NO328103B1 - Fremgangsmate for fremstilling av 2-amino-4-(4-fluorfenyl)-6-alkylpyrimidin-5-karboksylater og mellomprodukter derav - Google Patents

Fremgangsmate for fremstilling av 2-amino-4-(4-fluorfenyl)-6-alkylpyrimidin-5-karboksylater og mellomprodukter derav Download PDF

Info

Publication number: NO328103B1
Authority: NO; Norway
Prior art keywords: methyl; fluorophenyl; reaction; formula; mmol
Prior art date: 1999-07-13

Application number

NO20020163A

Other languages

English (en)

Norwegian (no)

Other versions

NO20020163D0 (no

NO20020163L (no

Inventor

Ulrich Veith

Original Assignee

Lonza Ag Lonza Ltd

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.)

1999-07-13

Filing date

2002-01-11

Publication date

2009-12-07

2002-01-11 Application filed by Lonza Ag Lonza Ltd filed Critical Lonza Ag Lonza Ltd

2002-01-11 Publication of NO20020163D0 publication Critical patent/NO20020163D0/no

2002-01-11 Publication of NO20020163L publication Critical patent/NO20020163L/no

2009-12-07 Publication of NO328103B1 publication Critical patent/NO328103B1/no

Links

238000000034 method Methods 0.000 title claims abstract description 27
238000002360 preparation method Methods 0.000 title claims abstract description 6
239000000543 intermediate Substances 0.000 title description 2
125000001255 4-fluorophenyl group Chemical group [H]C1=C([H])C(*)=C([H])C([H])=C1F 0.000 title 1
239000012467 final product Substances 0.000 claims abstract description 6
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 49
150000001875 compounds Chemical class 0.000 claims description 41
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 36
239000000203 mixture Substances 0.000 claims description 36
238000006243 chemical reaction Methods 0.000 claims description 33
UXBCHKIZBUCCHD-UHFFFAOYSA-N methyl 2-[amino-(4-fluorophenyl)methylidene]-4-methyl-3-oxopentanoate Chemical compound COC(=O)C(C(=O)C(C)C)=C(N)C1=CC=C(F)C=C1 UXBCHKIZBUCCHD-UHFFFAOYSA-N 0.000 claims description 28
125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 17
239000002841 Lewis acid Substances 0.000 claims description 13
150000007517 lewis acids Chemical class 0.000 claims description 13
XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 claims description 12
125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 10
239000001257 hydrogen Substances 0.000 claims description 10
229910052739 hydrogen Inorganic materials 0.000 claims description 10
AEKVBBNGWBBYLL-UHFFFAOYSA-N 4-fluorobenzonitrile Chemical compound FC1=CC=C(C#N)C=C1 AEKVBBNGWBBYLL-UHFFFAOYSA-N 0.000 claims description 9
239000003960 organic solvent Substances 0.000 claims description 8
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 7
125000000217 alkyl group Chemical group 0.000 claims description 5
239000002798 polar solvent Substances 0.000 claims description 3
KPZGRMZPZLOPBS-UHFFFAOYSA-N 1,3-dichloro-2,2-bis(chloromethyl)propane Chemical compound ClCC(CCl)(CCl)CCl KPZGRMZPZLOPBS-UHFFFAOYSA-N 0.000 claims description 2
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 2
239000012442 inert solvent Substances 0.000 claims description 2
239000013067 intermediate product Substances 0.000 claims description 2
KUHQDCIMXXXANM-UHFFFAOYSA-N 2-[amino-(4-fluorophenyl)methylidene]-4-methyl-3-oxopentanoic acid Chemical class CC(C)C(=O)C(C(O)=O)=C(N)C1=CC=C(F)C=C1 KUHQDCIMXXXANM-UHFFFAOYSA-N 0.000 claims 1
238000011065 in-situ storage Methods 0.000 abstract description 9
239000002253 acid Substances 0.000 abstract description 2
150000002148 esters Chemical class 0.000 abstract description 2
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 abstract description 2
IIVUJUOJERNGQX-UHFFFAOYSA-N pyrimidine-5-carboxylic acid Chemical compound OC(=O)C1=CN=CN=C1 IIVUJUOJERNGQX-UHFFFAOYSA-N 0.000 abstract description 2
YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 54
239000007787 solid Substances 0.000 description 40
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 39
239000000243 solution Substances 0.000 description 28
229910000104 sodium hydride Inorganic materials 0.000 description 25
239000012043 crude product Substances 0.000 description 24
CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 22
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 21
239000003921 oil Substances 0.000 description 21
KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 19
239000012074 organic phase Substances 0.000 description 19
239000012312 sodium hydride Substances 0.000 description 19
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 18
239000000725 suspension Substances 0.000 description 17
MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 16
238000001035 drying Methods 0.000 description 16
QPJDMGCKMHUXFD-UHFFFAOYSA-N cyanogen chloride Chemical compound ClC#N QPJDMGCKMHUXFD-UHFFFAOYSA-N 0.000 description 14
238000001914 filtration Methods 0.000 description 13
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
239000008346 aqueous phase Substances 0.000 description 12
238000001704 evaporation Methods 0.000 description 11
229910052943 magnesium sulfate Inorganic materials 0.000 description 11
235000019341 magnesium sulphate Nutrition 0.000 description 11
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 10
-1 for example Chemical class 0.000 description 10
BYVHIGJQQZGFPU-UHFFFAOYSA-N methyl 4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-propan-2-ylpyrimidine-5-carboxylate Chemical compound COC(=O)C1=C(C(C)C)N=C(N(C)S(C)(=O)=O)N=C1C1=CC=C(F)C=C1 BYVHIGJQQZGFPU-UHFFFAOYSA-N 0.000 description 10
239000000047 product Substances 0.000 description 10
229910021627 Tin(IV) chloride Inorganic materials 0.000 description 9
150000004945 aromatic hydrocarbons Chemical class 0.000 description 9
UHNHTTIUNATJKL-UHFFFAOYSA-N n-methylmethanesulfonamide Chemical compound CNS(C)(=O)=O UHNHTTIUNATJKL-UHFFFAOYSA-N 0.000 description 9
MFRIHAYPQRLWNB-UHFFFAOYSA-N sodium tert-butoxide Chemical compound [Na+].CC(C)(C)[O-] MFRIHAYPQRLWNB-UHFFFAOYSA-N 0.000 description 9
HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 9
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
239000002585 base Substances 0.000 description 8
238000002844 melting Methods 0.000 description 8
230000008018 melting Effects 0.000 description 8
239000012071 phase Substances 0.000 description 8
239000011541 reaction mixture Substances 0.000 description 8
230000008020 evaporation Effects 0.000 description 7
239000007789 gas Substances 0.000 description 7
238000004128 high performance liquid chromatography Methods 0.000 description 7
CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 6
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 6
XZMCDFZZKTWFGF-UHFFFAOYSA-N Cyanamide Chemical compound NC#N XZMCDFZZKTWFGF-UHFFFAOYSA-N 0.000 description 6
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 6
238000005481 NMR spectroscopy Methods 0.000 description 6
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 6
238000001816 cooling Methods 0.000 description 6
LZMAQYXBFYTTTM-UHFFFAOYSA-N n-cyano-n-methylmethanesulfonamide Chemical compound N#CN(C)S(C)(=O)=O LZMAQYXBFYTTTM-UHFFFAOYSA-N 0.000 description 6
239000002244 precipitate Substances 0.000 description 6
239000002002 slurry Substances 0.000 description 6
WSLDOOZREJYCGB-UHFFFAOYSA-N 1,2-Dichloroethane Chemical compound ClCCCl WSLDOOZREJYCGB-UHFFFAOYSA-N 0.000 description 5
229910003074 TiCl4 Inorganic materials 0.000 description 5
229910052783 alkali metal Inorganic materials 0.000 description 5
HNNFDXWDCFCVDM-UHFFFAOYSA-N methyl 4-methyl-3-oxopentanoate Chemical compound COC(=O)CC(=O)C(C)C HNNFDXWDCFCVDM-UHFFFAOYSA-N 0.000 description 5
CGRKYEALWSRNJS-UHFFFAOYSA-N sodium;2-methylbutan-2-olate Chemical compound [Na+].CCC(C)(C)[O-] CGRKYEALWSRNJS-UHFFFAOYSA-N 0.000 description 5
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 5
MJBWDEQAUQTVKK-IAGOWNOFSA-N aflatoxin M1 Chemical compound C=1([C@]2(O)C=CO[C@@H]2OC=1C=C(C1=2)OC)C=2OC(=O)C2=C1CCC2=O MJBWDEQAUQTVKK-IAGOWNOFSA-N 0.000 description 4
150000001338 aliphatic hydrocarbons Chemical class 0.000 description 4
239000005457 ice water Substances 0.000 description 4
230000035484 reaction time Effects 0.000 description 4
238000010992 reflux Methods 0.000 description 4
238000003756 stirring Methods 0.000 description 4
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
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 3
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
229910000102 alkali metal hydride Inorganic materials 0.000 description 3
150000008046 alkali metal hydrides Chemical class 0.000 description 3
238000009835 boiling Methods 0.000 description 3
239000012230 colorless oil Substances 0.000 description 3
238000004821 distillation Methods 0.000 description 3
TYISRAUZBAYPKG-UHFFFAOYSA-N ethyl 4-(4-fluorophenyl)-2-[methyl(methylsulfonyl)amino]-6-propan-2-ylpyrimidine-5-carboxylate Chemical compound CCOC(=O)C1=C(C(C)C)N=C(N(C)S(C)(=O)=O)N=C1C1=CC=C(F)C=C1 TYISRAUZBAYPKG-UHFFFAOYSA-N 0.000 description 3
238000000605 extraction Methods 0.000 description 3
238000003818 flash chromatography Methods 0.000 description 3
238000005187 foaming Methods 0.000 description 3
RMYXELUYVYVDAI-UHFFFAOYSA-N methyl 2-amino-4-(4-fluorophenyl)-6-propan-2-ylpyrimidine-5-carboxylate Chemical compound COC(=O)C1=C(C(C)C)N=C(N)N=C1C1=CC=C(F)C=C1 RMYXELUYVYVDAI-UHFFFAOYSA-N 0.000 description 3
229910052757 nitrogen Inorganic materials 0.000 description 3
239000002904 solvent Substances 0.000 description 3
239000007858 starting material Substances 0.000 description 3
RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 description 2
ALIOTQKCOLLPGP-UHFFFAOYSA-N 2-amino-4-(4-fluorophenyl)-6-propan-2-ylpyrimidine-5-carboxylic acid Chemical compound CC(C)C1=NC(N)=NC(C=2C=CC(F)=CC=2)=C1C(O)=O ALIOTQKCOLLPGP-UHFFFAOYSA-N 0.000 description 2
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 2
KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 2
WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 2
BAVYZALUXZFZLV-UHFFFAOYSA-N Methylamine Chemical compound NC BAVYZALUXZFZLV-UHFFFAOYSA-N 0.000 description 2
FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 2
CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 description 2
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 2
229910000288 alkali metal carbonate Inorganic materials 0.000 description 2
150000008041 alkali metal carbonates Chemical class 0.000 description 2
150000001340 alkali metals Chemical class 0.000 description 2
VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 description 2
ATDGTVJJHBUTRL-UHFFFAOYSA-N cyanogen bromide Chemical compound BrC#N ATDGTVJJHBUTRL-UHFFFAOYSA-N 0.000 description 2
239000003480 eluent Substances 0.000 description 2
239000012065 filter cake Substances 0.000 description 2
239000000706 filtrate Substances 0.000 description 2
JMANVNJQNLATNU-UHFFFAOYSA-N glycolonitrile Natural products N#CC#N JMANVNJQNLATNU-UHFFFAOYSA-N 0.000 description 2
238000002955 isolation Methods 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
238000000425 proton nuclear magnetic resonance spectrum Methods 0.000 description 2
239000000741 silica gel Substances 0.000 description 2
229910002027 silica gel Inorganic materials 0.000 description 2
229910052708 sodium Inorganic materials 0.000 description 2
239000011734 sodium Substances 0.000 description 2
CDBYLPFSWZWCQE-UHFFFAOYSA-L sodium carbonate Substances [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
239000000126 substance Substances 0.000 description 2
238000005406 washing Methods 0.000 description 2
239000008096 xylene Substances 0.000 description 2
SCYULBFZEHDVBN-UHFFFAOYSA-N 1,1-Dichloroethane Chemical compound CC(Cl)Cl SCYULBFZEHDVBN-UHFFFAOYSA-N 0.000 description 1
IWEPSGGZINUNSM-UHFFFAOYSA-N 2-sulfonyl-1h-pyrimidine Chemical compound O=S(=O)=C1N=CC=CN1 IWEPSGGZINUNSM-UHFFFAOYSA-N 0.000 description 1
NHQDETIJWKXCTC-UHFFFAOYSA-N 3-chloroperbenzoic acid Chemical compound OOC(=O)C1=CC=CC(Cl)=C1 NHQDETIJWKXCTC-UHFFFAOYSA-N 0.000 description 1
UOQXIWFBQSVDPP-UHFFFAOYSA-N 4-fluorobenzaldehyde Chemical compound FC1=CC=C(C=O)C=C1 UOQXIWFBQSVDPP-UHFFFAOYSA-N 0.000 description 1
239000012359 Methanesulfonyl chloride Substances 0.000 description 1
ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 1
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
FYJKEHKQUPSJDH-UHFFFAOYSA-N [dimethyl-(trimethylsilylamino)silyl]methane;potassium Chemical compound [K].C[Si](C)(C)N[Si](C)(C)C FYJKEHKQUPSJDH-UHFFFAOYSA-N 0.000 description 1
150000001298 alcohols Chemical class 0.000 description 1
150000001339 alkali metal compounds Chemical class 0.000 description 1
229910052782 aluminium Inorganic materials 0.000 description 1
XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 1
125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
235000012255 calcium oxide Nutrition 0.000 description 1
125000004432 carbon atom Chemical group C* 0.000 description 1
CPPKAGUPTKIMNP-UHFFFAOYSA-N cyanogen fluoride Chemical compound FC#N CPPKAGUPTKIMNP-UHFFFAOYSA-N 0.000 description 1
WPBXOELOQKLBDF-UHFFFAOYSA-N cyanogen iodide Chemical compound IC#N WPBXOELOQKLBDF-UHFFFAOYSA-N 0.000 description 1
238000010790 dilution Methods 0.000 description 1
239000012895 dilution Substances 0.000 description 1
150000002170 ethers Chemical class 0.000 description 1
XCLDSQRVMMXWMS-UHFFFAOYSA-N ethyl 4-methyl-3-oxopentanoate Chemical compound CCOC(=O)CC(=O)C(C)C XCLDSQRVMMXWMS-UHFFFAOYSA-N 0.000 description 1
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
239000004744 fabric Substances 0.000 description 1
125000004051 hexyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
150000002431 hydrogen Chemical class 0.000 description 1
230000007062 hydrolysis Effects 0.000 description 1
238000006460 hydrolysis reaction Methods 0.000 description 1
239000003112 inhibitor Substances 0.000 description 1
125000000959 isobutyl group Chemical group [H]C([H])([H])C([H])(C([H])([H])[H])C([H])([H])* 0.000 description 1
229910052808 lithium carbonate Inorganic materials 0.000 description 1
229910000103 lithium hydride Inorganic materials 0.000 description 1
238000004519 manufacturing process Methods 0.000 description 1
QARBMVPHQWIHKH-UHFFFAOYSA-N methanesulfonyl chloride Chemical compound CS(Cl)(=O)=O QARBMVPHQWIHKH-UHFFFAOYSA-N 0.000 description 1
NNBBQNFHCVVQHZ-UHFFFAOYSA-N methyl carbamimidothioate;sulfuric acid Chemical compound CSC(N)=N.OS(O)(=O)=O NNBBQNFHCVVQHZ-UHFFFAOYSA-N 0.000 description 1
125000000250 methylamino group Chemical group [H]N(*)C([H])([H])[H] 0.000 description 1
HSYNUFPBJIYFLD-UHFFFAOYSA-N n-cyanomethanesulfonamide Chemical compound CS(=O)(=O)NC#N HSYNUFPBJIYFLD-UHFFFAOYSA-N 0.000 description 1
238000000655 nuclear magnetic resonance spectrum Methods 0.000 description 1
125000001147 pentyl group Chemical group C(CCCC)* 0.000 description 1
239000003495 polar organic solvent Substances 0.000 description 1
239000011591 potassium Substances 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
229910000105 potassium hydride Inorganic materials 0.000 description 1
LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 1
ZRLVQFQTCMUIRM-UHFFFAOYSA-N potassium;2-methylbutan-2-olate Chemical compound [K+].CCC(C)(C)[O-] ZRLVQFQTCMUIRM-UHFFFAOYSA-N 0.000 description 1
238000003672 processing method Methods 0.000 description 1
125000001436 propyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])[H] 0.000 description 1
125000002914 sec-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
WRIKHQLVHPKCJU-UHFFFAOYSA-N sodium bis(trimethylsilyl)amide Chemical compound C[Si](C)(C)N([Na])[Si](C)(C)C WRIKHQLVHPKCJU-UHFFFAOYSA-N 0.000 description 1
229910000029 sodium carbonate Inorganic materials 0.000 description 1
229910052938 sodium sulfate Inorganic materials 0.000 description 1
235000011152 sodium sulphate Nutrition 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
UBZYKBZMAMTNKW-UHFFFAOYSA-J titanium tetrabromide Chemical compound Br[Ti](Br)(Br)Br UBZYKBZMAMTNKW-UHFFFAOYSA-J 0.000 description 1

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
- C07D239/32—One oxygen, sulfur or nitrogen atom
- C07D239/42—One nitrogen atom
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C229/00—Compounds containing amino and carboxyl groups bound to the same carbon skeleton
- C07C229/02—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton
- C07C229/34—Compounds containing amino and carboxyl groups bound to the same carbon skeleton having amino and carboxyl groups bound to acyclic carbon atoms of the same carbon skeleton the carbon skeleton containing six-membered aromatic rings
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C311/00—Amides of sulfonic acids, i.e. compounds having singly-bound oxygen atoms of sulfo groups replaced by nitrogen atoms, not being part of nitro or nitroso groups
- C07C311/01—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms
- C07C311/02—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton
- C07C311/03—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms
- C07C311/05—Sulfonamides having sulfur atoms of sulfonamide groups bound to acyclic carbon atoms of an acyclic saturated carbon skeleton having the nitrogen atoms of the sulfonamide groups bound to hydrogen atoms or to acyclic carbon atoms to acyclic carbon atoms of hydrocarbon radicals substituted by nitrogen atoms, not being part of nitro or nitroso groups
- 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

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Chemical & Material Sciences (AREA)
Organic Chemistry (AREA)
Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)

NO20020163A 1999-07-13 2002-01-11 Fremgangsmate for fremstilling av 2-amino-4-(4-fluorfenyl)-6-alkylpyrimidin-5-karboksylater og mellomprodukter derav NO328103B1 (no)

Applications Claiming Priority (6)

Application Number	Priority Date	Filing Date	Title
EP99113711		1999-07-13
EP99120417		1999-10-14
US18537100P	2000-02-28	2000-02-28
US18546500P	2000-02-28	2000-02-28
EP00106303		2000-03-23
PCT/EP2000/006099 WO2001004100A1 (en)	1999-07-13	2000-06-30	Process for preparing 2-amino-4-(4-fluorphenyl)-6-alkylpyrimidine-5-carboxylate

Publications (3)

Publication Number	Publication Date
NO20020163D0 NO20020163D0 (no)	2002-01-11
NO20020163L NO20020163L (no)	2002-01-11
NO328103B1 true NO328103B1 (no)	2009-12-07

Family

ID=27513029

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
NO20020163A NO328103B1 (no)	1999-07-13	2002-01-11	Fremgangsmate for fremstilling av 2-amino-4-(4-fluorfenyl)-6-alkylpyrimidin-5-karboksylater og mellomprodukter derav
NO20092393A NO334937B1 (no)	1999-07-13	2009-06-23	Fremgangsmåte for fremstilling av N-cyano-N-alkylalkansulfonamider og 4-fenylpyrimidiner samt slike forbindelser

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
NO20092393A NO334937B1 (no)	1999-07-13	2009-06-23	Fremgangsmåte for fremstilling av N-cyano-N-alkylalkansulfonamider og 4-fenylpyrimidiner samt slike forbindelser

Country Status (17)

Country	Link
US (3)	US6579984B1 (cs)
EP (1)	EP1194414B1 (cs)
JP (1)	JP4649813B2 (cs)
KR (1)	KR100649927B1 (cs)
CN (1)	CN1164577C (cs)
AT (1)	ATE307120T1 (cs)
AU (1)	AU6266600A (cs)
CA (1)	CA2378782C (cs)
CZ (1)	CZ304307B6 (cs)
DE (1)	DE60023296T2 (cs)
ES (1)	ES2251392T3 (cs)
HK (1)	HK1046682B (cs)
HU (1)	HU228303B1 (cs)
NO (2)	NO328103B1 (cs)
PL (1)	PL211797B1 (cs)
SK (1)	SK285993B6 (cs)
WO (1)	WO2001004100A1 (cs)

Families Citing this family (12)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
GB0003305D0 (en)	2000-02-15	2000-04-05	Zeneca Ltd	Pyrimidine derivatives
AR034772A1 (es) *	2001-07-13	2004-03-17	Astrazeneca Uk Ltd	Preparacion de los compuestos de aminopirimidina
RU2301801C2 (ru) *	2001-07-13	2007-06-27	АстраЗенека Ю-Кей Лимитед	Способ получения сульфониламинопиримидиновых соединений (варианты), промежуточные продукты и способы их получения
GB0218781D0 (en) *	2002-08-13	2002-09-18	Astrazeneca Ab	Chemical process
ATE448209T1 (de)	2002-12-16	2009-11-15	Astrazeneca Uk Ltd	Verfahren zur herstellung von pyrimidinverbindungen
GB0428328D0 (en) *	2004-12-24	2005-02-02	Astrazeneca Uk Ltd	Chemical process
EP2423195A1 (en)	2010-07-26	2012-02-29	LEK Pharmaceuticals d.d.	Process for the preparation of key intermediates for the synthesis of statins or pharmaceutically acceptable salts thereof
ES2879314T3 (es)	2010-08-18	2021-11-22	Biosplice Therapeutics Inc	Dicetonas e hidroxicetonas como activadores de la vía de señalización de catenina
PL2968249T3 (pl)	2013-02-22	2019-06-28	Samumed, Llc	Gamma-diketony jako aktywatory szlaku sygnałowego Wnt/beta-kateniny
CN103910644B (zh) *	2014-04-21	2015-06-24	广西师范大学	β-烯胺酮酯类化合物及其合成方法和应用
US9795550B2 (en)	2014-08-20	2017-10-24	Samumed, Llc	Gamma-diketones for treatment and prevention of aging skin and wrinkles
CN110483341A (zh) *	2019-07-23	2019-11-22	上海药明康德新药开发有限公司	一种1-氰基-n-甲基甲磺酰胺的合成方法

Family Cites Families (4)

* Cited by examiner, † Cited by third party
Publication number	Priority date	Publication date	Assignee	Title
US4013706A (en) *	1973-11-14	1977-03-22	Sucreries Du Soissonnais Et Compagnie Sucriere	Derivatives of substituted urea, acyl ureas, and sulphonyl ureas, and a process for producing the same
DE3717815A1 (de) *	1987-05-27	1988-12-15	Bayer Ag	Fungizide mittel auf basis von substituierten cyanamiden
JP2648897B2 (ja)	1991-07-01	1997-09-03	塩野義製薬株式会社	ピリミジン誘導体
JP3197971B2 (ja) *	1993-03-01	2001-08-13	塩野義製薬株式会社	５−カルボアルコキシピリミジン誘導体の合成方法

2000
- 2000-06-30 PL PL353058A patent/PL211797B1/pl unknown
- 2000-06-30 HK HK02108215.0A patent/HK1046682B/zh not_active IP Right Cessation
- 2000-06-30 WO PCT/EP2000/006099 patent/WO2001004100A1/en not_active Ceased
- 2000-06-30 CA CA002378782A patent/CA2378782C/en not_active Expired - Lifetime
- 2000-06-30 KR KR1020027000488A patent/KR100649927B1/ko not_active Expired - Fee Related
- 2000-06-30 AT AT00949231T patent/ATE307120T1/de active
- 2000-06-30 US US10/030,077 patent/US6579984B1/en not_active Expired - Lifetime
- 2000-06-30 CN CNB008116768A patent/CN1164577C/zh not_active Expired - Lifetime
- 2000-06-30 DE DE60023296T patent/DE60023296T2/de not_active Expired - Lifetime
- 2000-06-30 JP JP2001509711A patent/JP4649813B2/ja not_active Expired - Lifetime
- 2000-06-30 ES ES00949231T patent/ES2251392T3/es not_active Expired - Lifetime
- 2000-06-30 SK SK22-2002A patent/SK285993B6/sk not_active IP Right Cessation
- 2000-06-30 AU AU62666/00A patent/AU6266600A/en not_active Abandoned
- 2000-06-30 CZ CZ2002-61A patent/CZ304307B6/cs not_active IP Right Cessation
- 2000-06-30 EP EP00949231A patent/EP1194414B1/en not_active Expired - Lifetime
- 2000-06-30 HU HU0202006A patent/HU228303B1/hu not_active IP Right Cessation
2002
- 2002-01-11 NO NO20020163A patent/NO328103B1/no not_active IP Right Cessation
2003
- 2003-05-23 US US10/443,797 patent/US6710178B2/en not_active Expired - Lifetime
2004
- 2004-03-23 US US10/806,315 patent/US6984757B2/en not_active Expired - Lifetime
2009
- 2009-06-23 NO NO20092393A patent/NO334937B1/no not_active IP Right Cessation

Also Published As

Publication number	Publication date
CA2378782C (en)	2009-11-10
NO20092393L (no)	2002-01-11
EP1194414A1 (en)	2002-04-10
HUP0202006A2 (hu)	2002-12-28
DE60023296D1 (de)	2006-03-02
HK1046682B (zh)	2005-04-08
ATE307120T1 (de)	2005-11-15
NO334937B1 (no)	2014-07-21
CZ304307B6 (cs)	2014-02-26
CN1164577C (zh)	2004-09-01
KR100649927B1 (ko)	2006-11-27
SK222002A3 (en)	2002-06-04
WO2001004100A1 (en)	2001-01-18
ES2251392T3 (es)	2006-05-01
US6984757B2 (en)	2006-01-10
JP2003504359A (ja)	2003-02-04
AU6266600A (en)	2001-01-30
US6710178B2 (en)	2004-03-23
CA2378782A1 (en)	2001-01-18
NO20020163D0 (no)	2002-01-11
US20040181065A1 (en)	2004-09-16
PL353058A1 (en)	2003-10-06
CZ200261A3 (cs)	2002-05-15
CN1370151A (zh)	2002-09-18
NO20020163L (no)	2002-01-11
JP4649813B2 (ja)	2011-03-16
SK285993B6 (sk)	2008-01-07
HK1046682A1 (en)	2003-01-24
HUP0202006A3 (en)	2003-02-28
DE60023296T2 (de)	2006-07-20
PL211797B1 (pl)	2012-06-29
EP1194414B1 (en)	2005-10-19
KR20020012007A (ko)	2002-02-09
US20030199695A1 (en)	2003-10-23
HU228303B1 (hu)	2013-03-28
US6579984B1 (en)	2003-06-17

Legal Events

Date	Code	Title	Description
2020-01-27	MM1K	Lapsed by not paying the annual fees

Publication	Publication Date	Title
NO334937B1 (no)	2014-07-21	Fremgangsmåte for fremstilling av N-cyano-N-alkylalkansulfonamider og 4-fenylpyrimidiner samt slike forbindelser
JP2023027091A (ja)	2023-03-01	アミノピリミジン誘導体を調製するための改善されたプロセス
CA2646795A1 (en)	2009-06-18	Process for the preparation of bosentan
KR20170029656A (ko)	2017-03-15	피리미딘 술파미드 유도체의 제조 방법
EP2350025A1 (en)	2011-08-03	An improved process for preparing pyrimidine propenaldehyde
EP0483204B1 (en)	1995-05-24	Process for preparing 2,5-diamino-4,6-dichloropyrimidine
KR100535450B1 (ko)	2006-03-30	피리미딘유도체의제조방법
WO2008059519A2 (en)	2008-05-22	A process for the preparation of intermediates of rosuvastatin
US6187926B1 (en)	2001-02-13	Process for producing quinolone derivatives
US5266697A (en)	1993-11-30	Process for the production of 2-substituted 4,6-dialkoxypyrimidines
AU658965B2 (en)	1995-05-04	N-5-protected 2,5-diamino-4,6-dichloro-pyrimidines and processes for their preparation
JP6375374B2 (ja)	2018-08-15	ピリミジン中間体の製造方法
WO2011021216A2 (en)	2011-02-24	Improved process for the preparation of 4-(1,1-dimethylethyl)-n-[6-(2-hydroxyethoxy)-5-(2-methoxyphenoxy)[2,2'-bipyrimidin]-4-yl]benzenesulfonamide
JPH11147879A (ja)	1999-06-02	非対称４，６−ビス（アリールオキシ）ピリミジン化合物の改良された製造方法
WO2017093903A1 (en)	2017-06-08	An improved process for the preparation of macitentan
EP0515464B1 (en)	1994-10-19	Process for preparing uracil derivatives
WO2011121598A1 (en)	2011-10-06	Crystalline 7-[4-(4-fluorophenyl)-6-isopropyl-2-(methanesulfonyl-methyl-amino)-pyrimidin-5-yl]-3(r)-hydroxy-5-oxo-hept-6-enoic acid methyl ester and process thereof