RU2458056C2 - Способ получения 4-(1,6-дигидро-6-оксо-2-пиримидинил)амино-бензонитрила - Google Patents
Способ получения 4-(1,6-дигидро-6-оксо-2-пиримидинил)амино-бензонитрила Download PDFInfo
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- RU2458056C2 RU2458056C2 RU2007148968/04A RU2007148968A RU2458056C2 RU 2458056 C2 RU2458056 C2 RU 2458056C2 RU 2007148968/04 A RU2007148968/04 A RU 2007148968/04A RU 2007148968 A RU2007148968 A RU 2007148968A RU 2458056 C2 RU2458056 C2 RU 2458056C2
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- RU
- Russia
- Prior art keywords
- compound
- formula
- amino
- alkyl
- ammonium
- Prior art date
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- 238000000034 method Methods 0.000 title claims abstract description 33
- BBNOJNASJQRRSH-UHFFFAOYSA-N 4-[(6-oxo-1h-pyrimidin-2-yl)amino]benzonitrile Chemical compound N1C(=O)C=CN=C1NC1=CC=C(C#N)C=C1 BBNOJNASJQRRSH-UHFFFAOYSA-N 0.000 title abstract description 5
- 150000001875 compounds Chemical class 0.000 claims abstract description 71
- 238000006243 chemical reaction Methods 0.000 claims abstract description 24
- 150000003839 salts Chemical class 0.000 claims abstract description 18
- -1 malonic acid ester Chemical class 0.000 claims abstract description 15
- YIBOMRUWOWDFLG-ONEGZZNKSA-N rilpivirine Chemical compound CC1=CC(\C=C\C#N)=CC(C)=C1NC1=CC=NC(NC=2C=CC(=CC=2)C#N)=N1 YIBOMRUWOWDFLG-ONEGZZNKSA-N 0.000 claims abstract description 15
- 238000005933 dealkoxycarbonylation reaction Methods 0.000 claims abstract description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-O Ammonium Chemical compound [NH4+] QGZKDVFQNNGYKY-UHFFFAOYSA-O 0.000 claims abstract description 9
- OFOBLEOULBTSOW-UHFFFAOYSA-N Propanedioic acid Natural products OC(=O)CC(O)=O OFOBLEOULBTSOW-UHFFFAOYSA-N 0.000 claims abstract description 5
- 150000001450 anions Chemical group 0.000 claims abstract description 4
- 239000012442 inert solvent Substances 0.000 claims abstract description 4
- 229910052751 metal Inorganic materials 0.000 claims abstract description 3
- 239000002184 metal Substances 0.000 claims abstract description 3
- 230000000269 nucleophilic effect Effects 0.000 claims abstract description 3
- 239000002904 solvent Substances 0.000 claims description 17
- 239000002253 acid Substances 0.000 claims description 15
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical group CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 claims description 12
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 claims description 12
- 239000011541 reaction mixture Substances 0.000 claims description 12
- 125000000217 alkyl group Chemical group 0.000 claims description 11
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 claims description 8
- 239000001632 sodium acetate Substances 0.000 claims description 8
- 235000017281 sodium acetate Nutrition 0.000 claims description 8
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 7
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 6
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 claims description 6
- 238000004519 manufacturing process Methods 0.000 claims description 6
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 6
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 5
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 4
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 4
- 229910052783 alkali metal Inorganic materials 0.000 claims description 4
- 238000009833 condensation Methods 0.000 claims description 4
- 230000005494 condensation Effects 0.000 claims description 4
- GNOIPBMMFNIUFM-UHFFFAOYSA-N hexamethylphosphoric triamide Chemical compound CN(C)P(=O)(N(C)C)N(C)C GNOIPBMMFNIUFM-UHFFFAOYSA-N 0.000 claims description 4
- 125000005599 alkyl carboxylate group Chemical group 0.000 claims description 3
- 239000000010 aprotic solvent Substances 0.000 claims description 3
- 230000003993 interaction Effects 0.000 claims description 3
- 238000002955 isolation Methods 0.000 claims description 3
- JNRBSZUSHVFWIK-ONEGZZNKSA-N (e)-3-(4-amino-3,5-dimethylphenyl)prop-2-enenitrile Chemical compound CC1=CC(\C=C\C#N)=CC(C)=C1N JNRBSZUSHVFWIK-ONEGZZNKSA-N 0.000 claims description 2
- IHXNIOYEXQWUNI-UHFFFAOYSA-N 4,5-dihydro-1h-pyrimidin-6-one Chemical compound O=C1CCN=CN1 IHXNIOYEXQWUNI-UHFFFAOYSA-N 0.000 claims description 2
- BJJSUOOEBCCLNY-UHFFFAOYSA-N 4-iodo-2,6-dimethylaniline Chemical compound CC1=CC(I)=CC(C)=C1N BJJSUOOEBCCLNY-UHFFFAOYSA-N 0.000 claims description 2
- NLHHRLWOUZZQLW-UHFFFAOYSA-N Acrylonitrile Chemical compound C=CC#N NLHHRLWOUZZQLW-UHFFFAOYSA-N 0.000 claims description 2
- XFXPMWWXUTWYJX-UHFFFAOYSA-N Cyanide Chemical group N#[C-] XFXPMWWXUTWYJX-UHFFFAOYSA-N 0.000 claims description 2
- 239000002585 base Substances 0.000 claims description 2
- 238000005658 halogenation reaction Methods 0.000 claims description 2
- XGXNTJHZPBRBHJ-UHFFFAOYSA-N n-phenylpyrimidin-2-amine Chemical compound N=1C=CC=NC=1NC1=CC=CC=C1 XGXNTJHZPBRBHJ-UHFFFAOYSA-N 0.000 claims description 2
- 229910052763 palladium Inorganic materials 0.000 claims description 2
- RLOWWWKZYUNIDI-UHFFFAOYSA-N phosphinic chloride Chemical compound ClP=O RLOWWWKZYUNIDI-UHFFFAOYSA-N 0.000 claims description 2
- ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims 2
- 150000001340 alkali metals Chemical class 0.000 claims 2
- CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims 1
- SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims 1
- 150000004820 halides Chemical group 0.000 claims 1
- 150000002148 esters Chemical class 0.000 abstract description 5
- 239000007795 chemical reaction product Substances 0.000 abstract description 4
- 239000003814 drug Substances 0.000 abstract description 4
- 150000002357 guanidines Chemical class 0.000 abstract description 4
- 239000000126 substance Substances 0.000 abstract description 4
- 208000031886 HIV Infections Diseases 0.000 abstract description 2
- 208000037357 HIV infectious disease Diseases 0.000 abstract description 2
- QWIKJMKYJNKLDW-UHFFFAOYSA-N OC(=O)N1CCC(=O)N=C1 Chemical compound OC(=O)N1CCC(=O)N=C1 QWIKJMKYJNKLDW-UHFFFAOYSA-N 0.000 abstract description 2
- 150000003863 ammonium salts Chemical class 0.000 abstract description 2
- 230000000694 effects Effects 0.000 abstract description 2
- 208000033519 human immunodeficiency virus infectious disease Diseases 0.000 abstract description 2
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 abstract 1
- 230000000840 anti-viral effect Effects 0.000 abstract 1
- 239000000203 mixture Substances 0.000 description 17
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- 239000000543 intermediate Substances 0.000 description 14
- 230000015572 biosynthetic process Effects 0.000 description 10
- 238000003786 synthesis reaction Methods 0.000 description 10
- 239000002244 precipitate Substances 0.000 description 8
- ILAYIAGXTHKHNT-UHFFFAOYSA-N 4-[4-(2,4,6-trimethyl-phenylamino)-pyrimidin-2-ylamino]-benzonitrile Chemical compound CC1=CC(C)=CC(C)=C1NC1=CC=NC(NC=2C=CC(=CC=2)C#N)=N1 ILAYIAGXTHKHNT-UHFFFAOYSA-N 0.000 description 6
- SCVFZCLFOSHCOH-UHFFFAOYSA-M potassium acetate Chemical compound [K+].CC([O-])=O SCVFZCLFOSHCOH-UHFFFAOYSA-M 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- 241000725303 Human immunodeficiency virus Species 0.000 description 5
- 241000700605 Viruses Species 0.000 description 5
- 150000007513 acids Chemical class 0.000 description 5
- QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 3
- LSDPWZHWYPCBBB-UHFFFAOYSA-N Methanethiol Chemical compound SC LSDPWZHWYPCBBB-UHFFFAOYSA-N 0.000 description 3
- 159000000021 acetate salts Chemical class 0.000 description 3
- 229910052799 carbon Inorganic materials 0.000 description 3
- 229940079593 drug Drugs 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 235000011056 potassium acetate Nutrition 0.000 description 3
- 238000002360 preparation method Methods 0.000 description 3
- 239000000047 product Substances 0.000 description 3
- BTDGLZSKNFJBER-UHFFFAOYSA-N 2-(4-cyanophenyl)guanidine Chemical compound NC(=N)NC1=CC=C(C#N)C=C1 BTDGLZSKNFJBER-UHFFFAOYSA-N 0.000 description 2
- 208000030507 AIDS Diseases 0.000 description 2
- CPELXLSAUQHCOX-UHFFFAOYSA-M Bromide Chemical compound [Br-] CPELXLSAUQHCOX-UHFFFAOYSA-M 0.000 description 2
- VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 2
- 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 2
- 229940122313 Nucleoside reverse transcriptase inhibitor Drugs 0.000 description 2
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 description 2
- WCUXLLCKKVVCTQ-UHFFFAOYSA-M Potassium chloride Chemical compound [Cl-].[K+] WCUXLLCKKVVCTQ-UHFFFAOYSA-M 0.000 description 2
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 2
- 239000003513 alkali Substances 0.000 description 2
- 239000003153 chemical reaction reagent Substances 0.000 description 2
- 238000001816 cooling Methods 0.000 description 2
- RHFZTBSULNJWEI-UHFFFAOYSA-N dimethyl 2-(methoxymethylidene)propanedioate Chemical compound COC=C(C(=O)OC)C(=O)OC RHFZTBSULNJWEI-UHFFFAOYSA-N 0.000 description 2
- XBDQKXXYIPTUBI-UHFFFAOYSA-N dimethylselenoniopropionate Natural products CCC(O)=O XBDQKXXYIPTUBI-UHFFFAOYSA-N 0.000 description 2
- 239000003112 inhibitor Substances 0.000 description 2
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 2
- 239000002726 nonnucleoside reverse transcriptase inhibitor Substances 0.000 description 2
- 150000007524 organic acids Chemical class 0.000 description 2
- IOLCXVTUBQKXJR-UHFFFAOYSA-M potassium bromide Chemical compound [K+].[Br-] IOLCXVTUBQKXJR-UHFFFAOYSA-M 0.000 description 2
- 230000035484 reaction time Effects 0.000 description 2
- 239000003419 rna directed dna polymerase inhibitor Substances 0.000 description 2
- 229910052708 sodium Inorganic materials 0.000 description 2
- JHJLBTNAGRQEKS-UHFFFAOYSA-M sodium bromide Chemical compound [Na+].[Br-] JHJLBTNAGRQEKS-UHFFFAOYSA-M 0.000 description 2
- 125000001424 substituent group Chemical group 0.000 description 2
- 238000002560 therapeutic procedure Methods 0.000 description 2
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 2
- KWVPRPSXBZNOHS-UHFFFAOYSA-N 2,4,6-Trimethylaniline Chemical compound CC1=CC(C)=C(N)C(C)=C1 KWVPRPSXBZNOHS-UHFFFAOYSA-N 0.000 description 1
- FQWBGZVXVRORRM-UHFFFAOYSA-N 2-pyrimidin-2-yloxypyrimidine Chemical class N=1C=CC=NC=1OC1=NC=CC=N1 FQWBGZVXVRORRM-UHFFFAOYSA-N 0.000 description 1
- YIBOMRUWOWDFLG-UHFFFAOYSA-N 4-[[4-[4-(2-cyanoethenyl)-2,6-dimethylanilino]pyrimidin-2-yl]amino]benzonitrile Chemical compound CC1=CC(C=CC#N)=CC(C)=C1NC1=CC=NC(NC=2C=CC(=CC=2)C#N)=N1 YIBOMRUWOWDFLG-UHFFFAOYSA-N 0.000 description 1
- YIBOMRUWOWDFLG-ARJAWSKDSA-N 4-[[4-[4-[(z)-2-cyanoethenyl]-2,6-dimethylanilino]pyrimidin-2-yl]amino]benzonitrile Chemical compound CC1=CC(\C=C/C#N)=CC(C)=C1NC1=CC=NC(NC=2C=CC(=CC=2)C#N)=N1 YIBOMRUWOWDFLG-ARJAWSKDSA-N 0.000 description 1
- COVZYZSDYWQREU-UHFFFAOYSA-N Busulfan Chemical compound CS(=O)(=O)OCCCCOS(C)(=O)=O COVZYZSDYWQREU-UHFFFAOYSA-N 0.000 description 1
- BHPQYMZQTOCNFJ-UHFFFAOYSA-N Calcium cation Chemical compound [Ca+2] BHPQYMZQTOCNFJ-UHFFFAOYSA-N 0.000 description 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical class CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 1
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 description 1
- 229930194542 Keto Natural products 0.000 description 1
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 description 1
- FYYHWMGAXLPEAU-UHFFFAOYSA-N Magnesium Chemical compound [Mg] FYYHWMGAXLPEAU-UHFFFAOYSA-N 0.000 description 1
- GRYLNZFGIOXLOG-UHFFFAOYSA-N Nitric acid Chemical compound O[N+]([O-])=O GRYLNZFGIOXLOG-UHFFFAOYSA-N 0.000 description 1
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 description 1
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 1
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
- 238000010521 absorption reaction Methods 0.000 description 1
- 239000004480 active ingredient Substances 0.000 description 1
- 229910001413 alkali metal ion Inorganic materials 0.000 description 1
- 229910001420 alkaline earth metal ion Inorganic materials 0.000 description 1
- 229910000147 aluminium phosphate Inorganic materials 0.000 description 1
- 230000000844 anti-bacterial effect Effects 0.000 description 1
- 230000036436 anti-hiv Effects 0.000 description 1
- 238000013459 approach Methods 0.000 description 1
- 239000003899 bactericide agent Substances 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- QSRFYFHZPSGRQX-UHFFFAOYSA-N benzyl(tributyl)azanium Chemical compound CCCC[N+](CCCC)(CCCC)CC1=CC=CC=C1 QSRFYFHZPSGRQX-UHFFFAOYSA-N 0.000 description 1
- YOUGRGFIHBUKRS-UHFFFAOYSA-N benzyl(trimethyl)azanium Chemical compound C[N+](C)(C)CC1=CC=CC=C1 YOUGRGFIHBUKRS-UHFFFAOYSA-N 0.000 description 1
- 230000005540 biological transmission Effects 0.000 description 1
- 238000009835 boiling Methods 0.000 description 1
- 229910001424 calcium ion Inorganic materials 0.000 description 1
- 150000001721 carbon Chemical group 0.000 description 1
- 125000004432 carbon atom Chemical group C* 0.000 description 1
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
- 150000001733 carboxylic acid esters Chemical group 0.000 description 1
- KXZJHVJKXJLBKO-UHFFFAOYSA-N chembl1408157 Chemical compound N=1C2=CC=CC=C2C(C(=O)O)=CC=1C1=CC=C(O)C=C1 KXZJHVJKXJLBKO-UHFFFAOYSA-N 0.000 description 1
- 239000003795 chemical substances by application Substances 0.000 description 1
- 238000004140 cleaning Methods 0.000 description 1
- 238000002648 combination therapy Methods 0.000 description 1
- 238000006482 condensation reaction Methods 0.000 description 1
- HCAJEUSONLESMK-UHFFFAOYSA-N cyclohexylsulfamic acid Chemical compound OS(=O)(=O)NC1CCCCC1 HCAJEUSONLESMK-UHFFFAOYSA-N 0.000 description 1
- 230000006324 decarbonylation Effects 0.000 description 1
- 238000006606 decarbonylation reaction Methods 0.000 description 1
- LTMHNWPUDSTBKD-UHFFFAOYSA-N diethyl 2-(ethoxymethylidene)propanedioate Chemical compound CCOC=C(C(=O)OCC)C(=O)OCC LTMHNWPUDSTBKD-UHFFFAOYSA-N 0.000 description 1
- 239000012458 free base Substances 0.000 description 1
- 229910052736 halogen Inorganic materials 0.000 description 1
- 150000002367 halogens Chemical class 0.000 description 1
- 230000005802 health problem Effects 0.000 description 1
- 150000004677 hydrates Chemical class 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 238000002329 infrared spectrum Methods 0.000 description 1
- 230000002401 inhibitory effect Effects 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
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- 125000000468 ketone group Chemical group 0.000 description 1
- 229910052744 lithium Inorganic materials 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 description 1
- 150000007522 mineralic acids Chemical class 0.000 description 1
- 230000035772 mutation Effects 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- 229910017604 nitric acid Inorganic materials 0.000 description 1
- 150000002825 nitriles Chemical class 0.000 description 1
- 229940042402 non-nucleoside reverse transcriptase inhibitor Drugs 0.000 description 1
- 231100000252 nontoxic Toxicity 0.000 description 1
- 230000003000 nontoxic effect Effects 0.000 description 1
- 235000005985 organic acids Nutrition 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- 229910052700 potassium Inorganic materials 0.000 description 1
- 239000011591 potassium Substances 0.000 description 1
- 239000001103 potassium chloride Substances 0.000 description 1
- 235000011164 potassium chloride Nutrition 0.000 description 1
- NNFCIKHAZHQZJG-UHFFFAOYSA-N potassium cyanide Chemical compound [K+].N#[C-] NNFCIKHAZHQZJG-UHFFFAOYSA-N 0.000 description 1
- 235000019260 propionic acid Nutrition 0.000 description 1
- 125000000714 pyrimidinyl group Chemical group 0.000 description 1
- 125000001453 quaternary ammonium group Chemical group 0.000 description 1
- IUVKMZGDUIUOCP-BTNSXGMBSA-N quinbolone Chemical compound O([C@H]1CC[C@H]2[C@H]3[C@@H]([C@]4(C=CC(=O)C=C4CC3)C)CC[C@@]21C)C1=CCCC1 IUVKMZGDUIUOCP-BTNSXGMBSA-N 0.000 description 1
- 229930195734 saturated hydrocarbon Natural products 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
- 239000011734 sodium Substances 0.000 description 1
- 239000011780 sodium chloride Substances 0.000 description 1
- 239000012453 solvate Substances 0.000 description 1
- 239000007858 starting material Substances 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000001117 sulphuric acid Substances 0.000 description 1
- 235000011149 sulphuric acid 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
- DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
- MCZDHTKJGDCTAE-UHFFFAOYSA-M tetrabutylazanium;acetate Chemical compound CC([O-])=O.CCCC[N+](CCCC)(CCCC)CCCC MCZDHTKJGDCTAE-UHFFFAOYSA-M 0.000 description 1
- KRRBFUJMQBDDPR-UHFFFAOYSA-N tetrabutylazanium;cyanide Chemical compound N#[C-].CCCC[N+](CCCC)(CCCC)CCCC KRRBFUJMQBDDPR-UHFFFAOYSA-N 0.000 description 1
- 231100000331 toxic Toxicity 0.000 description 1
- 230000002588 toxic effect Effects 0.000 description 1
Images
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
- C07D239/46—Two or more oxygen, sulphur or nitrogen atoms
- C07D239/47—One nitrogen atom and one oxygen or sulfur atom, e.g. cytosine
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- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (4)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| EP05104531.8 | 2005-05-26 | ||
| EP05104531 | 2005-05-26 | ||
| US68599305P | 2005-05-31 | 2005-05-31 | |
| US60/685,993 | 2005-05-31 |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| RU2007148968A RU2007148968A (ru) | 2009-07-10 |
| RU2458056C2 true RU2458056C2 (ru) | 2012-08-10 |
Family
ID=35822492
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| RU2007148968/04A RU2458056C2 (ru) | 2005-05-26 | 2006-05-24 | Способ получения 4-(1,6-дигидро-6-оксо-2-пиримидинил)амино-бензонитрила |
Country Status (19)
| Country | Link |
|---|---|
| US (2) | US8101752B2 (enExample) |
| EP (1) | EP1888537B1 (enExample) |
| JP (2) | JP5148483B2 (enExample) |
| CN (1) | CN101248051B (enExample) |
| AU (1) | AU2006251163C1 (enExample) |
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| IN2014DN04588A (enExample) * | 2005-05-26 | 2015-07-10 | Tibotec Pharm Ltd | |
| WO2012125993A1 (en) | 2011-03-17 | 2012-09-20 | Teva Pharmaceutical Industries Ltd. | Solid state forms of rilpivirine base, and rilipivirine salts |
| CN104321340B (zh) | 2012-03-13 | 2018-11-09 | 欧克塔医药公司 | 用于生产纤维蛋白原的改进工艺及其生产的纤维蛋白原 |
| CN103058936B (zh) * | 2013-01-23 | 2016-01-06 | 宁波九胜创新医药科技有限公司 | 4-[(4-氯-2-嘧啶基)氨基]苯腈的制备方法 |
| CN103193719B (zh) * | 2013-04-08 | 2015-07-22 | 宁波九胜创新医药科技有限公司 | 一种4-[(4-羟基-2-嘧啶基)氨基]苯腈的制备方法 |
| CN114933567B (zh) * | 2022-04-29 | 2023-07-11 | 武汉工程大学 | 一种2-甲硫基-4-嘧啶酮的制备方法 |
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| RU2037483C1 (ru) * | 1989-07-20 | 1995-06-19 | Мерк Патент Гмбх | Способ получения замещенных ароматических нитрилов |
| RU2108329C1 (ru) * | 1989-04-21 | 1998-04-10 | Зенека Лимитед | Производные четвертичного аминопиримидина и фармацевтическая композиция |
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| DE3923979A1 (de) | 1989-07-20 | 1991-01-24 | Merck Patent Gmbh | Verfahren zur herstellung von aromatischen nitrilen |
| ES2193660T3 (es) * | 1998-03-27 | 2003-11-01 | Janssen Pharmaceutica Nv | Derivados de pirimidina inhibidores de vih. |
| HRP20080359B1 (hr) * | 1998-11-10 | 2016-01-01 | Janssen Pharmaceutica N.V. | PIRIMIDINI KOJI INHIBIRAJU REPLIKACIJU HIV-a |
| AU775360B2 (en) * | 1999-09-24 | 2004-07-29 | Janssen Pharmaceutica N.V. | Antiviral compositions |
| WO2001085699A2 (en) * | 2000-05-08 | 2001-11-15 | Janssen Pharmaceutica N.V. | Prodrugs of hiv replication inhibiting pyrimidines |
| JO3429B1 (ar) * | 2001-08-13 | 2019-10-20 | Janssen Pharmaceutica Nv | مشتقات برميدينات مثبطة فيروس الايدز |
| NZ531853A (en) * | 2001-11-01 | 2006-02-24 | Janssen Pharmaceutica Nv | Heteroaryl amines as glycogen synthase kinase 3beta inhibitors (gsk3 inhibitors) |
| NZ538611A (en) * | 2002-08-09 | 2007-03-30 | Janssen Pharmaceutica Nv | Processes for the preparation of 4-[[4-[[4-(2-cyanoethenyl)-2,6-dimethylphenyl]amino]-2-pyrimidinyl]amino]benzonitrile |
| HRP20060126A2 (en) * | 2003-09-30 | 2008-05-31 | Janssen Pharmaceutica N.V. | Benzoimidazole compounds |
| IN2014DN04588A (enExample) * | 2005-05-26 | 2015-07-10 | Tibotec Pharm Ltd |
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| RU2108329C1 (ru) * | 1989-04-21 | 1998-04-10 | Зенека Лимитед | Производные четвертичного аминопиримидина и фармацевтическая композиция |
| RU2037483C1 (ru) * | 1989-07-20 | 1995-06-19 | Мерк Патент Гмбх | Способ получения замещенных ароматических нитрилов |
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|---|---|
| ME01612B (me) | 2014-09-20 |
| JP5580385B2 (ja) | 2014-08-27 |
| BRPI0611038B8 (pt) | 2022-10-25 |
| CA2609716A1 (en) | 2006-11-30 |
| WO2006125809A1 (en) | 2006-11-30 |
| US20120083606A1 (en) | 2012-04-05 |
| RU2007148968A (ru) | 2009-07-10 |
| BRPI0611038B1 (pt) | 2022-02-08 |
| CN101248051B (zh) | 2013-07-17 |
| JP2008545680A (ja) | 2008-12-18 |
| EP1888537B1 (en) | 2013-09-11 |
| PT1888537E (pt) | 2013-11-26 |
| BRPI0611038A2 (pt) | 2010-08-10 |
| MX2007014881A (es) | 2008-02-15 |
| IN2014DN04588A (enExample) | 2015-07-10 |
| RS53062B (sr) | 2014-04-30 |
| US20080171878A1 (en) | 2008-07-17 |
| AU2006251163A1 (en) | 2006-11-30 |
| EP1888537A1 (en) | 2008-02-20 |
| ES2437202T3 (es) | 2014-01-09 |
| PL1888537T3 (pl) | 2014-02-28 |
| SI1888537T1 (sl) | 2014-01-31 |
| JP5148483B2 (ja) | 2013-02-20 |
| AU2006251163C1 (en) | 2012-07-12 |
| DK1888537T3 (da) | 2013-12-09 |
| CN101248051A (zh) | 2008-08-20 |
| HK1123551A1 (en) | 2009-06-19 |
| US8618291B2 (en) | 2013-12-31 |
| AU2006251163B2 (en) | 2012-03-08 |
| HRP20131133T1 (hr) | 2014-01-03 |
| US8101752B2 (en) | 2012-01-24 |
| JP2013040194A (ja) | 2013-02-28 |
| CA2609716C (en) | 2014-10-14 |
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