N 0.000 claims 1
• VLFNMYSVSZTCML-RQXXJAGISA-N (2r,3r,4s,5r)-2-[6-amino-2-[2-(3,4-dimethoxyphenyl)ethylamino]purin-9-yl]-5-(2-propan-2-yltetrazol-5-yl)oxolane-3,4-diol Chemical compound C1=C(OC)C(OC)=CC=C1CCNC1=NC(N)=C(N=CN2[C@H]3[C@@H]([C@H](O)[C@H](O3)C3=NN(N=N3)C(C)C)O)C2=N1 VLFNMYSVSZTCML-RQXXJAGISA-N 0.000 claims 1
• XYHKLPLXXLUDKV-RQXXJAGISA-N (2r,3s,4r,5r)-2-(2-methyltetrazol-5-yl)-5-[6-(pentan-3-ylamino)-2-(2-pyridin-2-ylethylamino)purin-9-yl]oxolane-3,4-diol Chemical compound N=1C=2N([C@H]3[C@@H]([C@H](O)[C@H](O3)C3=NN(C)N=N3)O)C=NC=2C(NC(CC)CC)=NC=1NCCC1=CC=CC=N1 XYHKLPLXXLUDKV-RQXXJAGISA-N 0.000 claims 1
• AWKWFPJUWHYSGJ-GRXQJBFDSA-N (2r,3s,4r,5r)-2-(2-methyltetrazol-5-yl)-5-[6-(pentan-3-ylamino)-2-(2-pyrrolidin-1-ylethylamino)purin-9-yl]oxolane-3,4-diol Chemical compound N=1C=2N([C@H]3[C@@H]([C@H](O)[C@H](O3)C3=NN(C)N=N3)O)C=NC=2C(NC(CC)CC)=NC=1NCCN1CCCC1 AWKWFPJUWHYSGJ-GRXQJBFDSA-N 0.000 claims 1
• HIUJHNNCBNJKGX-UHFFFAOYSA-N 2-(2-methyltetrazol-5-yl)oxolane-3,4-diol Chemical compound CN1N=NC(C2C(C(O)CO2)O)=N1 HIUJHNNCBNJKGX-UHFFFAOYSA-N 0.000 claims 1
• BKJJATGKMNJRBW-UHFFFAOYSA-N 2-(2-propan-2-yltetrazol-5-yl)oxolane-3,4-diol Chemical compound CC(C)N1N=NC(C2C(C(O)CO2)O)=N1 BKJJATGKMNJRBW-UHFFFAOYSA-N 0.000 claims 1
• 125000004204 2-methoxyphenyl group Chemical group [H]C1=C([H])C(*)=C(OC([H])([H])[H])C([H])=C1[H] 0.000 claims 1
• 125000000031 ethylamino group Chemical group [H]C([H])([H])C([H])([H])N([H])[*] 0.000 claims 1
• 125000004435 hydrogen atom Chemical group [H]* 0.000 claims 1
• 239000008177 pharmaceutical agent Substances 0.000 claims 1
• 125000000565 sulfonamide group Chemical group 0.000 claims 1
• 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 221
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 195
• 239000007787 solid Substances 0.000 description 135
• 239000000543 intermediate Substances 0.000 description 116
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 105
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 103
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 100
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 79
• 238000004108 freeze drying Methods 0.000 description 76
• 239000011541 reaction mixture Substances 0.000 description 74
• 239000000243 solution Substances 0.000 description 70
• 239000002904 solvent Substances 0.000 description 70
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 59
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 48
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 48
• 229960004592 isopropanol Drugs 0.000 description 48
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 46
• QTBSBXVTEAMEQO-UHFFFAOYSA-N acetic acid Substances CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 43
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
• XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 38
• 238000004809 thin layer chromatography Methods 0.000 description 35
• BDAGIHXWWSANSR-UHFFFAOYSA-M Formate Chemical compound [O-]C=O BDAGIHXWWSANSR-UHFFFAOYSA-M 0.000 description 34
• 239000000047 product Substances 0.000 description 34
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 30
• JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 24
• 239000003921 oil Substances 0.000 description 24
• 235000019198 oils Nutrition 0.000 description 24
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 21
• 239000006260 foam Substances 0.000 description 21
• 238000002953 preparative HPLC Methods 0.000 description 21
• OIRDTQYFTABQOQ-KQYNXXCUSA-N adenosine Chemical compound C1=NC=2C(N)=NC=NC=2N1[C@@H]1O[C@H](CO)[C@@H](O)[C@H]1O OIRDTQYFTABQOQ-KQYNXXCUSA-N 0.000 description 20
• 239000011928 denatured alcohol Substances 0.000 description 20
• 238000010438 heat treatment Methods 0.000 description 20
• 239000010410 layer Substances 0.000 description 20
• 239000000377 silicon dioxide Substances 0.000 description 20
• STVVMTBJNDTZBF-VIFPVBQESA-N L-phenylalaninol Chemical compound OC[C@@H](N)CC1=CC=CC=C1 STVVMTBJNDTZBF-VIFPVBQESA-N 0.000 description 19
• 238000004440 column chromatography Methods 0.000 description 19
• 238000004128 high performance liquid chromatography Methods 0.000 description 19
• 238000003756 stirring Methods 0.000 description 19
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 18
• FHQDWPCFSJMNCT-UHFFFAOYSA-N N(tele)-methylhistamine Chemical compound CN1C=NC(CCN)=C1 FHQDWPCFSJMNCT-UHFFFAOYSA-N 0.000 description 18
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 18
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 17
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical class OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 17
• 210000000265 leukocyte Anatomy 0.000 description 16
• 229910004298 SiO 2 Inorganic materials 0.000 description 15
• 238000001819 mass spectrum Methods 0.000 description 15
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 14
• BHHGXPLMPWCGHP-UHFFFAOYSA-N Phenethylamine Chemical compound NCCC1=CC=CC=C1 BHHGXPLMPWCGHP-UHFFFAOYSA-N 0.000 description 14
• NISGSNTVMOOSJQ-UHFFFAOYSA-N cyclopentanamine Chemical compound NC1CCCC1 NISGSNTVMOOSJQ-UHFFFAOYSA-N 0.000 description 14
• 239000000706 filtrate Substances 0.000 description 14
• LQLOGZQVKUNBRX-UHFFFAOYSA-N (3-iodophenyl)methanamine Chemical compound NCC1=CC=CC(I)=C1 LQLOGZQVKUNBRX-UHFFFAOYSA-N 0.000 description 13
• CJNRGSHEMCMUOE-UHFFFAOYSA-N 2-piperidin-1-ylethanamine Chemical compound NCCN1CCCCC1 CJNRGSHEMCMUOE-UHFFFAOYSA-N 0.000 description 13
• VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 13
• 238000002414 normal-phase solid-phase extraction Methods 0.000 description 13
• PQPFFKCJENSZKL-UHFFFAOYSA-N pentan-3-amine Chemical compound CCC(N)CC PQPFFKCJENSZKL-UHFFFAOYSA-N 0.000 description 13
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 12
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 12
• 239000012458 free base Substances 0.000 description 12
• BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 description 12
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 11
• 235000019441 ethanol Nutrition 0.000 description 11
• 108020003175 receptors Proteins 0.000 description 11
• 102000005962 receptors Human genes 0.000 description 11
• RXMTUVIKZRXSSM-UHFFFAOYSA-N 2,2-diphenylethanamine Chemical compound C=1C=CC=CC=1C(CN)C1=CC=CC=C1 RXMTUVIKZRXSSM-UHFFFAOYSA-N 0.000 description 10
• 239000002126 C01EB10 - Adenosine Substances 0.000 description 10
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 10
• DTQVDTLACAAQTR-UHFFFAOYSA-M Trifluoroacetate Chemical compound [O-]C(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-M 0.000 description 10
• 229960005305 adenosine Drugs 0.000 description 10
• 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 10
• 230000000694 effects Effects 0.000 description 10
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
• 239000007795 chemical reaction product Substances 0.000 description 9
• 239000003795 chemical substances by application Substances 0.000 description 9
• VKIRRGRTJUUZHS-UHFFFAOYSA-N cyclohexane-1,4-diamine Chemical compound NC1CCC(N)CC1 VKIRRGRTJUUZHS-UHFFFAOYSA-N 0.000 description 9
• 201000010099 disease Diseases 0.000 description 9
• RWIVICVCHVMHMU-UHFFFAOYSA-N n-aminoethylmorpholine Chemical compound NCCN1CCOCC1 RWIVICVCHVMHMU-UHFFFAOYSA-N 0.000 description 9
• 239000012044 organic layer Substances 0.000 description 9
• 239000000843 powder Substances 0.000 description 9
• 239000000556 agonist Substances 0.000 description 8
• 229910021529 ammonia Inorganic materials 0.000 description 8
• WGQKYBSKWIADBV-UHFFFAOYSA-N benzylamine Chemical compound NCC1=CC=CC=C1 WGQKYBSKWIADBV-UHFFFAOYSA-N 0.000 description 8
• 239000000284 extract Substances 0.000 description 8
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 8
• 235000017557 sodium bicarbonate Nutrition 0.000 description 8
• 239000000725 suspension Substances 0.000 description 8
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 8
• FTVLMFQEYACZNP-UHFFFAOYSA-N trimethylsilyl trifluoromethanesulfonate Chemical compound C[Si](C)(C)OS(=O)(=O)C(F)(F)F FTVLMFQEYACZNP-UHFFFAOYSA-N 0.000 description 8
• PYMYPHUHKUWMLA-LMVFSUKVSA-N Ribose Natural products OC[C@@H](O)[C@@H](O)[C@@H](O)C=O PYMYPHUHKUWMLA-LMVFSUKVSA-N 0.000 description 7
• 239000012267 brine Substances 0.000 description 7
• 239000002244 precipitate Substances 0.000 description 7
• 238000010992 reflux Methods 0.000 description 7
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 7
• ANOUKFYBOAKOIR-UHFFFAOYSA-N 3,4-dimethoxyphenylethylamine Chemical compound COC1=CC=C(CCN)C=C1OC ANOUKFYBOAKOIR-UHFFFAOYSA-N 0.000 description 6
• 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
• YCKRFDGAMUMZLT-UHFFFAOYSA-N Fluorine atom Chemical compound [F] YCKRFDGAMUMZLT-UHFFFAOYSA-N 0.000 description 6
• ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 6
• 239000002253 acid Substances 0.000 description 6
• 239000008346 aqueous phase Substances 0.000 description 6
• 239000002585 base Substances 0.000 description 6
• 238000004587 chromatography analysis Methods 0.000 description 6
• 210000003979 eosinophil Anatomy 0.000 description 6
• 235000019253 formic acid Nutrition 0.000 description 6
• 239000008241 heterogeneous mixture Substances 0.000 description 6
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