DK149892B - Analogifremgangsmaade til fremstilling af 5-halogenpyrimidin-2-oner eller farmaceutisk acceptable salte deraf - Google Patents

Analogifremgangsmaade til fremstilling af 5-halogenpyrimidin-2-oner eller farmaceutisk acceptable salte deraf Download PDF

Info

Publication number: DK149892B
Authority: DK; Denmark
Prior art keywords: group; alk; het; ring; compound
Prior art date: 1980-01-07

Application number

DK003281AA

Other languages

Danish (da)

English (en)

Other versions

DK3281A (da

Inventor

Mikkel Josef Gacek

Kjell Undheim

Original Assignee

Nyegaard & Co As

Priority date (The priority date 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 date listed.)

1980-01-07

Filing date

1981-01-06

Publication date

1986-10-20

1981-01-06 Application filed by Nyegaard & Co As filed Critical Nyegaard & Co As

1981-07-08 Publication of DK3281A publication Critical patent/DK3281A/da

1986-10-20 Publication of DK149892B publication Critical patent/DK149892B/da

Links

150000003839 salts Chemical class 0.000 title claims abstract description 20
238000000034 method Methods 0.000 title claims description 20
238000002360 preparation method Methods 0.000 title claims description 4
150000001875 compounds Chemical class 0.000 claims abstract description 58
229910052757 nitrogen Inorganic materials 0.000 claims abstract description 24
125000000623 heterocyclic group Chemical group 0.000 claims abstract description 14
125000005843 halogen group Chemical group 0.000 claims abstract description 9
125000003118 aryl group Chemical group 0.000 claims abstract description 7
125000005842 heteroatom Chemical group 0.000 claims abstract description 7
125000002887 hydroxy group Chemical group [H]O* 0.000 claims abstract description 6
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims abstract description 6
125000001424 substituent group Chemical group 0.000 claims abstract description 6
125000004043 oxo group Chemical group O=* 0.000 claims abstract description 5
125000001931 aliphatic group Chemical group 0.000 claims abstract description 4
125000004435 hydrogen atom Chemical group [H]* 0.000 claims abstract description 4
229920006395 saturated elastomer Polymers 0.000 claims abstract 6
125000004178 (C1-C4) alkyl group Chemical group 0.000 claims abstract 4
125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims abstract 2
125000006615 aromatic heterocyclic group Chemical group 0.000 claims abstract 2
125000001183 hydrocarbyl group Chemical group 0.000 claims abstract 2
125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims abstract 2
229910052760 oxygen Inorganic materials 0.000 claims abstract 2
229910052717 sulfur Inorganic materials 0.000 claims abstract 2
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 claims description 38
DHKHKXVYLBGOIT-UHFFFAOYSA-N acetaldehyde Diethyl Acetal Natural products CCOC(C)OCC DHKHKXVYLBGOIT-UHFFFAOYSA-N 0.000 claims description 20
125000002777 acetyl group Chemical class [H]C([H])([H])C(*)=O 0.000 claims description 19
230000002378 acidificating effect Effects 0.000 claims description 5
125000004429 atom Chemical group 0.000 claims description 4
239000001257 hydrogen Substances 0.000 claims description 3
229910052739 hydrogen Inorganic materials 0.000 claims description 3
125000004433 nitrogen atom Chemical group N* 0.000 claims description 3
150000002148 esters Chemical class 0.000 claims description 2
HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical group C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims 1
125000003158 alcohol group Chemical group 0.000 claims 1
125000005236 alkanoylamino group Chemical group 0.000 claims 1
238000007363 ring formation reaction Methods 0.000 claims 1
230000002159 abnormal effect Effects 0.000 abstract description 15
230000031864 metaphase Effects 0.000 abstract description 9
230000004663 cell proliferation Effects 0.000 abstract description 6
238000006798 ring closing metathesis reaction Methods 0.000 abstract description 5
125000002837 carbocyclic group Chemical group 0.000 abstract description 3
230000022131 cell cycle Effects 0.000 abstract description 3
125000000714 pyrimidinyl group Chemical group 0.000 abstract description 3
229940127089 cytotoxic agent Drugs 0.000 abstract description 2
239000002254 cytotoxic agent Substances 0.000 abstract description 2
125000004442 acylamino group Chemical group 0.000 abstract 1
230000029936 alkylation Effects 0.000 abstract 1
238000005804 alkylation reaction Methods 0.000 abstract 1
230000026030 halogenation Effects 0.000 abstract 1
238000005658 halogenation reaction Methods 0.000 abstract 1
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 128
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 125
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 63
239000007787 solid Substances 0.000 description 56
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 54
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 45
235000019439 ethyl acetate Nutrition 0.000 description 42
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 38
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 30
239000011541 reaction mixture Substances 0.000 description 29
239000000203 mixture Substances 0.000 description 27
239000013078 crystal Substances 0.000 description 26
210000004027 cell Anatomy 0.000 description 25
239000000725 suspension Substances 0.000 description 25
239000000243 solution Substances 0.000 description 24
VTGOHKSTWXHQJK-UHFFFAOYSA-N pyrimidin-2-ol Chemical compound OC1=NC=CC=N1 VTGOHKSTWXHQJK-UHFFFAOYSA-N 0.000 description 23
OCSYCDVQABSEPJ-UHFFFAOYSA-N 5-chloro-1h-pyrimidin-2-one Chemical compound OC1=NC=C(Cl)C=N1 OCSYCDVQABSEPJ-UHFFFAOYSA-N 0.000 description 21
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 21
YCIPQJTZJGUXND-UHFFFAOYSA-N Aglaia odorata Alkaloid Natural products C1=CC(OC)=CC=C1C1(C(C=2C(=O)N3CCCC3=NC=22)C=3C=CC=CC=3)C2(O)C2=C(OC)C=C(OC)C=C2O1 YCIPQJTZJGUXND-UHFFFAOYSA-N 0.000 description 20
239000012071 phase Substances 0.000 description 15
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
238000004440 column chromatography Methods 0.000 description 12
239000003814 drug Substances 0.000 description 11
229940079593 drug Drugs 0.000 description 11
-1 methyl Chemical compound 0.000 description 11
HEMHJVSKTPXQMS-UHFFFAOYSA-M sodium hydroxide Inorganic materials [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 11
KXHPPCXNWTUNSB-UHFFFAOYSA-M benzyl(trimethyl)azanium;chloride Chemical compound [Cl-].C[N+](C)(C)CC1=CC=CC=C1 KXHPPCXNWTUNSB-UHFFFAOYSA-M 0.000 description 10
239000006260 foam Substances 0.000 description 10
KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 9
CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 9
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 9
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
238000006243 chemical reaction Methods 0.000 description 8
239000006071 cream Substances 0.000 description 8
239000003208 petroleum Substances 0.000 description 8
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 6
230000018199 S phase Effects 0.000 description 6
YTPLMLYBLZKORZ-UHFFFAOYSA-N Thiophene Chemical compound C=1C=CSC=1 YTPLMLYBLZKORZ-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 6
KRKNYBCHXYNGOX-UHFFFAOYSA-N citric acid Chemical compound OC(=O)CC(O)(C(O)=O)CC(O)=O KRKNYBCHXYNGOX-UHFFFAOYSA-N 0.000 description 6
230000000694 effects Effects 0.000 description 6
239000000706 filtrate Substances 0.000 description 6
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 6
230000011278 mitosis Effects 0.000 description 6
125000000217 alkyl group Chemical group 0.000 description 5
239000012267 brine Substances 0.000 description 5
GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 5
230000032823 cell division Effects 0.000 description 5
238000011161 development Methods 0.000 description 5
239000000284 extract Substances 0.000 description 5
239000007788 liquid Substances 0.000 description 5
238000010992 reflux Methods 0.000 description 5
HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical compound O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
230000006820 DNA synthesis Effects 0.000 description 4
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 4
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 4
238000005481 NMR spectroscopy Methods 0.000 description 4
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 4
QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 4
125000003277 amino group Chemical group 0.000 description 4
239000002585 base Substances 0.000 description 4
229910052794 bromium Inorganic materials 0.000 description 4
229910052799 carbon Inorganic materials 0.000 description 4
125000004432 carbon atom Chemical group C* 0.000 description 4
239000000460 chlorine Substances 0.000 description 4
231100000433 cytotoxic Toxicity 0.000 description 4
230000001472 cytotoxic effect Effects 0.000 description 4
238000010828 elution Methods 0.000 description 4
KBAODSJOEVGXBY-UHFFFAOYSA-N ethyl 4-(bromomethyl)-2-methyl-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C=1SC(C)=NC=1CBr KBAODSJOEVGXBY-UHFFFAOYSA-N 0.000 description 4
238000002474 experimental method Methods 0.000 description 4
125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 4
239000012074 organic phase Substances 0.000 description 4
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 4
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 4
239000002244 precipitate Substances 0.000 description 4
NDVLTYZPCACLMA-UHFFFAOYSA-N silver oxide Chemical compound [O-2].[Ag+].[Ag+] NDVLTYZPCACLMA-UHFFFAOYSA-N 0.000 description 4
VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 4
ZPHGMBGIFODUMF-UHFFFAOYSA-N thiophen-2-ylmethanol Chemical compound OCC1=CC=CS1 ZPHGMBGIFODUMF-UHFFFAOYSA-N 0.000 description 4
FUOHKPSBGLXIRL-UHFFFAOYSA-N 2-(chloromethyl)thiophene Chemical compound ClCC1=CC=CS1 FUOHKPSBGLXIRL-UHFFFAOYSA-N 0.000 description 3
GRLWQORZOWPFCM-UHFFFAOYSA-N 5-chloro-1h-pyrimidin-2-one;hydrochloride Chemical compound Cl.ClC=1C=NC(=O)NC=1 GRLWQORZOWPFCM-UHFFFAOYSA-N 0.000 description 3
WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
241000400611 Eucalyptus deanei Species 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N Furan Chemical compound C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
229910052784 alkaline earth metal Inorganic materials 0.000 description 3
PNEYBMLMFCGWSK-UHFFFAOYSA-N aluminium oxide Inorganic materials [O-2].[O-2].[O-2].[Al+3].[Al+3] PNEYBMLMFCGWSK-UHFFFAOYSA-N 0.000 description 3
150000003863 ammonium salts Chemical class 0.000 description 3
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 3
239000003795 chemical substances by application Substances 0.000 description 3
238000004587 chromatography analysis Methods 0.000 description 3
238000002425 crystallisation Methods 0.000 description 3
230000008025 crystallization Effects 0.000 description 3
BLBVWRXRVAAJCG-UHFFFAOYSA-N ethyl 2-(bromomethyl)-4-methyl-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C=1SC(CBr)=NC=1C BLBVWRXRVAAJCG-UHFFFAOYSA-N 0.000 description 3
239000000463 material Substances 0.000 description 3
230000000394 mitotic effect Effects 0.000 description 3
239000003921 oil Substances 0.000 description 3
235000019198 oils Nutrition 0.000 description 3
230000002829 reductive effect Effects 0.000 description 3
239000011734 sodium Substances 0.000 description 3
239000002904 solvent Substances 0.000 description 3
238000003756 stirring Methods 0.000 description 3
238000012360 testing method Methods 0.000 description 3
229930192474 thiophene Natural products 0.000 description 3
238000001665 trituration Methods 0.000 description 3
UAQJEIWAMCLVTE-UHFFFAOYSA-N (3-methylthiophen-2-yl)methanol Chemical compound CC=1C=CSC=1CO UAQJEIWAMCLVTE-UHFFFAOYSA-N 0.000 description 2
DBRSLMCLMMFHEF-UHFFFAOYSA-N (5-bromothiophen-2-yl)methanol Chemical compound OCC1=CC=C(Br)S1 DBRSLMCLMMFHEF-UHFFFAOYSA-N 0.000 description 2
YFUJJGBBAUDCDX-UHFFFAOYSA-N 1-(3-bromo-2-hydroxypropyl)-5-chloropyrimidin-2-one Chemical compound BrCC(O)CN1C=C(Cl)C=NC1=O YFUJJGBBAUDCDX-UHFFFAOYSA-N 0.000 description 2
KMJUNPBVHKPUPN-UHFFFAOYSA-N 1-[(5-bromothiophen-2-yl)methyl]-5-chloropyrimidin-2-one Chemical compound C1=C(Cl)C=NC(=O)N1CC1=CC=C(Br)S1 KMJUNPBVHKPUPN-UHFFFAOYSA-N 0.000 description 2
125000000175 2-thienyl group Chemical group S1C([*])=C([H])C([H])=C1[H] 0.000 description 2
VDQDBLVLPNTJSS-UHFFFAOYSA-N 4-(chloromethyl)-n-trityl-1,3-thiazol-2-amine Chemical compound ClCC1=CSC(NC(C=2C=CC=CC=2)(C=2C=CC=CC=2)C=2C=CC=CC=2)=N1 VDQDBLVLPNTJSS-UHFFFAOYSA-N 0.000 description 2
MXDXAOQUIXLTBW-UHFFFAOYSA-N 4-methylbenzenesulfonic acid;2-thiophen-2-ylethanol Chemical compound OCCC1=CC=CS1.CC1=CC=C(S(O)(=O)=O)C=C1 MXDXAOQUIXLTBW-UHFFFAOYSA-N 0.000 description 2
NDCXNAAPTYFDOM-UHFFFAOYSA-N 5-chloro-1-(2-thiophen-2-ylethyl)pyrimidin-2-one Chemical compound C1=C(Cl)C=NC(=O)N1CCC1=CC=CS1 NDCXNAAPTYFDOM-UHFFFAOYSA-N 0.000 description 2
JJORBTDLCYWNSG-UHFFFAOYSA-N 5-chloro-1-(oxiran-2-ylmethyl)pyrimidin-2-one Chemical compound C1=C(Cl)C=NC(=O)N1CC1OC1 JJORBTDLCYWNSG-UHFFFAOYSA-N 0.000 description 2
YZOKITXZQWCTGN-UHFFFAOYSA-N 5-chloro-1-[(3-methylthiophen-2-yl)methyl]pyrimidin-2-one Chemical compound C1=CSC(CN2C(N=CC(Cl)=C2)=O)=C1C YZOKITXZQWCTGN-UHFFFAOYSA-N 0.000 description 2
HLXKPNAHHFWHON-UHFFFAOYSA-N 5-chloro-4-hydrazinyl-6-methyl-1-(thiophen-2-ylmethyl)pyrimidin-2-one Chemical compound CC1=C(Cl)C(NN)=NC(=O)N1CC1=CC=CS1 HLXKPNAHHFWHON-UHFFFAOYSA-N 0.000 description 2
SFWCFDOIDFKHKC-UHFFFAOYSA-N 5-chloro-6-methyl-1-(thiophen-2-ylmethyl)pyrimidin-2-one Chemical compound CC1=C(Cl)C=NC(=O)N1CC1=CC=CS1 SFWCFDOIDFKHKC-UHFFFAOYSA-N 0.000 description 2
PTXQXRKOPZRLGT-UHFFFAOYSA-N 5-chloro-6-methyl-4-methylsulfanyl-1-(thiophen-2-ylmethyl)pyrimidin-2-one Chemical compound CC1=C(Cl)C(SC)=NC(=O)N1CC1=CC=CS1 PTXQXRKOPZRLGT-UHFFFAOYSA-N 0.000 description 2
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 2
239000004342 Benzoyl peroxide Substances 0.000 description 2
OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 2
OYPRJOBELJOOCE-UHFFFAOYSA-N Calcium Chemical compound [Ca] OYPRJOBELJOOCE-UHFFFAOYSA-N 0.000 description 2
UHDGCWIWMRVCDJ-CCXZUQQUSA-N Cytarabine Chemical compound O=C1N=C(N)C=CN1[C@H]1[C@@H](O)[C@H](O)[C@@H](CO)O1 UHDGCWIWMRVCDJ-CCXZUQQUSA-N 0.000 description 2
FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 description 2
230000010337 G2 phase Effects 0.000 description 2
OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 description 2
VSNHCAURESNICA-UHFFFAOYSA-N Hydroxyurea Chemical compound NC(=O)NO VSNHCAURESNICA-UHFFFAOYSA-N 0.000 description 2
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
206010028980 Neoplasm Diseases 0.000 description 2
235000019502 Orange oil Nutrition 0.000 description 2
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 2
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
KAESVJOAVNADME-UHFFFAOYSA-N Pyrrole Chemical compound C=1C=CNC=1 KAESVJOAVNADME-UHFFFAOYSA-N 0.000 description 2
FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 description 2
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 2
XSQUKJJJFZCRTK-UHFFFAOYSA-N Urea Chemical compound NC(N)=O XSQUKJJJFZCRTK-UHFFFAOYSA-N 0.000 description 2
150000007513 acids Chemical class 0.000 description 2
239000004480 active ingredient Substances 0.000 description 2
150000001342 alkaline earth metals Chemical class 0.000 description 2
125000003545 alkoxy group Chemical group 0.000 description 2
230000000340 anti-metabolite Effects 0.000 description 2
229940100197 antimetabolite Drugs 0.000 description 2
239000002256 antimetabolite Substances 0.000 description 2
235000019400 benzoyl peroxide Nutrition 0.000 description 2
239000011575 calcium Substances 0.000 description 2
229910052791 calcium Inorganic materials 0.000 description 2
201000011510 cancer Diseases 0.000 description 2
239000003153 chemical reaction reagent Substances 0.000 description 2
229910052801 chlorine Inorganic materials 0.000 description 2
238000001816 cooling Methods 0.000 description 2
BXOIIRQIGYJTTB-UHFFFAOYSA-N ethyl 2,4-dimethyl-1,3-thiazole-5-carboxylate Chemical compound CCOC(=O)C=1SC(C)=NC=1C BXOIIRQIGYJTTB-UHFFFAOYSA-N 0.000 description 2
SFFBELXPCFGXAY-UHFFFAOYSA-N ethyl 2-[(5-chloro-2-oxopyrimidin-1-yl)methyl]-4-methyl-1,3-thiazole-5-carboxylate Chemical compound CC1=C(C(=O)OCC)SC(CN2C(N=CC(Cl)=C2)=O)=N1 SFFBELXPCFGXAY-UHFFFAOYSA-N 0.000 description 2
238000001704 evaporation Methods 0.000 description 2
230000008020 evaporation Effects 0.000 description 2
125000002541 furyl group Chemical group 0.000 description 2
229960001330 hydroxycarbamide Drugs 0.000 description 2
230000002401 inhibitory effect Effects 0.000 description 2
229910052500 inorganic mineral Inorganic materials 0.000 description 2
239000010410 layer Substances 0.000 description 2
239000011707 mineral Substances 0.000 description 2
235000010755 mineral Nutrition 0.000 description 2
239000010502 orange oil Substances 0.000 description 2
150000007524 organic acids Chemical class 0.000 description 2
235000005985 organic acids Nutrition 0.000 description 2
VLTRZXGMWDSKGL-UHFFFAOYSA-N perchloric acid Chemical compound OCl(=O)(=O)=O VLTRZXGMWDSKGL-UHFFFAOYSA-N 0.000 description 2
239000002798 polar solvent Substances 0.000 description 2
239000011591 potassium Substances 0.000 description 2
229910052700 potassium Inorganic materials 0.000 description 2
229910000027 potassium carbonate Inorganic materials 0.000 description 2
239000000047 product Substances 0.000 description 2
125000004076 pyridyl group Chemical group 0.000 description 2
QIEQDFYXVYQLLU-UHFFFAOYSA-N pyrimidin-4-ylhydrazine Chemical compound NNC1=CC=NC=N1 QIEQDFYXVYQLLU-UHFFFAOYSA-N 0.000 description 2
229910001923 silver oxide Inorganic materials 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
229910000030 sodium bicarbonate Inorganic materials 0.000 description 2
235000017557 sodium bicarbonate Nutrition 0.000 description 2
239000012279 sodium borohydride Substances 0.000 description 2
229910000033 sodium borohydride Inorganic materials 0.000 description 2
230000001360 synchronised effect Effects 0.000 description 2
239000011975 tartaric acid Substances 0.000 description 2
235000002906 tartaric acid Nutrition 0.000 description 2
125000000335 thiazolyl group Chemical group 0.000 description 2
125000001544 thienyl group Chemical group 0.000 description 2
JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 2
BHGUSWOZYFZTMG-UHFFFAOYSA-N (1-methylpyrrol-2-yl)methanol Chemical compound CN1C=CC=C1CO BHGUSWOZYFZTMG-UHFFFAOYSA-N 0.000 description 1
NWZSZGALRFJKBT-KNIFDHDWSA-N (2s)-2,6-diaminohexanoic acid;(2s)-2-hydroxybutanedioic acid Chemical compound OC(=O)[C@@H](O)CC(O)=O.NCCCC[C@H](N)C(O)=O NWZSZGALRFJKBT-KNIFDHDWSA-N 0.000 description 1
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Classifications

- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D239/00—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings
- C07D239/02—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings
- C07D239/24—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members
- C07D239/28—Heterocyclic compounds containing 1,3-diazine or hydrogenated 1,3-diazine rings not condensed with other rings having three or more double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, directly attached to ring carbon atoms
- C07D239/30—Halogen atoms or nitro radicals
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P17/00—Drugs for dermatological disorders
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P43/00—Drugs for specific purposes, not provided for in groups A61P1/00-A61P41/00
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/08—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 not condensed with other rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/38—Nitrogen atoms
- C07D277/42—Amino or imino radicals substituted by hydrocarbon or substituted hydrocarbon radicals
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D277/00—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings
- C07D277/02—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings
- C07D277/20—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D277/32—Heterocyclic compounds containing 1,3-thiazole or hydrogenated 1,3-thiazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D277/56—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/06—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with only hydrogen atoms, hydrocarbon or substituted hydrocarbon radicals, directly attached to the ring carbon atoms
- C07D333/14—Radicals substituted by singly bound hetero atoms other than halogen
- C07D333/16—Radicals substituted by singly bound hetero atoms other than halogen by oxygen atoms
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D333/00—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom
- C07D333/02—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings
- C07D333/04—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom
- C07D333/26—Heterocyclic compounds containing five-membered rings having one sulfur atom as the only ring hetero atom not condensed with other rings not substituted on the ring sulphur atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D333/28—Halogen atoms

Landscapes

Organic Chemistry (AREA)
Chemical & Material Sciences (AREA)
Health & Medical Sciences (AREA)
General Health & Medical Sciences (AREA)
Veterinary Medicine (AREA)
Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
General Chemical & Material Sciences (AREA)
Pharmacology & Pharmacy (AREA)
Life Sciences & Earth Sciences (AREA)
Animal Behavior & Ethology (AREA)
Chemical Kinetics & Catalysis (AREA)
Public Health (AREA)
Medicinal Chemistry (AREA)
Engineering & Computer Science (AREA)
Bioinformatics & Cheminformatics (AREA)
Dermatology (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Plural Heterocyclic Compounds (AREA)
Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
Agricultural Chemicals And Associated Chemicals (AREA)
Macromolecular Compounds Obtained By Forming Nitrogen-Containing Linkages In General (AREA)

DK003281AA 1980-01-07 1981-01-06 Analogifremgangsmaade til fremstilling af 5-halogenpyrimidin-2-oner eller farmaceutisk acceptable salte deraf DK149892B (da)

Applications Claiming Priority (2)

Application Number	Priority Date	Filing Date	Title
GB8000381		1980-01-07
GB8000381		1980-01-07

Publications (2)

Publication Number	Publication Date
DK3281A DK3281A (da)	1981-07-08
DK149892B true DK149892B (da)	1986-10-20

Family

ID=10510470

Family Applications (1)

Application Number	Title	Priority Date	Filing Date
DK003281AA DK149892B (da)	1980-01-07	1981-01-06	Analogifremgangsmaade til fremstilling af 5-halogenpyrimidin-2-oner eller farmaceutisk acceptable salte deraf

Country Status (13)

Country	Link
US (1)	US4399140A (de)
EP (1)	EP0032131B1 (de)
JP (1)	JPS56150087A (de)
AT (1)	ATE4715T1 (de)
AU (1)	AU543939B2 (de)
CA (1)	CA1168239A (de)
DE (1)	DE3160886D1 (de)
DK (1)	DK149892B (de)
ES (2)	ES498337A0 (de)
IE (1)	IE50765B1 (de)
NO (1)	NO810024L (de)
NZ (1)	NZ195947A (de)
ZA (1)	ZA8164B (de)

Families Citing this family (11)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
CA1159830A (en) *	1980-07-15	1984-01-03	Gordon H. Phillipps	Substituted pyrimidin-2-ones, the salts thereof, processes for their preparation, pharmaceutical compositions containing them and a method therefor
NZ197714A (en) *	1980-07-15	1984-11-09	Glaxo Group Ltd	Substituted pyrimidin-2-ones and pharmaceutical compositions
DE3270525D1 (en) *	1981-01-09	1986-05-22	Nyegaard & Co As	Substituted pyrimidin-2-ones and the salts thereof
EP0087326B1 (de) *	1982-02-24	1987-05-13	Nycomed As	Substituierte Pyrimidin-2-one und deren Salze
SU1235864A1 (ru) *	1983-03-11	1986-06-07	Отделение ордена Ленина института химической физики АН СССР	Нитроксильные производные 5-фторурацила,обладающие противоопухолевой активностью
CN103130732A (zh) *	2011-11-22	2013-06-05	上海博康精细化工有限公司	3,5-二甲基-4-氯甲基异噁唑的制备方法
US20160002204A1 (en) *	2014-07-03	2016-01-07	Board Of Regents, The University Of Texas System	Gls1 inhibitors for treating disease
WO2016004404A2 (en)	2014-07-03	2016-01-07	Board Of Regents, University Of Texas System	Gls1 inhibitors for treating disease
WO2017004359A1 (en)	2015-06-30	2017-01-05	Board Of Regents, University Of Texas System	Gls1 inhibitors for treating disease
SG11201804664XA (en)	2015-12-22	2018-07-30	Univ Texas	Salt forms and polymorphs of (r)-1-(4-(6-(2-(4-(3,3-difluorocyclobutoxy)-6-methylpyridin-2-yl) acetamido) pyridazin-3-yl)-2-fluorobutyl)-n-methyl-1h-1,2,3-triazole-4-carboxamide
RU2020112558A (ru)	2017-10-18	2021-11-18	Боард Оф Регентс, Зе Юниверсити Оф Тексас Систем	Терапия на основе ингибитора глутаминазы

Family Cites Families (5)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US3833586A (en) *	1971-03-25	1974-09-03	Morton Norwich Products Inc	1-(substituted benzyl)-2-(1h)pyrimidones and 1-(substituted benzyl)tetrahydro-2-(1h)pyrimidones
GB1561290A (en) *	1975-10-16	1980-02-20	Nyegaard & Co As	Pyrimid - 2 - ones
US4003900A (en) *	1976-03-11	1977-01-18	Morton-Norwich Products, Inc.	1-Benzyl-5-chloro-2-(1H)-pyrimidone
US4052399A (en) *	1976-09-13	1977-10-04	Morton-Norwich Products, Inc.	1-[2-(Hexahydro-1H-azepino)ethyl]-2(1H)pyrimidone dihydrochloride
US4052400A (en) *	1976-10-29	1977-10-04	Morton-Norwich Products, Inc.	Hypertensive 1-substituted 2(1h)-pyrimidones

1981
- 1981-01-05 ES ES498337A patent/ES498337A0/es active Granted
- 1981-01-06 AT AT81300031T patent/ATE4715T1/de not_active IP Right Cessation
- 1981-01-06 NO NO810024A patent/NO810024L/no unknown
- 1981-01-06 JP JP63181A patent/JPS56150087A/ja active Pending
- 1981-01-06 IE IE13/81A patent/IE50765B1/en unknown
- 1981-01-06 AU AU66016/81A patent/AU543939B2/en not_active Ceased
- 1981-01-06 NZ NZ195947A patent/NZ195947A/xx unknown
- 1981-01-06 ZA ZA00810064A patent/ZA8164B/xx unknown
- 1981-01-06 DE DE8181300031T patent/DE3160886D1/de not_active Expired
- 1981-01-06 CA CA000367958A patent/CA1168239A/en not_active Expired
- 1981-01-06 US US06/222,959 patent/US4399140A/en not_active Expired - Fee Related
- 1981-01-06 DK DK003281AA patent/DK149892B/da unknown
- 1981-01-06 EP EP81300031A patent/EP0032131B1/de not_active Expired
1982
- 1982-02-01 ES ES509219A patent/ES509219A0/es active Granted

Also Published As

Publication number	Publication date
IE810013L (en)	1981-07-07
ZA8164B (en)	1982-03-31
CA1168239A (en)	1984-05-29
NZ195947A (en)	1983-09-02
IE50765B1 (en)	1986-07-09
DE3160886D1 (en)	1983-10-27
AU543939B2 (en)	1985-05-09
EP0032131B1 (de)	1983-09-21
ATE4715T1 (de)	1983-10-15
ES8205399A1 (es)	1982-06-01
AU6601681A (en)	1981-07-16
US4399140A (en)	1983-08-16
NO810024L (no)	1981-07-08
ES8304946A1 (es)	1983-03-16
DK3281A (da)	1981-07-08
ES498337A0 (es)	1982-06-01
EP0032131A1 (de)	1981-07-15
JPS56150087A (en)	1981-11-20
ES509219A0 (es)	1983-03-16

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