CA2910971A1 - Synthesis of 3-(5-amino-2-methyl-4-oxoquinazolin-3(4h)-yl)piperidine-2,6-dione - Google Patents
Synthesis of 3-(5-amino-2-methyl-4-oxoquinazolin-3(4h)-yl)piperidine-2,6-dioneInfo
- Publication number
- CA2910971A1 CA2910971A1 CA2910971A CA2910971A CA2910971A1 CA 2910971 A1 CA2910971 A1 CA 2910971A1 CA 2910971 A CA2910971 A CA 2910971A CA 2910971 A CA2910971 A CA 2910971A CA 2910971 A1 CA2910971 A1 CA 2910971A1
- Authority
- CA
- Canada
- Prior art keywords
- dione
- methyl
- piperidine
- oxoquinazolin
- nitro
- 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
- RSNPAKAFCAAMBH-UHFFFAOYSA-N 3-(5-amino-2-methyl-4-oxoquinazolin-3-yl)piperidine-2,6-dione Chemical compound CC1=NC2=CC=CC(N)=C2C(=O)N1C1CCC(=O)NC1=O RSNPAKAFCAAMBH-UHFFFAOYSA-N 0.000 title claims abstract 13
- 230000015572 biosynthetic process Effects 0.000 title description 2
- 238000003786 synthesis reaction Methods 0.000 title description 2
- 239000000203 mixture Substances 0.000 claims abstract description 111
- 238000000034 method Methods 0.000 claims abstract description 109
- 150000003839 salts Chemical class 0.000 claims abstract description 99
- HBAQYPYDRFILMT-UHFFFAOYSA-N 8-[3-(1-cyclopropylpyrazol-4-yl)-1H-pyrazolo[4,3-d]pyrimidin-5-yl]-3-methyl-3,8-diazabicyclo[3.2.1]octan-2-one Chemical class C1(CC1)N1N=CC(=C1)C1=NNC2=C1N=C(N=C2)N1C2C(N(CC1CC2)C)=O HBAQYPYDRFILMT-UHFFFAOYSA-N 0.000 claims abstract description 64
- BDAGIHXWWSANSR-UHFFFAOYSA-N methanoic acid Natural products OC=O BDAGIHXWWSANSR-UHFFFAOYSA-N 0.000 claims description 128
- 239000002904 solvent Substances 0.000 claims description 103
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 102
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 claims description 75
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims description 70
- 239000012453 solvate Substances 0.000 claims description 67
- -1 C2-14 alkene Chemical class 0.000 claims description 65
- OSWFIVFLDKOXQC-UHFFFAOYSA-N 4-(3-methoxyphenyl)aniline Chemical compound COC1=CC=CC(C=2C=CC(N)=CC=2)=C1 OSWFIVFLDKOXQC-UHFFFAOYSA-N 0.000 claims description 64
- 235000019253 formic acid Nutrition 0.000 claims description 64
- 239000003054 catalyst Substances 0.000 claims description 62
- 229940013688 formic acid Drugs 0.000 claims description 59
- WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 51
- NPWMTBZSRRLQNJ-UHFFFAOYSA-N pyroglutamine Chemical compound NC1CCC(=O)NC1=O NPWMTBZSRRLQNJ-UHFFFAOYSA-N 0.000 claims description 48
- 239000003153 chemical reaction reagent Substances 0.000 claims description 45
- 239000000852 hydrogen donor Substances 0.000 claims description 45
- 150000001242 acetic acid derivatives Chemical class 0.000 claims description 44
- KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical group [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims description 43
- GGKYLHNARFFORH-UHFFFAOYSA-N 2-amino-6-nitrobenzoic acid Chemical compound NC1=CC=CC([N+]([O-])=O)=C1C(O)=O GGKYLHNARFFORH-UHFFFAOYSA-N 0.000 claims description 42
- 125000000623 heterocyclic group Chemical group 0.000 claims description 40
- 125000001424 substituent group Chemical group 0.000 claims description 38
- 238000009901 transfer hydrogenation reaction Methods 0.000 claims description 36
- 230000008878 coupling Effects 0.000 claims description 35
- 238000010168 coupling process Methods 0.000 claims description 35
- 238000005859 coupling reaction Methods 0.000 claims description 35
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical group OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 claims description 30
- 150000001732 carboxylic acid derivatives Chemical class 0.000 claims description 30
- 125000001072 heteroaryl group Chemical group 0.000 claims description 28
- MMJSZIMFGHOSBC-UHFFFAOYSA-N 2-methyl-5-nitro-3,1-benzoxazin-4-one Chemical compound C1=CC([N+]([O-])=O)=C2C(=O)OC(C)=NC2=C1 MMJSZIMFGHOSBC-UHFFFAOYSA-N 0.000 claims description 27
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 claims description 23
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 22
- CXWXQJXEFPUFDZ-UHFFFAOYSA-N tetralin Chemical compound C1=CC=C2CCCCC2=C1 CXWXQJXEFPUFDZ-UHFFFAOYSA-N 0.000 claims description 20
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 claims description 19
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 18
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 claims description 18
- 238000006243 chemical reaction Methods 0.000 claims description 17
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 claims description 16
- 239000012535 impurity Substances 0.000 claims description 16
- 150000001733 carboxylic acid esters Chemical class 0.000 claims description 15
- RAXXELZNTBOGNW-UHFFFAOYSA-N imidazole Natural products C1=CNC=N1 RAXXELZNTBOGNW-UHFFFAOYSA-N 0.000 claims description 15
- PAQZWJGSJMLPMG-UHFFFAOYSA-N 2,4,6-tripropyl-1,3,5,2$l^{5},4$l^{5},6$l^{5}-trioxatriphosphinane 2,4,6-trioxide Chemical compound CCCP1(=O)OP(=O)(CCC)OP(=O)(CCC)O1 PAQZWJGSJMLPMG-UHFFFAOYSA-N 0.000 claims description 13
- CTMHWPIWNRWQEG-UHFFFAOYSA-N 1-methylcyclohexene Chemical compound CC1=CCCCC1 CTMHWPIWNRWQEG-UHFFFAOYSA-N 0.000 claims description 12
- HGCIXCUEYOPUTN-UHFFFAOYSA-N cyclohexene Chemical compound C1CCC=CC1 HGCIXCUEYOPUTN-UHFFFAOYSA-N 0.000 claims description 12
- 150000002390 heteroarenes Chemical class 0.000 claims description 11
- KHEXQYOPAOPUQQ-UHFFFAOYSA-N 3-(2-methyl-5-nitro-4-oxoquinazolin-3-yl)piperidine-2,6-dione Chemical compound CC1=NC2=CC=CC([N+]([O-])=O)=C2C(=O)N1C1CCC(=O)NC1=O KHEXQYOPAOPUQQ-UHFFFAOYSA-N 0.000 claims description 10
- OAKJQQAXSVQMHS-UHFFFAOYSA-N Hydrazine Chemical compound NN OAKJQQAXSVQMHS-UHFFFAOYSA-N 0.000 claims description 10
- NBIIXXVUZAFLBC-UHFFFAOYSA-N Phosphoric acid Chemical compound OP(O)(O)=O NBIIXXVUZAFLBC-UHFFFAOYSA-N 0.000 claims description 10
- 230000003301 hydrolyzing effect Effects 0.000 claims description 10
- 125000000882 C2-C6 alkenyl group Chemical group 0.000 claims description 9
- 125000003601 C2-C6 alkynyl group Chemical group 0.000 claims description 9
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical group Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 claims description 9
- 150000004945 aromatic hydrocarbons Chemical class 0.000 claims description 9
- RAABOESOVLLHRU-UHFFFAOYSA-N diazene Chemical compound N=N RAABOESOVLLHRU-UHFFFAOYSA-N 0.000 claims description 9
- 229910000071 diazene Inorganic materials 0.000 claims description 9
- 229910052763 palladium Inorganic materials 0.000 claims description 9
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 9
- 125000006376 (C3-C10) cycloalkyl group Chemical group 0.000 claims description 8
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical group [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 claims description 8
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 8
- 150000001925 cycloalkenes Chemical class 0.000 claims description 7
- CIWBSHSKHKDKBQ-JLAZNSOCSA-N Ascorbic acid Chemical compound OC[C@H](O)[C@H]1OC(=O)C(O)=C1O CIWBSHSKHKDKBQ-JLAZNSOCSA-N 0.000 claims description 6
- 125000005915 C6-C14 aryl group Chemical group 0.000 claims description 6
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 claims description 6
- VZTDIZULWFCMLS-UHFFFAOYSA-N ammonium formate Chemical compound [NH4+].[O-]C=O VZTDIZULWFCMLS-UHFFFAOYSA-N 0.000 claims description 6
- MGNZXYYWBUKAII-UHFFFAOYSA-N cyclohexa-1,3-diene Chemical compound C1CC=CC=C1 MGNZXYYWBUKAII-UHFFFAOYSA-N 0.000 claims description 6
- JVTAAEKCZFNVCJ-UHFFFAOYSA-N lactic acid Chemical compound CC(O)C(O)=O JVTAAEKCZFNVCJ-UHFFFAOYSA-N 0.000 claims description 6
- WFIZEGIEIOHZCP-UHFFFAOYSA-M potassium formate Chemical compound [K+].[O-]C=O WFIZEGIEIOHZCP-UHFFFAOYSA-M 0.000 claims description 6
- 125000004169 (C1-C6) alkyl group Chemical group 0.000 claims description 5
- YCPULGHBTPQLRH-UHFFFAOYSA-N 3-aminopiperidine-2,6-dione;hydron;chloride Chemical group Cl.NC1CCC(=O)NC1=O YCPULGHBTPQLRH-UHFFFAOYSA-N 0.000 claims description 5
- AVXURJPOCDRRFD-UHFFFAOYSA-N Hydroxylamine Chemical compound ON AVXURJPOCDRRFD-UHFFFAOYSA-N 0.000 claims description 5
- 229910000147 aluminium phosphate Inorganic materials 0.000 claims description 5
- 230000007062 hydrolysis Effects 0.000 claims description 5
- 238000006460 hydrolysis reaction Methods 0.000 claims description 5
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 5
- LMDZBCPBFSXMTL-UHFFFAOYSA-N 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide Chemical compound CCN=C=NCCCN(C)C LMDZBCPBFSXMTL-UHFFFAOYSA-N 0.000 claims description 4
- WETWJCDKMRHUPV-UHFFFAOYSA-N acetyl chloride Chemical compound CC(Cl)=O WETWJCDKMRHUPV-UHFFFAOYSA-N 0.000 claims description 4
- 239000012346 acetyl chloride Substances 0.000 claims description 4
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 4
- 125000005843 halogen group Chemical group 0.000 claims description 4
- 229910052739 hydrogen Inorganic materials 0.000 claims description 4
- 239000001257 hydrogen Substances 0.000 claims description 4
- 239000011981 lindlar catalyst Substances 0.000 claims description 4
- 229910003445 palladium oxide Inorganic materials 0.000 claims description 4
- JQPTYAILLJKUCY-UHFFFAOYSA-N palladium(ii) oxide Chemical compound [O-2].[Pd+2] JQPTYAILLJKUCY-UHFFFAOYSA-N 0.000 claims description 4
- 229910000030 sodium bicarbonate Inorganic materials 0.000 claims description 4
- 235000017557 sodium bicarbonate Nutrition 0.000 claims description 4
- NOOLISFMXDJSKH-UTLUCORTSA-N (+)-Neomenthol Chemical compound CC(C)[C@@H]1CC[C@@H](C)C[C@@H]1O NOOLISFMXDJSKH-UTLUCORTSA-N 0.000 claims description 3
- QBYIENPQHBMVBV-HFEGYEGKSA-N (2R)-2-hydroxy-2-phenylacetic acid Chemical compound O[C@@H](C(O)=O)c1ccccc1.O[C@@H](C(O)=O)c1ccccc1 QBYIENPQHBMVBV-HFEGYEGKSA-N 0.000 claims description 3
- NOOLISFMXDJSKH-UHFFFAOYSA-N DL-menthol Natural products CC(C)C1CCC(C)CC1O NOOLISFMXDJSKH-UHFFFAOYSA-N 0.000 claims description 3
- IWYDHOAUDWTVEP-UHFFFAOYSA-N R-2-phenyl-2-hydroxyacetic acid Natural products OC(=O)C(O)C1=CC=CC=C1 IWYDHOAUDWTVEP-UHFFFAOYSA-N 0.000 claims description 3
- VMHLLURERBWHNL-UHFFFAOYSA-M Sodium acetate Chemical compound [Na+].CC([O-])=O VMHLLURERBWHNL-UHFFFAOYSA-M 0.000 claims description 3
- 235000010323 ascorbic acid Nutrition 0.000 claims description 3
- 239000011668 ascorbic acid Substances 0.000 claims description 3
- 229960005070 ascorbic acid Drugs 0.000 claims description 3
- 150000001734 carboxylic acid salts Chemical class 0.000 claims description 3
- HPXRVTGHNJAIIH-UHFFFAOYSA-N cyclohexanol Chemical compound OC1CCCCC1 HPXRVTGHNJAIIH-UHFFFAOYSA-N 0.000 claims description 3
- XCIXKGXIYUWCLL-UHFFFAOYSA-N cyclopentanol Chemical compound OC1CCCC1 XCIXKGXIYUWCLL-UHFFFAOYSA-N 0.000 claims description 3
- 239000004310 lactic acid Substances 0.000 claims description 3
- 235000014655 lactic acid Nutrition 0.000 claims description 3
- 229960000448 lactic acid Drugs 0.000 claims description 3
- 229960002510 mandelic acid Drugs 0.000 claims description 3
- 229940041616 menthol Drugs 0.000 claims description 3
- 125000004043 oxo group Chemical group O=* 0.000 claims description 3
- WVDDGKGOMKODPV-ZQBYOMGUSA-N phenyl(114C)methanol Chemical compound O[14CH2]C1=CC=CC=C1 WVDDGKGOMKODPV-ZQBYOMGUSA-N 0.000 claims description 3
- 239000010970 precious metal Substances 0.000 claims description 3
- 239000001632 sodium acetate Substances 0.000 claims description 3
- 235000017281 sodium acetate Nutrition 0.000 claims description 3
- 229910000029 sodium carbonate Inorganic materials 0.000 claims description 3
- NLJMYIDDQXHKNR-UHFFFAOYSA-K sodium citrate Chemical compound O.O.[Na+].[Na+].[Na+].[O-]C(=O)CC(O)(CC([O-])=O)C([O-])=O NLJMYIDDQXHKNR-UHFFFAOYSA-K 0.000 claims description 3
- 150000003505 terpenes Chemical class 0.000 claims description 3
- 235000007586 terpenes Nutrition 0.000 claims description 3
- JKTCBAGSMQIFNL-UHFFFAOYSA-N 2,3-dihydrofuran Chemical compound C1CC=CO1 JKTCBAGSMQIFNL-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- ISSLESFGPVAXKC-UHFFFAOYSA-N n-[3-(2,6-dioxopiperidin-3-yl)-2-methyl-4-oxoquinazolin-5-yl]formamide Chemical compound CC1=NC2=CC=CC(NC=O)=C2C(=O)N1C1CCC(=O)NC1=O ISSLESFGPVAXKC-UHFFFAOYSA-N 0.000 claims 5
- BVJRNKXVSYLNFD-UHFFFAOYSA-N 3-(5-amino-2-methyl-4-oxoquinazolin-3-yl)piperidine-2,6-dione;hydrochloride Chemical compound Cl.CC1=NC2=CC=CC(N)=C2C(=O)N1C1CCC(=O)NC1=O BVJRNKXVSYLNFD-UHFFFAOYSA-N 0.000 claims 4
- XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 claims 4
- 229910021205 NaH2PO2 Inorganic materials 0.000 claims 3
- 229910019213 POCl3 Inorganic materials 0.000 claims 2
- 239000003377 acid catalyst Substances 0.000 claims 2
- UHZYTMXLRWXGPK-UHFFFAOYSA-N phosphorus pentachloride Chemical compound ClP(Cl)(Cl)(Cl)Cl UHZYTMXLRWXGPK-UHFFFAOYSA-N 0.000 claims 1
- FAIAAWCVCHQXDN-UHFFFAOYSA-N phosphorus trichloride Chemical compound ClP(Cl)Cl FAIAAWCVCHQXDN-UHFFFAOYSA-N 0.000 claims 1
- 238000002360 preparation method Methods 0.000 abstract description 19
- 230000008569 process Effects 0.000 abstract description 6
- KNCYXPMJDCCGSJ-UHFFFAOYSA-N piperidine-2,6-dione Chemical compound O=C1CCCC(=O)N1 KNCYXPMJDCCGSJ-UHFFFAOYSA-N 0.000 description 115
- ZHNUHDYFZUAESO-UHFFFAOYSA-N Formamide Chemical compound NC=O ZHNUHDYFZUAESO-UHFFFAOYSA-N 0.000 description 62
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 51
- ZWEHNKRNPOVVGH-UHFFFAOYSA-N 2-Butanone Chemical compound CCC(C)=O ZWEHNKRNPOVVGH-UHFFFAOYSA-N 0.000 description 32
- 125000003118 aryl group Chemical group 0.000 description 30
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 28
- 150000001875 compounds Chemical class 0.000 description 26
- IVKNUIVDQMARCO-UHFFFAOYSA-N oxazin-4-one Chemical compound O=C1C=CON=C1 IVKNUIVDQMARCO-UHFFFAOYSA-N 0.000 description 25
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 24
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 24
- 239000004215 Carbon black (E152) Substances 0.000 description 23
- 229930195733 hydrocarbon Natural products 0.000 description 23
- BASFCYQUMIYNBI-UHFFFAOYSA-N platinum Chemical compound [Pt] BASFCYQUMIYNBI-UHFFFAOYSA-N 0.000 description 23
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 21
- 125000004432 carbon atom Chemical group C* 0.000 description 21
- 238000006344 deformylation reaction Methods 0.000 description 21
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 20
- 230000006198 deformylation Effects 0.000 description 20
- 125000000217 alkyl group Chemical group 0.000 description 19
- IAZDPXIOMUYVGZ-UHFFFAOYSA-N Dimethylsulphoxide Chemical compound CS(C)=O IAZDPXIOMUYVGZ-UHFFFAOYSA-N 0.000 description 16
- 125000000753 cycloalkyl group Chemical group 0.000 description 14
- 150000002825 nitriles Chemical class 0.000 description 14
- 239000011541 reaction mixture Substances 0.000 description 14
- 125000003342 alkenyl group Chemical group 0.000 description 13
- 238000006722 reduction reaction Methods 0.000 description 13
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 description 12
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 12
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 12
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 12
- 125000000304 alkynyl group Chemical group 0.000 description 12
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 12
- 230000009467 reduction Effects 0.000 description 12
- 150000001412 amines Chemical class 0.000 description 11
- 229920006395 saturated elastomer Polymers 0.000 description 10
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 10
- RGSFGYAAUTVSQA-UHFFFAOYSA-N Cyclopentane Chemical compound C1CCCC1 RGSFGYAAUTVSQA-UHFFFAOYSA-N 0.000 description 9
- XBDQKXXYIPTUBI-UHFFFAOYSA-M Propionate Chemical compound CCC([O-])=O XBDQKXXYIPTUBI-UHFFFAOYSA-M 0.000 description 9
- DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 9
- 229940125898 compound 5 Drugs 0.000 description 9
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 9
- SYBYTAAJFKOIEJ-UHFFFAOYSA-N 3-Methylbutan-2-one Chemical compound CC(C)C(C)=O SYBYTAAJFKOIEJ-UHFFFAOYSA-N 0.000 description 8
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 8
- XTHFKEDIFFGKHM-UHFFFAOYSA-N Dimethoxyethane Chemical compound COCCOC XTHFKEDIFFGKHM-UHFFFAOYSA-N 0.000 description 8
- NTIZESTWPVYFNL-UHFFFAOYSA-N Methyl isobutyl ketone Chemical compound CC(C)CC(C)=O NTIZESTWPVYFNL-UHFFFAOYSA-N 0.000 description 8
- UIHCLUNTQKBZGK-UHFFFAOYSA-N Methyl isobutyl ketone Natural products CCC(C)C(C)=O UIHCLUNTQKBZGK-UHFFFAOYSA-N 0.000 description 8
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 8
- AMQJEAYHLZJPGS-UHFFFAOYSA-N N-Pentanol Chemical compound CCCCCO AMQJEAYHLZJPGS-UHFFFAOYSA-N 0.000 description 8
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 8
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
- RDOXTESZEPMUJZ-UHFFFAOYSA-N anisole Chemical compound COC1=CC=CC=C1 RDOXTESZEPMUJZ-UHFFFAOYSA-N 0.000 description 8
- DXHPZXWIPWDXHJ-UHFFFAOYSA-N carbon monosulfide Chemical compound [S+]#[C-] DXHPZXWIPWDXHJ-UHFFFAOYSA-N 0.000 description 8
- MVPPADPHJFYWMZ-UHFFFAOYSA-N chlorobenzene Chemical compound ClC1=CC=CC=C1 MVPPADPHJFYWMZ-UHFFFAOYSA-N 0.000 description 8
- RWGFKTVRMDUZSP-UHFFFAOYSA-N cumene Chemical compound CC(C)C1=CC=CC=C1 RWGFKTVRMDUZSP-UHFFFAOYSA-N 0.000 description 8
- USIUVYZYUHIAEV-UHFFFAOYSA-N diphenyl ether Chemical compound C=1C=CC=CC=1OC1=CC=CC=C1 USIUVYZYUHIAEV-UHFFFAOYSA-N 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- UAEPNZWRGJTJPN-UHFFFAOYSA-N methylcyclohexane Chemical compound CC1CCCCC1 UAEPNZWRGJTJPN-UHFFFAOYSA-N 0.000 description 8
- LQNUZADURLCDLV-UHFFFAOYSA-N nitrobenzene Chemical compound [O-][N+](=O)C1=CC=CC=C1 LQNUZADURLCDLV-UHFFFAOYSA-N 0.000 description 8
- 125000006413 ring segment Chemical group 0.000 description 8
- VZGDMQKNWNREIO-UHFFFAOYSA-N tetrachloromethane Chemical compound ClC(Cl)(Cl)Cl VZGDMQKNWNREIO-UHFFFAOYSA-N 0.000 description 8
- 150000001336 alkenes Chemical class 0.000 description 7
- 125000002619 bicyclic group Chemical group 0.000 description 7
- 125000005842 heteroatom Chemical group 0.000 description 7
- 239000002815 homogeneous catalyst Substances 0.000 description 7
- 150000002430 hydrocarbons Chemical class 0.000 description 7
- JMMWKPVZQRWMSS-UHFFFAOYSA-N isopropanol acetate Natural products CC(C)OC(C)=O JMMWKPVZQRWMSS-UHFFFAOYSA-N 0.000 description 7
- 229940011051 isopropyl acetate Drugs 0.000 description 7
- GWYFCOCPABKNJV-UHFFFAOYSA-M isovalerate Chemical compound CC(C)CC([O-])=O GWYFCOCPABKNJV-UHFFFAOYSA-M 0.000 description 7
- 229910052697 platinum Inorganic materials 0.000 description 7
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D401/00—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom
- C07D401/02—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings
- C07D401/04—Heterocyclic compounds containing two or more hetero rings, having nitrogen atoms as the only ring hetero atoms, at least one ring being a six-membered ring with only one nitrogen atom containing two hetero rings directly linked by a ring-member-to-ring-member bond
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Plural Heterocyclic Compounds (AREA)
- Health & Medical Sciences (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Veterinary Medicine (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201361818254P | 2013-05-01 | 2013-05-01 | |
| US61/818,254 | 2013-05-01 | ||
| PCT/US2014/036083 WO2014179416A1 (en) | 2013-05-01 | 2014-04-30 | Synthesis of 3-(5-amino-2-methyl-4-oxoquinazolin-3(4h)-yl) piperidine-2,6-dione |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2910971A1 true CA2910971A1 (en) | 2014-11-06 |
Family
ID=50885008
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2910971A Abandoned CA2910971A1 (en) | 2013-05-01 | 2014-04-30 | Synthesis of 3-(5-amino-2-methyl-4-oxoquinazolin-3(4h)-yl)piperidine-2,6-dione |
Country Status (26)
| Country | Link |
|---|---|
| US (3) | US9067912B2 (https=) |
| EP (2) | EP3199532A1 (https=) |
| JP (2) | JP6490055B2 (https=) |
| KR (1) | KR20160003228A (https=) |
| CN (2) | CN107935994A (https=) |
| AR (1) | AR096165A1 (https=) |
| AU (2) | AU2014260011A1 (https=) |
| CA (1) | CA2910971A1 (https=) |
| CY (1) | CY1119525T1 (https=) |
| DK (1) | DK2991976T3 (https=) |
| ES (1) | ES2645944T3 (https=) |
| HR (1) | HRP20171535T1 (https=) |
| HU (1) | HUE034770T2 (https=) |
| LT (1) | LT2991976T (https=) |
| MX (1) | MX363652B (https=) |
| NZ (1) | NZ628322A (https=) |
| PH (1) | PH12015502477A1 (https=) |
| PL (1) | PL2991976T3 (https=) |
| PT (1) | PT2991976T (https=) |
| RS (1) | RS56565B1 (https=) |
| RU (1) | RU2015151359A (https=) |
| SG (1) | SG11201508836XA (https=) |
| SI (1) | SI2991976T1 (https=) |
| SM (1) | SMT201700513T1 (https=) |
| TW (1) | TW201536766A (https=) |
| WO (1) | WO2014179416A1 (https=) |
Families Citing this family (8)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| DK2428513T3 (en) | 2006-09-26 | 2017-08-21 | Celgene Corp | 5-substituted quinazolinone derivatives as anti-cancer agents |
| JP5959543B2 (ja) | 2011-03-11 | 2016-08-02 | セルジーン コーポレイション | ３−（５−アミノ−２−メチル−４−オキソ−４ｈ−キナゾリン−３−イル）−ピペリジン−２，６−ジオンの固体形態、並びにそれらの医薬組成物及び使用 |
| ES2814952T3 (es) | 2012-09-04 | 2021-03-29 | Celgene Corp | Isotopólogos de 3-(5-amino-2-metil-4-oxoquinazolin-3(4H)-il) piperidina-2-6-diona y métodos de preparación de los mismos |
| EP3316888A1 (en) | 2015-07-02 | 2018-05-09 | Celgene Corporation | Combination therapy for treatment of hematological cancers and solid tumors |
| CN106083622B (zh) * | 2016-06-16 | 2018-06-19 | 常州齐晖药业有限公司 | 一种甲苯咪唑中间体3,4-二氨基二苯甲酮的制备方法 |
| WO2018165142A1 (en) * | 2017-03-07 | 2018-09-13 | Celgene Corporation | Solid forms of 3-(5-amino-2-methyl-4-oxo-4h-quinazolin-3-yl)-piperidine-2,6-dione, and their pharmaceutical compositions and uses |
| CN113101295A (zh) * | 2020-03-20 | 2021-07-13 | 上海疆云医疗健康科技有限公司 | 二苯乙烯类似物在治疗糖尿病肾脏疾病中的用途 |
| KR20240055046A (ko) * | 2021-09-02 | 2024-04-26 | 신톤 비.브이. | 오시머티닙을 제조하는 방법 |
Family Cites Families (6)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| JP2009539878A (ja) * | 2006-06-08 | 2009-11-19 | アレイ バイオファーマ、インコーポレイテッド | キノリン化合物および使用方法 |
| DK2428513T3 (en) * | 2006-09-26 | 2017-08-21 | Celgene Corp | 5-substituted quinazolinone derivatives as anti-cancer agents |
| JP5959543B2 (ja) * | 2011-03-11 | 2016-08-02 | セルジーン コーポレイション | ３−（５−アミノ−２−メチル−４−オキソ−４ｈ−キナゾリン−３−イル）−ピペリジン−２，６−ジオンの固体形態、並びにそれらの医薬組成物及び使用 |
| AU2012229300B2 (en) * | 2011-03-11 | 2017-04-20 | Celgene Corporation | Methods of treating cancer using 3-(5-amino-2-methyl-4-oxo-4H-quinazolin-3-yl)-piperidine-2,6-dione |
| ES2814952T3 (es) * | 2012-09-04 | 2021-03-29 | Celgene Corp | Isotopólogos de 3-(5-amino-2-metil-4-oxoquinazolin-3(4H)-il) piperidina-2-6-diona y métodos de preparación de los mismos |
| CA2935495C (en) * | 2013-01-14 | 2021-04-20 | Deuterx, Llc | 3-(5-substituted-4-oxoquinazolin-3(4h)-yl)-3-deutero-piperidine-2,6-dione derivatives |
-
2014
- 2014-04-30 SM SM20170513T patent/SMT201700513T1/it unknown
- 2014-04-30 HR HRP20171535TT patent/HRP20171535T1/hr unknown
- 2014-04-30 AR ARP140101806A patent/AR096165A1/es unknown
- 2014-04-30 LT LTEP14728381.6T patent/LT2991976T/lt unknown
- 2014-04-30 AU AU2014260011A patent/AU2014260011A1/en not_active Abandoned
- 2014-04-30 HU HUE14728381A patent/HUE034770T2/hu unknown
- 2014-04-30 EP EP17161076.9A patent/EP3199532A1/en not_active Withdrawn
- 2014-04-30 CA CA2910971A patent/CA2910971A1/en not_active Abandoned
- 2014-04-30 CN CN201810004591.8A patent/CN107935994A/zh active Pending
- 2014-04-30 WO PCT/US2014/036083 patent/WO2014179416A1/en not_active Ceased
- 2014-04-30 ES ES14728381.6T patent/ES2645944T3/es active Active
- 2014-04-30 KR KR1020157034184A patent/KR20160003228A/ko not_active Withdrawn
- 2014-04-30 TW TW103115643A patent/TW201536766A/zh unknown
- 2014-04-30 CN CN201480038438.7A patent/CN105377831B/zh not_active Expired - Fee Related
- 2014-04-30 EP EP14728381.6A patent/EP2991976B1/en active Active
- 2014-04-30 SI SI201430431T patent/SI2991976T1/sl unknown
- 2014-04-30 PT PT147283816T patent/PT2991976T/pt unknown
- 2014-04-30 DK DK14728381.6T patent/DK2991976T3/da active
- 2014-04-30 SG SG11201508836XA patent/SG11201508836XA/en unknown
- 2014-04-30 US US14/266,448 patent/US9067912B2/en not_active Expired - Fee Related
- 2014-04-30 NZ NZ628322A patent/NZ628322A/en not_active IP Right Cessation
- 2014-04-30 RU RU2015151359A patent/RU2015151359A/ru unknown
- 2014-04-30 MX MX2015015073A patent/MX363652B/es unknown
- 2014-04-30 JP JP2016511825A patent/JP6490055B2/ja not_active Expired - Fee Related
- 2014-04-30 PL PL14728381T patent/PL2991976T3/pl unknown
- 2014-04-30 RS RS20171105A patent/RS56565B1/sr unknown
-
2015
- 2015-06-10 US US14/736,146 patent/US9266858B2/en not_active Expired - Fee Related
- 2015-09-24 US US14/864,614 patent/US9303014B2/en not_active Expired - Fee Related
- 2015-10-27 PH PH12015502477A patent/PH12015502477A1/en unknown
-
2017
- 2017-02-13 AU AU2017200965A patent/AU2017200965A1/en not_active Abandoned
- 2017-10-26 CY CY20171101119T patent/CY1119525T1/el unknown
-
2018
- 2018-12-06 JP JP2018229189A patent/JP2019069958A/ja active Pending
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