AU2019348974A1 - Synthetic methodfor the preparation of an alkoxymethylene-benzoylacetonitrile - Google Patents
Synthetic methodfor the preparation of an alkoxymethylene-benzoylacetonitrile Download PDFInfo
- Publication number
- AU2019348974A1 AU2019348974A1 AU2019348974A AU2019348974A AU2019348974A1 AU 2019348974 A1 AU2019348974 A1 AU 2019348974A1 AU 2019348974 A AU2019348974 A AU 2019348974A AU 2019348974 A AU2019348974 A AU 2019348974A AU 2019348974 A1 AU2019348974 A1 AU 2019348974A1
- Authority
- AU
- Australia
- Prior art keywords
- compound
- formula
- orthoformate
- reaction mass
- reaction
- Prior art date
- Legal status (The legal status 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 status listed.)
- Abandoned
Links
- 238000002360 preparation method Methods 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 74
- 238000000034 method Methods 0.000 claims abstract description 74
- VGUSQKZDZHAAEE-UHFFFAOYSA-N 3-[5-amino-4-(3-cyanobenzoyl)pyrazol-1-yl]-n-cyclopropyl-4-methylbenzamide Chemical compound CC1=CC=C(C(=O)NC2CC2)C=C1N(C=1N)N=CC=1C(=O)C1=CC=CC(C#N)=C1 VGUSQKZDZHAAEE-UHFFFAOYSA-N 0.000 claims abstract description 26
- 150000003839 salts Chemical class 0.000 claims abstract description 25
- 229940125782 compound 2 Drugs 0.000 claims abstract description 22
- 239000012453 solvate Substances 0.000 claims abstract description 22
- 238000004519 manufacturing process Methods 0.000 claims abstract description 21
- 229940125904 compound 1 Drugs 0.000 claims abstract description 15
- 238000003786 synthesis reaction Methods 0.000 claims abstract description 14
- 230000015572 biosynthetic process Effects 0.000 claims abstract description 12
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 6
- 238000006243 chemical reaction Methods 0.000 claims description 103
- 239000000047 product Substances 0.000 claims description 28
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 25
- 239000000706 filtrate Substances 0.000 claims description 20
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 18
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 claims description 14
- GKASDNZWUGIAMG-UHFFFAOYSA-N triethyl orthoformate Chemical compound CCOC(OCC)OCC GKASDNZWUGIAMG-UHFFFAOYSA-N 0.000 claims description 12
- 238000001914 filtration Methods 0.000 claims description 11
- 238000005406 washing Methods 0.000 claims description 11
- 239000000010 aprotic solvent Substances 0.000 claims description 10
- 238000001816 cooling Methods 0.000 claims description 10
- 239000012296 anti-solvent Substances 0.000 claims description 9
- 238000001035 drying Methods 0.000 claims description 9
- 238000004821 distillation Methods 0.000 claims description 8
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 claims description 7
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 claims description 6
- 150000007524 organic acids Chemical class 0.000 claims description 5
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 claims description 4
- PYOKUURKVVELLB-UHFFFAOYSA-N trimethyl orthoformate Chemical compound COC(OC)OC PYOKUURKVVELLB-UHFFFAOYSA-N 0.000 claims description 4
- 125000006527 (C1-C5) alkyl group Chemical group 0.000 claims description 2
- SGJBIFUEFLWXJY-UHFFFAOYSA-N 1-(dibutoxymethoxy)butane Chemical compound CCCCOC(OCCCC)OCCCC SGJBIFUEFLWXJY-UHFFFAOYSA-N 0.000 claims description 2
- NRRGKWUTVHJHCS-UHFFFAOYSA-N 1-(dipentoxymethoxy)pentane Chemical compound CCCCCOC(OCCCCC)OCCCCC NRRGKWUTVHJHCS-UHFFFAOYSA-N 0.000 claims description 2
- RWNXXQFJBALKAX-UHFFFAOYSA-N 1-(dipropoxymethoxy)propane Chemical compound CCCOC(OCCC)OCCC RWNXXQFJBALKAX-UHFFFAOYSA-N 0.000 claims description 2
- CTQNGGLPUBDAKN-UHFFFAOYSA-N O-Xylene Chemical compound CC1=CC=CC=C1C CTQNGGLPUBDAKN-UHFFFAOYSA-N 0.000 claims description 2
- BVQHHUQLZPXYAQ-UHFFFAOYSA-N acetyl butanoate Chemical compound CCCC(=O)OC(C)=O BVQHHUQLZPXYAQ-UHFFFAOYSA-N 0.000 claims description 2
- KLUDQUOLAFVLOL-UHFFFAOYSA-N acetyl propanoate Chemical compound CCC(=O)OC(C)=O KLUDQUOLAFVLOL-UHFFFAOYSA-N 0.000 claims description 2
- YHASWHZGWUONAO-UHFFFAOYSA-N butanoyl butanoate Chemical compound CCCC(=O)OC(=O)CCC YHASWHZGWUONAO-UHFFFAOYSA-N 0.000 claims description 2
- WYVAMUWZEOHJOQ-UHFFFAOYSA-N propionic anhydride Chemical compound CCC(=O)OC(=O)CC WYVAMUWZEOHJOQ-UHFFFAOYSA-N 0.000 claims description 2
- 239000008096 xylene Substances 0.000 claims description 2
- ABRVLXLNVJHDRQ-UHFFFAOYSA-N [2-pyridin-3-yl-6-(trifluoromethyl)pyridin-4-yl]methanamine Chemical compound FC(C1=CC(=CC(=N1)C=1C=NC=CC=1)CN)(F)F ABRVLXLNVJHDRQ-UHFFFAOYSA-N 0.000 claims 1
- 229940126214 compound 3 Drugs 0.000 description 51
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 47
- 229940125898 compound 5 Drugs 0.000 description 36
- 239000006227 byproduct Substances 0.000 description 33
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 29
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 28
- 239000000203 mixture Substances 0.000 description 25
- 150000002826 nitrites Chemical class 0.000 description 16
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 description 13
- -1 ethanol Chemical compound 0.000 description 13
- 239000011593 sulfur Substances 0.000 description 13
- 229910052717 sulfur Inorganic materials 0.000 description 13
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 12
- 239000012043 crude product Substances 0.000 description 12
- 238000000746 purification Methods 0.000 description 10
- LPXPTNMVRIOKMN-UHFFFAOYSA-M sodium nitrite Chemical compound [Na+].[O-]N=O LPXPTNMVRIOKMN-UHFFFAOYSA-M 0.000 description 10
- GEHJYWRUCIMESM-UHFFFAOYSA-L sodium sulfite Chemical compound [Na+].[Na+].[O-]S([O-])=O GEHJYWRUCIMESM-UHFFFAOYSA-L 0.000 description 8
- WTKZEGDFNFYCGP-UHFFFAOYSA-N Pyrazole Chemical compound C=1C=NNC=1 WTKZEGDFNFYCGP-UHFFFAOYSA-N 0.000 description 7
- LSNNMFCWUKXFEE-UHFFFAOYSA-N Sulfurous acid Chemical compound OS(O)=O LSNNMFCWUKXFEE-UHFFFAOYSA-N 0.000 description 7
- 239000003638 chemical reducing agent Substances 0.000 description 7
- DSGOECBBNQENSY-UHFFFAOYSA-N 3-[5-amino-4-(3-cyanobenzoyl)pyrazol-1-yl]-4-methylbenzoic acid Chemical compound NC1=C(C=NN1C=1C=C(C(=O)O)C=CC=1C)C(C1=CC(=CC=C1)C#N)=O DSGOECBBNQENSY-UHFFFAOYSA-N 0.000 description 6
- HTJDQJBWANPRPF-UHFFFAOYSA-N Cyclopropylamine Chemical compound NC1CC1 HTJDQJBWANPRPF-UHFFFAOYSA-N 0.000 description 6
- JFDZBHWFFUWGJE-UHFFFAOYSA-N benzonitrile Chemical compound N#CC1=CC=CC=C1 JFDZBHWFFUWGJE-UHFFFAOYSA-N 0.000 description 6
- PFKFTWBEEFSNDU-UHFFFAOYSA-N carbonyldiimidazole Chemical compound C1=CN=CN1C(=O)N1C=CN=C1 PFKFTWBEEFSNDU-UHFFFAOYSA-N 0.000 description 6
- 239000012954 diazonium Substances 0.000 description 6
- 150000001989 diazonium salts Chemical class 0.000 description 6
- 230000008030 elimination Effects 0.000 description 6
- 238000003379 elimination reaction Methods 0.000 description 6
- 238000004128 high performance liquid chromatography Methods 0.000 description 6
- 239000012535 impurity Substances 0.000 description 6
- 239000003880 polar aprotic solvent Substances 0.000 description 6
- ZGBJBMJUVJUNAZ-UHFFFAOYSA-N 3-(2-cyano-3-ethoxyprop-2-enoyl)benzonitrile Chemical compound C(#N)C(C(=O)C=1C=C(C#N)C=CC=1)=COCC ZGBJBMJUVJUNAZ-UHFFFAOYSA-N 0.000 description 5
- UKPYFYWYQILFOM-UHFFFAOYSA-N 3-hydrazinyl-4-methylbenzoic acid Chemical compound CC1=CC=C(C(O)=O)C=C1NN UKPYFYWYQILFOM-UHFFFAOYSA-N 0.000 description 5
- 239000002253 acid Substances 0.000 description 5
- 239000003153 chemical reaction reagent Substances 0.000 description 5
- 229910052500 inorganic mineral Inorganic materials 0.000 description 5
- 239000011707 mineral Substances 0.000 description 5
- 235000010288 sodium nitrite Nutrition 0.000 description 5
- 239000000725 suspension Substances 0.000 description 5
- XKFIFYROMAAUDL-UHFFFAOYSA-N 3-amino-4-methylbenzoic acid Chemical compound CC1=CC=C(C(O)=O)C=C1N XKFIFYROMAAUDL-UHFFFAOYSA-N 0.000 description 4
- PAYRUJLWNCNPSJ-UHFFFAOYSA-N Aniline Chemical compound NC1=CC=CC=C1 PAYRUJLWNCNPSJ-UHFFFAOYSA-N 0.000 description 4
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 4
- IOVCWXUNBOPUCH-UHFFFAOYSA-M Nitrite anion Chemical compound [O-]N=O IOVCWXUNBOPUCH-UHFFFAOYSA-M 0.000 description 4
- 229910052783 alkali metal Inorganic materials 0.000 description 4
- 229910052784 alkaline earth metal Inorganic materials 0.000 description 4
- 239000000463 material Substances 0.000 description 4
- 150000003217 pyrazoles Chemical class 0.000 description 4
- 235000010265 sodium sulphite Nutrition 0.000 description 4
- 239000002699 waste material Substances 0.000 description 4
- TXUICONDJPYNPY-UHFFFAOYSA-N (1,10,13-trimethyl-3-oxo-4,5,6,7,8,9,11,12,14,15,16,17-dodecahydrocyclopenta[a]phenanthren-17-yl) heptanoate Chemical compound C1CC2CC(=O)C=C(C)C2(C)C2C1C1CCC(OC(=O)CCCCCC)C1(C)CC2 TXUICONDJPYNPY-UHFFFAOYSA-N 0.000 description 3
- XXUNIGZDNWWYED-UHFFFAOYSA-N 2-methylbenzamide Chemical compound CC1=CC=CC=C1C(N)=O XXUNIGZDNWWYED-UHFFFAOYSA-N 0.000 description 3
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 3
- 208000034809 Product contamination Diseases 0.000 description 3
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 3
- 239000012467 final product Substances 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 230000003301 hydrolyzing effect Effects 0.000 description 3
- 238000002156 mixing Methods 0.000 description 3
- 239000007787 solid Substances 0.000 description 3
- 239000002904 solvent Substances 0.000 description 3
- 239000001119 stannous chloride Substances 0.000 description 3
- 235000011150 stannous chloride Nutrition 0.000 description 3
- 239000007858 starting material Substances 0.000 description 3
- 231100000583 toxicological profile Toxicity 0.000 description 3
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
- ATJFFYVFTNAWJD-UHFFFAOYSA-N Tin Chemical compound [Sn] ATJFFYVFTNAWJD-UHFFFAOYSA-N 0.000 description 2
- 125000000218 acetic acid group Chemical group C(C)(=O)* 0.000 description 2
- 125000002252 acyl group Chemical group 0.000 description 2
- 150000001448 anilines Chemical class 0.000 description 2
- 238000011109 contamination Methods 0.000 description 2
- 208000012839 conversion disease Diseases 0.000 description 2
- 239000007822 coupling agent Substances 0.000 description 2
- GRWZHXKQBITJKP-UHFFFAOYSA-L dithionite(2-) Chemical class [O-]S(=O)S([O-])=O GRWZHXKQBITJKP-UHFFFAOYSA-L 0.000 description 2
- 125000003720 ethoxymethylidene group Chemical group [H]C(=*)OC([H])([H])C([H])([H])[H] 0.000 description 2
- 150000002429 hydrazines Chemical class 0.000 description 2
- 102000002574 p38 Mitogen-Activated Protein Kinases Human genes 0.000 description 2
- 238000001953 recrystallisation Methods 0.000 description 2
- 238000010992 reflux Methods 0.000 description 2
- 125000003944 tolyl group Chemical group 0.000 description 2
- 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 2
- ACVAUFCPHXVLQA-UHFFFAOYSA-N 1h-imidazole;1h-pyrazole Chemical compound C=1C=NNC=1.C1=CNC=N1 ACVAUFCPHXVLQA-UHFFFAOYSA-N 0.000 description 1
- CWULKMSXLFIFKW-UHFFFAOYSA-N 3-(2-cyanoacetyl)benzonitrile Chemical compound N#CCC(=O)C1=CC=CC(C#N)=C1 CWULKMSXLFIFKW-UHFFFAOYSA-N 0.000 description 1
- JQJPBYFTQAANLE-UHFFFAOYSA-N Butyl nitrite Chemical compound CCCCON=O JQJPBYFTQAANLE-UHFFFAOYSA-N 0.000 description 1
- 208000006545 Chronic Obstructive Pulmonary Disease Diseases 0.000 description 1
- 102000004127 Cytokines Human genes 0.000 description 1
- 108090000695 Cytokines Proteins 0.000 description 1
- 101100291385 Drosophila melanogaster p38a gene Proteins 0.000 description 1
- QQZWEECEMNQSTG-UHFFFAOYSA-N Ethyl nitrite Chemical compound CCON=O QQZWEECEMNQSTG-UHFFFAOYSA-N 0.000 description 1
- 239000007821 HATU Substances 0.000 description 1
- 229910004039 HBF4 Inorganic materials 0.000 description 1
- 238000003109 Karl Fischer titration Methods 0.000 description 1
- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 1
- OAICVXFJPJFONN-UHFFFAOYSA-N Phosphorus Chemical compound [P] OAICVXFJPJFONN-UHFFFAOYSA-N 0.000 description 1
- 102000001253 Protein Kinase Human genes 0.000 description 1
- FYDGRHCYVIUOSL-UHFFFAOYSA-L S(=O)([O-])[O-].[Ag+2] Chemical compound S(=O)([O-])[O-].[Ag+2] FYDGRHCYVIUOSL-UHFFFAOYSA-L 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- DWAQJAXMDSEUJJ-UHFFFAOYSA-M Sodium bisulfite Chemical compound [Na+].OS([O-])=O DWAQJAXMDSEUJJ-UHFFFAOYSA-M 0.000 description 1
- AZFNGPAYDKGCRB-XCPIVNJJSA-M [(1s,2s)-2-amino-1,2-diphenylethyl]-(4-methylphenyl)sulfonylazanide;chlororuthenium(1+);1-methyl-4-propan-2-ylbenzene Chemical compound [Ru+]Cl.CC(C)C1=CC=C(C)C=C1.C1=CC(C)=CC=C1S(=O)(=O)[N-][C@@H](C=1C=CC=CC=1)[C@@H](N)C1=CC=CC=C1 AZFNGPAYDKGCRB-XCPIVNJJSA-M 0.000 description 1
- 150000008064 anhydrides Chemical class 0.000 description 1
- 238000003556 assay Methods 0.000 description 1
- 125000004429 atom Chemical group 0.000 description 1
- LVGQIQHJMRUCRM-UHFFFAOYSA-L calcium bisulfite Chemical compound [Ca+2].OS([O-])=O.OS([O-])=O LVGQIQHJMRUCRM-UHFFFAOYSA-L 0.000 description 1
- 235000010260 calcium hydrogen sulphite Nutrition 0.000 description 1
- GBAOBIBJACZTNA-UHFFFAOYSA-L calcium sulfite Chemical compound [Ca+2].[O-]S([O-])=O GBAOBIBJACZTNA-UHFFFAOYSA-L 0.000 description 1
- 235000010261 calcium sulphite Nutrition 0.000 description 1
- 238000004587 chromatography analysis Methods 0.000 description 1
- 230000008878 coupling Effects 0.000 description 1
- 238000010168 coupling process Methods 0.000 description 1
- 238000005859 coupling reaction Methods 0.000 description 1
- 239000013078 crystal Substances 0.000 description 1
- 238000002425 crystallisation Methods 0.000 description 1
- 230000008025 crystallization Effects 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- BBLSYMNDKUHQAG-UHFFFAOYSA-L dilithium;sulfite Chemical compound [Li+].[Li+].[O-]S([O-])=O BBLSYMNDKUHQAG-UHFFFAOYSA-L 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000012851 eutrophication Methods 0.000 description 1
- 239000012065 filter cake Substances 0.000 description 1
- 229910052739 hydrogen Inorganic materials 0.000 description 1
- 239000001257 hydrogen Substances 0.000 description 1
- 230000007062 hydrolysis Effects 0.000 description 1
- 238000006460 hydrolysis reaction Methods 0.000 description 1
- NPZTUJOABDZTLV-UHFFFAOYSA-N hydroxybenzotriazole Substances O=C1C=CC=C2NNN=C12 NPZTUJOABDZTLV-UHFFFAOYSA-N 0.000 description 1
- 230000002401 inhibitory effect Effects 0.000 description 1
- 238000002955 isolation Methods 0.000 description 1
- 229940043355 kinase inhibitor Drugs 0.000 description 1
- 238000011031 large-scale manufacturing process Methods 0.000 description 1
- IDNHOWMYUQKKTI-UHFFFAOYSA-M lithium nitrite Chemical compound [Li+].[O-]N=O IDNHOWMYUQKKTI-UHFFFAOYSA-M 0.000 description 1
- AAJBNRZDTJPMTJ-UHFFFAOYSA-L magnesium;dinitrite Chemical compound [Mg+2].[O-]N=O.[O-]N=O AAJBNRZDTJPMTJ-UHFFFAOYSA-L 0.000 description 1
- JESHZQPNPCJVNG-UHFFFAOYSA-L magnesium;sulfite Chemical compound [Mg+2].[O-]S([O-])=O JESHZQPNPCJVNG-UHFFFAOYSA-L 0.000 description 1
- 238000005374 membrane filtration Methods 0.000 description 1
- CSDTZUBPSYWZDX-UHFFFAOYSA-N n-pentyl nitrite Chemical compound CCCCCON=O CSDTZUBPSYWZDX-UHFFFAOYSA-N 0.000 description 1
- 150000002823 nitrates Chemical class 0.000 description 1
- 238000005580 one pot reaction Methods 0.000 description 1
- 150000002894 organic compounds Chemical class 0.000 description 1
- AICOOMRHRUFYCM-ZRRPKQBOSA-N oxazine, 1 Chemical compound C([C@@H]1[C@H](C(C[C@]2(C)[C@@H]([C@H](C)N(C)C)[C@H](O)C[C@]21C)=O)CC1=CC2)C[C@H]1[C@@]1(C)[C@H]2N=C(C(C)C)OC1 AICOOMRHRUFYCM-ZRRPKQBOSA-N 0.000 description 1
- 125000004430 oxygen atom Chemical group O* 0.000 description 1
- RAFRTSDUWORDLA-UHFFFAOYSA-N phenyl 3-chloropropanoate Chemical compound ClCCC(=O)OC1=CC=CC=C1 RAFRTSDUWORDLA-UHFFFAOYSA-N 0.000 description 1
- 239000011574 phosphorus Substances 0.000 description 1
- 229910052698 phosphorus Inorganic materials 0.000 description 1
- 239000003757 phosphotransferase inhibitor Substances 0.000 description 1
- DJEHXEMURTVAOE-UHFFFAOYSA-M potassium bisulfite Chemical compound [K+].OS([O-])=O DJEHXEMURTVAOE-UHFFFAOYSA-M 0.000 description 1
- 229940099427 potassium bisulfite Drugs 0.000 description 1
- 235000010259 potassium hydrogen sulphite Nutrition 0.000 description 1
- 235000010289 potassium nitrite Nutrition 0.000 description 1
- 239000004304 potassium nitrite Substances 0.000 description 1
- BHZRJJOHZFYXTO-UHFFFAOYSA-L potassium sulfite Chemical compound [K+].[K+].[O-]S([O-])=O BHZRJJOHZFYXTO-UHFFFAOYSA-L 0.000 description 1
- 235000019252 potassium sulphite Nutrition 0.000 description 1
- 238000002953 preparative HPLC Methods 0.000 description 1
- KAOQVXHBVNKNHA-UHFFFAOYSA-N propyl nitrite Chemical compound CCCON=O KAOQVXHBVNKNHA-UHFFFAOYSA-N 0.000 description 1
- 108060006633 protein kinase Proteins 0.000 description 1
- 238000010926 purge Methods 0.000 description 1
- 239000011541 reaction mixture Substances 0.000 description 1
- 238000004366 reverse phase liquid chromatography Methods 0.000 description 1
- 238000013341 scale-up Methods 0.000 description 1
- 239000000741 silica gel Substances 0.000 description 1
- 229910002027 silica gel Inorganic materials 0.000 description 1
- KKKDGYXNGYJJRX-UHFFFAOYSA-M silver nitrite Chemical compound [Ag+].[O-]N=O KKKDGYXNGYJJRX-UHFFFAOYSA-M 0.000 description 1
- JVBXVOWTABLYPX-UHFFFAOYSA-L sodium dithionite Chemical group [Na+].[Na+].[O-]S(=O)S([O-])=O JVBXVOWTABLYPX-UHFFFAOYSA-L 0.000 description 1
- 235000010267 sodium hydrogen sulphite Nutrition 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006257 total synthesis reaction Methods 0.000 description 1
- 238000001665 trituration Methods 0.000 description 1
- 238000010626 work up procedure Methods 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/30—Preparation of carboxylic acid nitriles by reactions not involving the formation of cyano groups
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D3/00—Distillation or related exchange processes in which liquids are contacted with gaseous media, e.g. stripping
- B01D3/009—Distillation or related exchange processes in which liquids are contacted with gaseous media, e.g. stripping in combination with chemical reactions
-
- B—PERFORMING OPERATIONS; TRANSPORTING
- B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
- B01D—SEPARATION
- B01D3/00—Distillation or related exchange processes in which liquids are contacted with gaseous media, e.g. stripping
- B01D3/10—Vacuum distillation
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C253/00—Preparation of carboxylic acid nitriles
- C07C253/32—Separation; Purification; Stabilisation; Use of additives
- C07C253/34—Separation; Purification
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C255/00—Carboxylic acid nitriles
- C07C255/49—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton
- C07C255/54—Carboxylic acid nitriles having cyano groups bound to carbon atoms of six-membered aromatic rings of a carbon skeleton containing cyano groups and etherified hydroxy groups bound to the carbon skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D231/00—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings
- C07D231/02—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings
- C07D231/10—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole rings not condensed with other rings having two or three double bonds between ring members or between ring members and non-ring members
- C07D231/14—Heterocyclic compounds containing 1,2-diazole or hydrogenated 1,2-diazole 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
- C07D231/38—Nitrogen atoms
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Chemical Kinetics & Catalysis (AREA)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1815699.2A GB201815699D0 (en) | 2018-09-26 | 2018-09-26 | Synthetic method |
| GB1815699.2 | 2018-09-26 | ||
| PCT/GB2019/052720 WO2020065325A1 (en) | 2018-09-26 | 2019-09-26 | Synthetic methodfor the preparation of an alkoxymethylene-benzoylacetonitrile |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| AU2019348974A1 true AU2019348974A1 (en) | 2021-04-22 |
Family
ID=64024259
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| AU2019348974A Abandoned AU2019348974A1 (en) | 2018-09-26 | 2019-09-26 | Synthetic methodfor the preparation of an alkoxymethylene-benzoylacetonitrile |
Country Status (12)
| Country | Link |
|---|---|
| US (1) | US20220033352A1 (https=) |
| EP (1) | EP3856712B1 (https=) |
| JP (1) | JP2022502413A (https=) |
| KR (1) | KR20210065110A (https=) |
| CN (1) | CN112805269A (https=) |
| AU (1) | AU2019348974A1 (https=) |
| CA (1) | CA3113000A1 (https=) |
| DK (1) | DK3856712T3 (https=) |
| ES (1) | ES2933687T3 (https=) |
| GB (1) | GB201815699D0 (https=) |
| IL (1) | IL281635A (https=) |
| WO (1) | WO2020065325A1 (https=) |
Family Cites Families (5)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DE1809386A1 (de) * | 1968-11-16 | 1970-06-11 | Bayer Ag | Verfahren zur Herstellung von 1,5-disubstituierten 4-Cyanopyrazolen |
| JPS62174055A (ja) * | 1985-10-01 | 1987-07-30 | Kanebo Ltd | 新規キノリンカルボン酸誘導体および該化合物を有効成分とする抗菌剤 |
| US4686221A (en) * | 1985-10-01 | 1987-08-11 | Kanebo, Ltd. | Quinolinecarboxylic acid compounds and antimicrobial agent containing the same |
| CA2329065A1 (en) * | 1998-05-05 | 1999-11-11 | Francisco Xavier Talamas | Pyrazole derivatives as p-38 map kinase inhibitors |
| KR101120857B1 (ko) | 2003-06-26 | 2012-04-12 | 노파르티스 아게 | 5원의 헤테로사이클-기재 ｐ38 키나제 억제제 |
-
2018
- 2018-09-26 GB GBGB1815699.2A patent/GB201815699D0/en not_active Ceased
-
2019
- 2019-09-26 EP EP19780307.5A patent/EP3856712B1/en active Active
- 2019-09-26 ES ES19780307T patent/ES2933687T3/es active Active
- 2019-09-26 JP JP2021516981A patent/JP2022502413A/ja not_active Ceased
- 2019-09-26 CA CA3113000A patent/CA3113000A1/en active Pending
- 2019-09-26 WO PCT/GB2019/052720 patent/WO2020065325A1/en not_active Ceased
- 2019-09-26 CN CN201980063103.3A patent/CN112805269A/zh active Pending
- 2019-09-26 DK DK19780307.5T patent/DK3856712T3/da active
- 2019-09-26 AU AU2019348974A patent/AU2019348974A1/en not_active Abandoned
- 2019-09-26 KR KR1020217008900A patent/KR20210065110A/ko not_active Ceased
- 2019-09-26 US US17/279,326 patent/US20220033352A1/en not_active Abandoned
-
2021
- 2021-03-18 IL IL281635A patent/IL281635A/en unknown
Also Published As
| Publication number | Publication date |
|---|---|
| WO2020065325A1 (en) | 2020-04-02 |
| CN112805269A (zh) | 2021-05-14 |
| DK3856712T3 (da) | 2022-12-12 |
| CA3113000A1 (en) | 2020-04-02 |
| IL281635A (en) | 2021-05-31 |
| KR20210065110A (ko) | 2021-06-03 |
| EP3856712B1 (en) | 2022-10-26 |
| ES2933687T3 (es) | 2023-02-13 |
| JP2022502413A (ja) | 2022-01-11 |
| GB201815699D0 (en) | 2018-11-07 |
| US20220033352A1 (en) | 2022-02-03 |
| EP3856712A1 (en) | 2021-08-04 |
Similar Documents
| Publication | Publication Date | Title |
|---|---|---|
| EP3856721B1 (en) | Synthetic method for the preparation of a 3-[5-amino-4-(3-cyanobenzoyl)-pyrazol compound | |
| EP3856711B1 (en) | Synthetic method for the preparation of an hydrazine compound | |
| EP3856712B1 (en) | Synthetic methodfor the preparation of an alkoxymethylene-benzoylacetonitrile | |
| HK40049030B (en) | Synthetic method for the preparation of a 3-[5-amino-4-(3-cyanobenzoyl)-pyrazol compound | |
| HK40049030A (en) | Synthetic method for the preparation of a 3-[5-amino-4-(3-cyanobenzoyl)-pyrazol compound | |
| JP2013006782A (ja) | ピラゾール化合物の製造方法 | |
| JP2717995B2 (ja) | １，２，３−トリアゾールの製法 | |
| KR900001081B1 (ko) | 4-아실-5-피라졸릴 4-톨루엔 술포네이트 유도체의 제법 | |
| JP4267943B2 (ja) | ３−アミノ−４−置換−５−ピラゾロン類の製造方法 | |
| JP2010077070A (ja) | イミダゾール誘導体の精製方法 | |
| JPH08277251A (ja) | ジメチルホルムアミドジメチルアセタールの製造方法 | |
| JP2000344742A (ja) | ３−アミノ−１−フェニルピロリジン−２−オン誘導体の製造方法 | |
| JP2005247727A (ja) | 高純度５−ヒドロキシキノリン | |
| JPH051038A (ja) | ピラゾール誘導体の製造方法 |
Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| MK1 | Application lapsed section 142(2)(a) - no request for examination in relevant period |