SE453291B - 9-deoxi-9a-metylenisosterer av pgi?712, forfarande for framstellning av dem och en farmaceutisk eller veterinermedicinsk komposition - Google Patents

Info

Publication number

SE453291B

SE453291B SE7900685A SE7900685A SE453291B SE 453291 B SE453291 B SE 453291B SE 7900685 A SE7900685 A SE 7900685A SE 7900685 A SE7900685 A SE 7900685A SE 453291 B SE453291 B SE 453291B

Authority

SE

Sweden

Prior art keywords

deoxy

dihydroxy

prostacycla

methylene

acid

Prior art date

1978-01-26

Links

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• 238000000034 method Methods 0.000 title claims description 88
• 239000000203 mixture Substances 0.000 title claims description 77
• 239000002253 acid Substances 0.000 claims description 381
• 150000001875 compounds Chemical class 0.000 claims description 266
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 264
• -1 C 1 -C 6 alkoxy Chemical group 0.000 claims description 76
• 229910052739 hydrogen Inorganic materials 0.000 claims description 56
• 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 54
• 239000001257 hydrogen Substances 0.000 claims description 52
• 125000006239 protecting group Chemical group 0.000 claims description 40
• 150000002431 hydrogen Chemical class 0.000 claims description 38
• 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 30
• 150000003839 salts Chemical class 0.000 claims description 29
• 150000007513 acids Chemical class 0.000 claims description 21
• 125000004043 oxo group Chemical group O=* 0.000 claims description 21
• 125000005865 C2-C10alkynyl group Chemical group 0.000 claims description 20
• 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 19
• 125000006374 C2-C10 alkenyl group Chemical group 0.000 claims description 18
• 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 17
• 229910052736 halogen Inorganic materials 0.000 claims description 17
• 150000002367 halogens Chemical class 0.000 claims description 17
• 230000008569 process Effects 0.000 claims description 15
• 230000002829 reductive effect Effects 0.000 claims description 15
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 13
• 238000002360 preparation method Methods 0.000 claims description 13
• UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
• 159000000000 sodium salts Chemical class 0.000 claims description 10
• 125000004191 (C1-C6) alkoxy group Chemical group 0.000 claims description 8
• 150000002170 ethers Chemical class 0.000 claims description 7
• 150000002596 lactones Chemical class 0.000 claims description 7
• 125000002619 bicyclic group Chemical group 0.000 claims description 6
• 125000004454 (C1-C6) alkoxycarbonyl group Chemical group 0.000 claims description 5
• 125000004423 acyloxy group Chemical group 0.000 claims description 5
• 238000005935 nucleophilic addition reaction Methods 0.000 claims description 5
• 125000003718 tetrahydrofuranyl group Chemical group 0.000 claims description 5
• 230000029936 alkylation Effects 0.000 claims description 4
• 238000005804 alkylation reaction Methods 0.000 claims description 4
• 125000002883 imidazolyl group Chemical group 0.000 claims description 4
• 125000003545 alkoxy group Chemical group 0.000 claims description 3
• 239000003085 diluting agent Substances 0.000 claims description 3
• 229910052740 iodine Inorganic materials 0.000 claims description 3
• 125000004356 hydroxy functional group Chemical group O* 0.000 claims description 2
• 125000002541 furyl group Chemical group 0.000 claims 3
• RSPISYXLHRIGJD-UHFFFAOYSA-N OOOO Chemical compound OOOO RSPISYXLHRIGJD-UHFFFAOYSA-N 0.000 claims 2
• 238000009833 condensation Methods 0.000 claims 2
• 230000005494 condensation Effects 0.000 claims 2
• 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 claims 2
• 125000005741 alkyl alkenyl group Chemical group 0.000 claims 1
• 235000013405 beer Nutrition 0.000 claims 1
• 125000000468 ketone group Chemical group 0.000 claims 1
• UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 174
• 239000000243 solution Substances 0.000 description 153
• 229910001868 water Inorganic materials 0.000 description 97
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 93
• XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 85
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 85
• IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 82
• YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 78
• CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 72
• WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 71
• 238000006243 chemical reaction Methods 0.000 description 71
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 68
• KAQKFAOMNZTLHT-OZUDYXHBSA-N prostaglandin I2 Chemical compound O1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 KAQKFAOMNZTLHT-OZUDYXHBSA-N 0.000 description 56
• 238000003756 stirring Methods 0.000 description 55
• 150000004702 methyl esters Chemical class 0.000 description 48
• VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 47
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 47
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 46
• 239000002904 solvent Substances 0.000 description 41
• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 38
• 239000012074 organic phase Substances 0.000 description 35
• MUBZPKHOEPUJKR-UHFFFAOYSA-N Oxalic acid Chemical compound OC(=O)C(O)=O MUBZPKHOEPUJKR-UHFFFAOYSA-N 0.000 description 33
• 239000000284 extract Substances 0.000 description 32
• 230000007935 neutral effect Effects 0.000 description 32
• JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 32
• 229960001123 epoprostenol Drugs 0.000 description 31
• 239000011541 reaction mixture Substances 0.000 description 30
• 229910000104 sodium hydride Inorganic materials 0.000 description 30
• ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 29
• 239000003480 eluent Substances 0.000 description 28
• YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 27
• 239000000741 silica gel Substances 0.000 description 26
• 229910002027 silica gel Inorganic materials 0.000 description 26
• 239000011734 sodium Substances 0.000 description 26
• WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 24
• KPUWHANPEXNPJT-UHFFFAOYSA-N disiloxane Chemical class [SiH3]O[SiH3] KPUWHANPEXNPJT-UHFFFAOYSA-N 0.000 description 24
• 239000000047 product Substances 0.000 description 24
• 239000005977 Ethylene Substances 0.000 description 23
• VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 23
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 23
• 150000002576 ketones Chemical group 0.000 description 22
• 101000862089 Clarkia lewisii Glucose-6-phosphate isomerase, cytosolic 1A Proteins 0.000 description 19
• 238000001704 evaporation Methods 0.000 description 19
• QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 18
• 150000002148 esters Chemical class 0.000 description 18
• 230000008020 evaporation Effects 0.000 description 18
• 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 17
• 230000009467 reduction Effects 0.000 description 17
• 238000006722 reduction reaction Methods 0.000 description 17
• 208000007107 Stomach Ulcer Diseases 0.000 description 16
• DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 description 16
• 238000010992 reflux Methods 0.000 description 16
• 235000011121 sodium hydroxide Nutrition 0.000 description 16
• 239000000725 suspension Substances 0.000 description 15
• YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 15
• 229910052784 alkaline earth metal Inorganic materials 0.000 description 14
• 238000004587 chromatography analysis Methods 0.000 description 14
• 150000001241 acetals Chemical class 0.000 description 13
• 229960000583 acetic acid Drugs 0.000 description 13
• 230000003647 oxidation Effects 0.000 description 13
• 238000007254 oxidation reaction Methods 0.000 description 13
• LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 12
• IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
• DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 12
• 150000001299 aldehydes Chemical class 0.000 description 12
• 239000007864 aqueous solution Substances 0.000 description 12
• 229910052681 coesite Inorganic materials 0.000 description 12
• 229910052906 cristobalite Inorganic materials 0.000 description 12
• 230000000694 effects Effects 0.000 description 12
• 230000005764 inhibitory process Effects 0.000 description 12
• 239000012044 organic layer Substances 0.000 description 12
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 12
• HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 12
• 238000010561 standard procedure Methods 0.000 description 12
• 229910052682 stishovite Inorganic materials 0.000 description 12
• 229910052905 tridymite Inorganic materials 0.000 description 12
• 239000012267 brine Substances 0.000 description 11
• 238000001816 cooling Methods 0.000 description 11
• 230000003287 optical effect Effects 0.000 description 11
• 235000006408 oxalic acid Nutrition 0.000 description 11
• 125000001424 substituent group Chemical group 0.000 description 11
• MLOSJPZSZWUDSK-UHFFFAOYSA-N 4-carboxybutyl(triphenyl)phosphanium;bromide Chemical compound [Br-].C=1C=CC=CC=1[P+](C=1C=CC=CC=1)(CCCCC(=O)O)C1=CC=CC=C1 MLOSJPZSZWUDSK-UHFFFAOYSA-N 0.000 description 10
• 241000700159 Rattus Species 0.000 description 10
• 239000002585 base Substances 0.000 description 10
• 238000000605 extraction Methods 0.000 description 10
• UQEAIHBTYFGYIE-UHFFFAOYSA-N hexamethyldisiloxane Chemical compound C[Si](C)(C)O[Si](C)(C)C UQEAIHBTYFGYIE-UHFFFAOYSA-N 0.000 description 10
• LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 10
• 238000000746 purification Methods 0.000 description 10
• ZPVFWPFBNIEHGJ-UHFFFAOYSA-N 2-octanone Chemical compound CCCCCCC(C)=O ZPVFWPFBNIEHGJ-UHFFFAOYSA-N 0.000 description 9
• QOSSAOTZNIDXMA-UHFFFAOYSA-N Dicylcohexylcarbodiimide Chemical compound C1CCCCC1N=C=NC1CCCCC1 QOSSAOTZNIDXMA-UHFFFAOYSA-N 0.000 description 9
• BUDQDWGNQVEFAC-UHFFFAOYSA-N Dihydropyran Chemical compound C1COC=CC1 BUDQDWGNQVEFAC-UHFFFAOYSA-N 0.000 description 9
• 229910010082 LiAlH Inorganic materials 0.000 description 9
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
• 239000003513 alkali Substances 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
• KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 9
• 238000001914 filtration Methods 0.000 description 9
• 201000005917 gastric ulcer Diseases 0.000 description 9
• RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 description 9
• 239000012299 nitrogen atmosphere Substances 0.000 description 9
• TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 9
• 239000012071 phase Substances 0.000 description 9
• 150000003333 secondary alcohols Chemical class 0.000 description 9
• 239000000126 substance Substances 0.000 description 9
• KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 8
• KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 8
• WGLPBDUCMAPZCE-UHFFFAOYSA-N Trioxochromium Chemical compound O=[Cr](=O)=O WGLPBDUCMAPZCE-UHFFFAOYSA-N 0.000 description 8
• 239000012298 atmosphere Substances 0.000 description 8
• 239000000460 chlorine Substances 0.000 description 8
• 150000002084 enol ethers Chemical group 0.000 description 8
• 238000001802 infusion Methods 0.000 description 8
• 239000000376 reactant Substances 0.000 description 8
• 238000007127 saponification reaction Methods 0.000 description 8
• 239000000377 silicon dioxide Substances 0.000 description 8
• YXHKONLOYHBTNS-UHFFFAOYSA-N Diazomethane Chemical compound C=[N+]=[N-] YXHKONLOYHBTNS-UHFFFAOYSA-N 0.000 description 7
• 239000008346 aqueous phase Substances 0.000 description 7
• 238000009835 boiling Methods 0.000 description 7
• 239000000872 buffer Substances 0.000 description 7
• 239000003153 chemical reaction reagent Substances 0.000 description 7
• 238000013375 chromatographic separation Methods 0.000 description 7
• 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 7
• 238000001640 fractional crystallisation Methods 0.000 description 7
• 235000012239 silicon dioxide Nutrition 0.000 description 7
• 229910052708 sodium Inorganic materials 0.000 description 7
• 208000010110 spontaneous platelet aggregation Diseases 0.000 description 7
• 238000010626 work up procedure Methods 0.000 description 7
• 229910004298 SiO 2 Inorganic materials 0.000 description 6
• PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 6
• FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
• 208000025865 Ulcer Diseases 0.000 description 6
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 description 6
• 150000001342 alkaline earth metals Chemical class 0.000 description 6
• 150000001412 amines Chemical class 0.000 description 6
• 150000004292 cyclic ethers Chemical class 0.000 description 6
• YLFBFPXKTIQSSY-UHFFFAOYSA-N dimethoxy(oxo)phosphanium Chemical compound CO[P+](=O)OC YLFBFPXKTIQSSY-UHFFFAOYSA-N 0.000 description 6
• 238000010828 elution Methods 0.000 description 6
• ZKQFHRVKCYFVCN-UHFFFAOYSA-N ethoxyethane;hexane Chemical compound CCOCC.CCCCCC ZKQFHRVKCYFVCN-UHFFFAOYSA-N 0.000 description 6
• 229940117927 ethylene oxide Drugs 0.000 description 6
• 150000004678 hydrides Chemical class 0.000 description 6
• 238000001990 intravenous administration Methods 0.000 description 6
• 239000010410 layer Substances 0.000 description 6
• 239000007788 liquid Substances 0.000 description 6
• 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 6
• 239000002480 mineral oil Substances 0.000 description 6
• 235000010446 mineral oil Nutrition 0.000 description 6
• 229910000027 potassium carbonate Inorganic materials 0.000 description 6
• 150000003815 prostacyclins Chemical class 0.000 description 6
• 150000003180 prostaglandins Chemical class 0.000 description 6
• 229920006395 saturated elastomer Polymers 0.000 description 6
• FPGGTKZVZWFYPV-UHFFFAOYSA-M tetrabutylammonium fluoride Chemical compound [F-].CCCC[N+](CCCC)(CCCC)CCCC FPGGTKZVZWFYPV-UHFFFAOYSA-M 0.000 description 6
• 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 6
• 231100000397 ulcer Toxicity 0.000 description 6
• 229910052725 zinc Inorganic materials 0.000 description 6
• 239000011701 zinc Substances 0.000 description 6
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 5
• 241000282414 Homo sapiens Species 0.000 description 5
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 5
• 230000002378 acidificating effect Effects 0.000 description 5
• 150000001298 alcohols Chemical class 0.000 description 5
• 229910052783 alkali metal Inorganic materials 0.000 description 5
• 125000000217 alkyl group Chemical group 0.000 description 5
• 230000002744 anti-aggregatory effect Effects 0.000 description 5
• 150000004945 aromatic hydrocarbons Chemical class 0.000 description 5
• 239000006185 dispersion Substances 0.000 description 5
• 239000003814 drug Substances 0.000 description 5
• 238000001035 drying Methods 0.000 description 5
• 239000012259 ether extract Substances 0.000 description 5
• 125000001033 ether group Chemical group 0.000 description 5
• 239000011261 inert gas Substances 0.000 description 5
• 239000012442 inert solvent Substances 0.000 description 5
• 239000003921 oil Substances 0.000 description 5
• 235000019198 oils Nutrition 0.000 description 5
• 230000000144 pharmacologic effect Effects 0.000 description 5
• 235000011181 potassium carbonates Nutrition 0.000 description 5
• 238000000926 separation method Methods 0.000 description 5
• 239000012279 sodium borohydride Substances 0.000 description 5
• 229910000033 sodium borohydride Inorganic materials 0.000 description 5
• 150000003509 tertiary alcohols Chemical class 0.000 description 5
• 230000001225 therapeutic effect Effects 0.000 description 5
• HUHXLHLWASNVDB-UHFFFAOYSA-N 2-(oxan-2-yloxy)oxane Chemical compound O1CCCCC1OC1OCCCC1 HUHXLHLWASNVDB-UHFFFAOYSA-N 0.000 description 4
• 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 description 4
• QGZKDVFQNNGYKY-UHFFFAOYSA-N Ammonia Chemical compound N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 4
• NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 4
• XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 4
• OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 4
• XZFRIPGNUQRGPI-WBQKLGIQSA-N Carbaprostacyclin Chemical class C1\C(=C/CCCC(O)=O)C[C@@H]2[C@@H](/C=C/[C@@H](O)CCCCC)[C@H](O)C[C@@H]21 XZFRIPGNUQRGPI-WBQKLGIQSA-N 0.000 description 4
• NOTFZGFABLVTIG-UHFFFAOYSA-N Cyclohexylethyl acetate Chemical compound CC(=O)OCCC1CCCCC1 NOTFZGFABLVTIG-UHFFFAOYSA-N 0.000 description 4
• ZAFNJMIOTHYJRJ-UHFFFAOYSA-N Diisopropyl ether Chemical compound CC(C)OC(C)C ZAFNJMIOTHYJRJ-UHFFFAOYSA-N 0.000 description 4
• XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 4
• VGGSQFUCUMXWEO-UHFFFAOYSA-N Ethene Chemical compound C=C VGGSQFUCUMXWEO-UHFFFAOYSA-N 0.000 description 4
• WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 4
• 241001465754 Metazoa Species 0.000 description 4
• KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-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
• WQDUMFSSJAZKTM-UHFFFAOYSA-N Sodium methoxide Chemical compound [Na+].[O-]C WQDUMFSSJAZKTM-UHFFFAOYSA-N 0.000 description 4
• 150000001338 aliphatic hydrocarbons Chemical class 0.000 description 4
• 150000004808 allyl alcohols Chemical class 0.000 description 4
• QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
• WPYMKLBDIGXBTP-UHFFFAOYSA-N benzoic acid Chemical compound OC(=O)C1=CC=CC=C1 WPYMKLBDIGXBTP-UHFFFAOYSA-N 0.000 description 4
• 229910052791 calcium Inorganic materials 0.000 description 4
• BVKZGUZCCUSVTD-UHFFFAOYSA-N carbonic acid Chemical compound OC(O)=O BVKZGUZCCUSVTD-UHFFFAOYSA-N 0.000 description 4
• 238000006704 dehydrohalogenation reaction Methods 0.000 description 4
• 229960002179 ephedrine Drugs 0.000 description 4
• 238000004128 high performance liquid chromatography Methods 0.000 description 4
• 125000004435 hydrogen atom Chemical group [H]* 0.000 description 4
• 229910052744 lithium Inorganic materials 0.000 description 4
• 229940094443 oxytocics prostaglandins Drugs 0.000 description 4
• 239000012312 sodium hydride Substances 0.000 description 4
• 229910052938 sodium sulfate Inorganic materials 0.000 description 4
• 235000011152 sodium sulphate Nutrition 0.000 description 4
• 150000003555 thioacetals Chemical class 0.000 description 4
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