CN108055843A - 苯并二氮杂*衍生物的合成 - Google Patents
苯并二氮杂*衍生物的合成 Download PDFInfo
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- CN108055843A CN108055843A CN201680045936.3A CN201680045936A CN108055843A CN 108055843 A CN108055843 A CN 108055843A CN 201680045936 A CN201680045936 A CN 201680045936A CN 108055843 A CN108055843 A CN 108055843A
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- 229940049706 benzodiazepine Drugs 0.000 title abstract description 10
- 230000015572 biosynthetic process Effects 0.000 title abstract description 10
- 238000003786 synthesis reaction Methods 0.000 title abstract description 10
- SVUOLADPCWQTTE-UHFFFAOYSA-N 1h-1,2-benzodiazepine Chemical compound N1N=CC=CC2=CC=CC=C12 SVUOLADPCWQTTE-UHFFFAOYSA-N 0.000 title description 7
- 238000000034 method Methods 0.000 claims abstract description 72
- 150000001875 compounds Chemical class 0.000 claims description 210
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical group ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 claims description 115
- 239000000203 mixture Substances 0.000 claims description 83
- -1 nitro, carboxyl Chemical group 0.000 claims description 40
- 150000003839 salts Chemical class 0.000 claims description 39
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 claims description 36
- 239000011541 reaction mixture Substances 0.000 claims description 36
- 125000001424 substituent group Chemical group 0.000 claims description 34
- 230000000903 blocking effect Effects 0.000 claims description 31
- 125000001931 aliphatic group Chemical group 0.000 claims description 30
- 230000003287 optical effect Effects 0.000 claims description 29
- 125000001072 heteroaryl group Chemical group 0.000 claims description 25
- YGYAWVDWMABLBF-UHFFFAOYSA-N Phosgene Chemical compound ClC(Cl)=O YGYAWVDWMABLBF-UHFFFAOYSA-N 0.000 claims description 21
- 239000000010 aprotic solvent Substances 0.000 claims description 21
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 21
- 229910052799 carbon Inorganic materials 0.000 claims description 18
- 229910052739 hydrogen Inorganic materials 0.000 claims description 18
- 239000002904 solvent Substances 0.000 claims description 18
- 150000002367 halogens Chemical class 0.000 claims description 17
- 229910052736 halogen Inorganic materials 0.000 claims description 16
- 238000006243 chemical reaction Methods 0.000 claims description 14
- 239000001257 hydrogen Substances 0.000 claims description 14
- 125000000217 alkyl group Chemical group 0.000 claims description 13
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 13
- 230000004224 protection Effects 0.000 claims description 12
- 238000006467 substitution reaction Methods 0.000 claims description 12
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 11
- 125000005842 heteroatom Chemical group 0.000 claims description 10
- 150000001721 carbon Chemical group 0.000 claims description 9
- 125000000623 heterocyclic group Chemical group 0.000 claims description 9
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 8
- 238000010511 deprotection reaction Methods 0.000 claims description 8
- 150000002148 esters Chemical class 0.000 claims description 8
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 8
- 230000008859 change Effects 0.000 claims description 7
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 7
- 239000000126 substance Substances 0.000 claims description 7
- 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- FZFAMSAMCHXGEF-UHFFFAOYSA-N chloro formate Chemical compound ClOC=O FZFAMSAMCHXGEF-UHFFFAOYSA-N 0.000 claims description 6
- 125000000339 4-pyridyl group Chemical group N1=C([H])C([H])=C([*])C([H])=C1[H] 0.000 claims description 5
- 229910052794 bromium Inorganic materials 0.000 claims description 5
- 229910052801 chlorine Inorganic materials 0.000 claims description 5
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 5
- 239000003814 drug Substances 0.000 claims description 5
- UCPYLLCMEDAXFR-UHFFFAOYSA-N triphosgene Chemical compound ClC(Cl)(Cl)OC(=O)OC(Cl)(Cl)Cl UCPYLLCMEDAXFR-UHFFFAOYSA-N 0.000 claims description 5
- 125000004105 2-pyridyl group Chemical group N1=C([*])C([H])=C([H])C([H])=C1[H] 0.000 claims description 4
- 125000003349 3-pyridyl group Chemical group N1=C([H])C([*])=C([H])C([H])=C1[H] 0.000 claims description 4
- ZJIFDEVVTPEXDL-UHFFFAOYSA-N (2,5-dioxopyrrolidin-1-yl) hydrogen carbonate Chemical class OC(=O)ON1C(=O)CCC1=O ZJIFDEVVTPEXDL-UHFFFAOYSA-N 0.000 claims description 3
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 3
- 229910052731 fluorine Inorganic materials 0.000 claims description 3
- 239000007789 gas Substances 0.000 claims description 3
- 125000004076 pyridyl group Chemical group 0.000 claims description 3
- KZNICNPSHKQLFF-UHFFFAOYSA-N succinimide Chemical class O=C1CCC(=O)N1 KZNICNPSHKQLFF-UHFFFAOYSA-N 0.000 claims description 3
- 229910006069 SO3H Inorganic materials 0.000 claims description 2
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 claims description 2
- 125000006222 dimethylaminomethyl group Chemical group [H]C([H])([H])N(C([H])([H])[H])C([H])([H])* 0.000 claims description 2
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 claims description 2
- 150000002825 nitriles Chemical class 0.000 claims description 2
- 125000002730 succinyl group Chemical group C(CCC(=O)*)(=O)* 0.000 claims description 2
- 150000001557 benzodiazepines Chemical class 0.000 abstract 1
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 74
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 69
- 239000000243 solution Substances 0.000 description 62
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 54
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 48
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 42
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 40
- 238000003756 stirring Methods 0.000 description 35
- 239000007787 solid Substances 0.000 description 34
- 239000002585 base Substances 0.000 description 32
- RTZKZFJDLAIYFH-UHFFFAOYSA-N ether Substances CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 25
- 238000004809 thin layer chromatography Methods 0.000 description 25
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 24
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 23
- 239000000047 product Substances 0.000 description 21
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 20
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 18
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 17
- 238000004128 high performance liquid chromatography Methods 0.000 description 17
- 239000010410 layer Substances 0.000 description 17
- 125000003118 aryl group Chemical group 0.000 description 16
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 15
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 15
- 238000005160 1H NMR spectroscopy Methods 0.000 description 13
- 0 CCC[C@](*)(C[U]=C)C1=CC2=CCCC(C(c3ncccc3)=N)=C2C=C(CC(C)=O)C1 Chemical compound CCC[C@](*)(C[U]=C)C1=CC2=CCCC(C(c3ncccc3)=N)=C2C=C(CC(C)=O)C1 0.000 description 13
- QGZKDVFQNNGYKY-UHFFFAOYSA-N ammonia Natural products N QGZKDVFQNNGYKY-UHFFFAOYSA-N 0.000 description 13
- 230000000694 effects Effects 0.000 description 13
- 239000003480 eluent Substances 0.000 description 13
- 239000003921 oil Substances 0.000 description 13
- UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 12
- 239000004519 grease Substances 0.000 description 12
- 239000007788 liquid Substances 0.000 description 12
- 108020003175 receptors Proteins 0.000 description 12
- 102000005962 receptors Human genes 0.000 description 12
- 239000002002 slurry Substances 0.000 description 11
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 10
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 10
- 239000003513 alkali Substances 0.000 description 10
- 239000013078 crystal Substances 0.000 description 10
- 238000001914 filtration Methods 0.000 description 10
- 230000002829 reductive effect Effects 0.000 description 10
- JGFZNNIVVJXRND-UHFFFAOYSA-N N,N-Diisopropylethylamine (DIPEA) Chemical compound CCN(C(C)C)C(C)C JGFZNNIVVJXRND-UHFFFAOYSA-N 0.000 description 9
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 9
- 102400000921 Gastrin Human genes 0.000 description 8
- YNAVUWVOSKDBBP-UHFFFAOYSA-N Morpholine Chemical compound C1COCCN1 YNAVUWVOSKDBBP-UHFFFAOYSA-N 0.000 description 8
- 239000002253 acid Substances 0.000 description 8
- 239000008186 active pharmaceutical agent Substances 0.000 description 8
- 239000003153 chemical reaction reagent Substances 0.000 description 8
- 201000010099 disease Diseases 0.000 description 8
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 8
- 238000004519 manufacturing process Methods 0.000 description 8
- 239000012299 nitrogen atmosphere Substances 0.000 description 8
- 230000036470 plasma concentration Effects 0.000 description 8
- 210000002784 stomach Anatomy 0.000 description 8
- 108010079943 Pentagastrin Proteins 0.000 description 7
- 229910021529 ammonia Inorganic materials 0.000 description 7
- 239000003795 chemical substances by application Substances 0.000 description 7
- 238000004296 chiral HPLC Methods 0.000 description 7
- 239000000284 extract Substances 0.000 description 7
- 238000010438 heat treatment Methods 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- ALXRNCVIQSDJAO-KRCBVYEFSA-N pentagastrin Chemical compound C([C@H](NC(=O)[C@H](CC(O)=O)NC(=O)[C@@H](NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)CCNC(=O)OCC(C)C)CCSC)C(N)=O)C1=CC=CC=C1 ALXRNCVIQSDJAO-KRCBVYEFSA-N 0.000 description 7
- 229960000444 pentagastrin Drugs 0.000 description 7
- 239000002994 raw material Substances 0.000 description 7
- 238000011160 research Methods 0.000 description 7
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- 238000010792 warming Methods 0.000 description 7
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 6
- 241000282414 Homo sapiens Species 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical compound [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 6
- 125000001118 alkylidene group Chemical group 0.000 description 6
- 210000004027 cell Anatomy 0.000 description 6
- 230000036541 health Effects 0.000 description 6
- IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 6
- 229910000041 hydrogen chloride Inorganic materials 0.000 description 6
- 125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 6
- 229910052757 nitrogen Inorganic materials 0.000 description 6
- 229910052760 oxygen Inorganic materials 0.000 description 6
- LPNYRYFBWFDTMA-UHFFFAOYSA-N potassium tert-butoxide Chemical compound [K+].CC(C)(C)[O-] LPNYRYFBWFDTMA-UHFFFAOYSA-N 0.000 description 6
- 230000008569 process Effects 0.000 description 6
- 238000010992 reflux Methods 0.000 description 6
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 5
- 108010052343 Gastrins Proteins 0.000 description 5
- TZRXHJWUDPFEEY-UHFFFAOYSA-N Pentaerythritol Tetranitrate Chemical compound [O-][N+](=O)OCC(CO[N+]([O-])=O)(CO[N+]([O-])=O)CO[N+]([O-])=O TZRXHJWUDPFEEY-UHFFFAOYSA-N 0.000 description 5
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 5
- 239000005557 antagonist Substances 0.000 description 5
- 239000007864 aqueous solution Substances 0.000 description 5
- 125000004429 atom Chemical group 0.000 description 5
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 5
- 229910002092 carbon dioxide Inorganic materials 0.000 description 5
- AOXOCDRNSPFDPE-UKEONUMOSA-N chembl413654 Chemical compound C([C@H](C(=O)NCC(=O)N[C@H](CC=1C2=CC=CC=C2NC=1)C(=O)N[C@H](CCSC)C(=O)N[C@H](CC(O)=O)C(=O)N[C@H](CC=1C=CC=CC=1)C(N)=O)NC(=O)[C@@H](C)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CCC(O)=O)NC(=O)[C@H](CC(C)C)NC(=O)[C@H](CC=1C2=CC=CC=C2NC=1)NC(=O)[C@H]1N(CCC1)C(=O)CNC(=O)[C@@H](N)CCC(O)=O)C1=CC=C(O)C=C1 AOXOCDRNSPFDPE-UKEONUMOSA-N 0.000 description 5
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- HPALAKNZSZLMCH-UHFFFAOYSA-M sodium;chloride;hydrate Chemical class O.[Na+].[Cl-] HPALAKNZSZLMCH-UHFFFAOYSA-M 0.000 description 5
- 238000012360 testing method Methods 0.000 description 5
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- 150000005762 2-bromopyridine Chemical class 0.000 description 4
- VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 4
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- 235000011114 ammonium hydroxide Nutrition 0.000 description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 description 4
- 239000012964 benzotriazole Substances 0.000 description 4
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- 229940125773 compound 10 Drugs 0.000 description 4
- 239000012043 crude product Substances 0.000 description 4
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- GTCAXTIRRLKXRU-UHFFFAOYSA-N methyl carbamate Chemical compound COC(N)=O GTCAXTIRRLKXRU-UHFFFAOYSA-N 0.000 description 4
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- 238000002360 preparation method Methods 0.000 description 4
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- DYHSDKLCOJIUFX-UHFFFAOYSA-N tert-butoxycarbonyl anhydride Chemical compound CC(C)(C)OC(=O)OC(=O)OC(C)(C)C DYHSDKLCOJIUFX-UHFFFAOYSA-N 0.000 description 4
- 238000001291 vacuum drying Methods 0.000 description 4
- 125000003088 (fluoren-9-ylmethoxy)carbonyl group Chemical group 0.000 description 3
- SYBYTAAJFKOIEJ-UHFFFAOYSA-N 3-Methylbutan-2-one Chemical compound CC(C)C(C)=O SYBYTAAJFKOIEJ-UHFFFAOYSA-N 0.000 description 3
- XJCVRTZCHMZPBD-UHFFFAOYSA-N 3-nitroaniline Chemical class NC1=CC=CC([N+]([O-])=O)=C1 XJCVRTZCHMZPBD-UHFFFAOYSA-N 0.000 description 3
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- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
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- 125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 3
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- 125000003342 alkenyl group Chemical group 0.000 description 3
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- QRUDEWIWKLJBPS-UHFFFAOYSA-N benzotriazole Chemical compound C1=CC=C2N[N][N]C2=C1 QRUDEWIWKLJBPS-UHFFFAOYSA-N 0.000 description 3
- 125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 3
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- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 3
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- 125000001820 oxy group Chemical group [*:1]O[*:2] 0.000 description 3
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- JHLVEBNWCCKSGY-UHFFFAOYSA-N tert-butyl n-methylcarbamate Chemical compound CNC(=O)OC(C)(C)C JHLVEBNWCCKSGY-UHFFFAOYSA-N 0.000 description 3
- 239000002562 thickening agent Substances 0.000 description 3
- DTQVDTLACAAQTR-UHFFFAOYSA-N trifluoroacetic acid Substances OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 3
- ARLKVQYMFRECLV-JSGCOSHPSA-N (2s)-2-[[(2s)-2-amino-3-(1h-indol-3-yl)propanoyl]amino]-4-methylsulfanylbutanamide Chemical compound C1=CC=C2C(C[C@H](N)C(=O)N[C@@H](CCSC)C(N)=O)=CNC2=C1 ARLKVQYMFRECLV-JSGCOSHPSA-N 0.000 description 2
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- 125000001981 tert-butyldimethylsilyl group Chemical group [H]C([H])([H])[Si]([H])(C([H])([H])[H])[*]C(C([H])([H])[H])(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
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Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D243/00—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms
- C07D243/06—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4
- C07D243/10—Heterocyclic compounds containing seven-membered rings having two nitrogen atoms as the only ring hetero atoms having the nitrogen atoms in positions 1 and 4 condensed with carbocyclic rings or ring systems
- C07D243/14—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines
- C07D243/16—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals
- C07D243/18—1,4-Benzodiazepines; Hydrogenated 1,4-benzodiazepines substituted in position 5 by aryl radicals substituted in position 2 by nitrogen, oxygen or sulfur atoms
- C07D243/24—Oxygen atoms
- C07D243/26—Preparation from compounds already containing the benzodiazepine skeleton
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C259/00—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups
- C07C259/04—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids
- C07C259/10—Compounds containing carboxyl groups, an oxygen atom of a carboxyl group being replaced by a nitrogen atom, this nitrogen atom being further bound to an oxygen atom and not being part of nitro or nitroso groups without replacement of the other oxygen atom of the carboxyl group, e.g. hydroxamic acids having carbon atoms of hydroxamic groups bound to carbon atoms of six-membered aromatic rings
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07C—ACYCLIC OR CARBOCYCLIC COMPOUNDS
- C07C271/00—Derivatives of carbamic acids, i.e. compounds containing any of the groups, the nitrogen atom not being part of nitro or nitroso groups
- C07C271/06—Esters of carbamic acids
- C07C271/08—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms
- C07C271/26—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring
- C07C271/28—Esters of carbamic acids having oxygen atoms of carbamate groups bound to acyclic carbon atoms with the nitrogen atom of at least one of the carbamate groups bound to a carbon atom of a six-membered aromatic ring to a carbon atom of a non-condensed six-membered aromatic ring
-
- 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)
- Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| GBGB1513979.3A GB201513979D0 (en) | 2015-08-07 | 2015-08-07 | Synthesis of benzodiazepine derivatives |
| PCT/GB2015/052291 WO2016020698A1 (en) | 2014-08-08 | 2015-08-07 | Benzodiazepine derivatives as cck2/gastrin receptor antagonists |
| GBPCT/GB2015/052291 | 2015-08-07 | ||
| GB1513979.3 | 2015-08-07 | ||
| PCT/GB2016/052442 WO2017025727A1 (en) | 2015-08-07 | 2016-08-05 | Synthesis of benzodiazepine derivatives |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CN108055843A true CN108055843A (zh) | 2018-05-18 |
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| CN201680045936.3A Pending CN108055843A (zh) | 2015-08-07 | 2016-08-05 | 苯并二氮杂*衍生物的合成 |
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| US (3) | US10570102B2 (enExample) |
| EP (2) | EP3868746A1 (enExample) |
| JP (1) | JP6979398B2 (enExample) |
| CN (1) | CN108055843A (enExample) |
| GB (1) | GB201513979D0 (enExample) |
| WO (1) | WO2017025727A1 (enExample) |
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| CN107162923B (zh) * | 2017-06-12 | 2019-04-23 | 浙江新三和医药化工股份有限公司 | 一种邻氨基苯乙酮的制备方法 |
| EP3911649A1 (en) * | 2019-01-17 | 2021-11-24 | F. Hoffmann-La Roche AG | A process for the preparation of tetrahydropyridopyrimidines |
Citations (3)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| CN1074216A (zh) * | 1991-10-24 | 1993-07-14 | 格拉克索公司 | 尿素衍生物 |
| CN1075717A (zh) * | 1992-02-27 | 1993-09-01 | 山之内制药株式会社 | 苯骈二氮杂衍生物 |
| US5563136A (en) * | 1991-10-10 | 1996-10-08 | Rhone-Poulenc Rorer S.A. | 3-Ureidobenzodiazepinones useful as antagonists of CCK or of gastrin |
Family Cites Families (21)
| Publication number | Priority date | Publication date | Assignee | Title |
|---|---|---|---|---|
| US4138433A (en) * | 1975-06-26 | 1979-02-06 | Hoechst Aktiengesellschaft | Process for preparing 1,2-oxa-phospholanes |
| US4081455A (en) * | 1976-06-02 | 1978-03-28 | Pfizer Inc. | 6-Amino-2,2-dimethyl-3-cyanopenams |
| CA1332410C (en) * | 1984-06-26 | 1994-10-11 | Roger M. Freidinger | Benzodiazepine analogs |
| US4820834A (en) | 1984-06-26 | 1989-04-11 | Merck & Co., Inc. | Benzodiazepine analogs |
| CA2032226A1 (en) | 1989-12-18 | 1991-06-19 | Mark G. Bock | Benzodiazepine analogs |
| US4994258A (en) * | 1990-03-05 | 1991-02-19 | Merck & Co., Inc. | Gamma emitting, CCK-A antagonists for pancreatic imaging |
| CA2056809A1 (en) | 1990-12-07 | 1992-06-08 | Mark G. Bock | Benzodiazepine analogs |
| US5218114A (en) | 1991-04-10 | 1993-06-08 | Merck & Co., Inc. | Cholecystokinin antagonists |
| EP0538945A1 (en) * | 1991-10-24 | 1993-04-28 | Glaxo Group Limited | Benzodiazepine derivatives, and their use as antagonists of gastrin and/or cholecystokinin |
| GB2264492B (en) | 1992-02-27 | 1996-09-25 | Yamanouchi Pharma Co Ltd | Benzodiazepine derivatives |
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| GB2282594A (en) | 1993-08-25 | 1995-04-12 | Yamanouchi Pharma Co Ltd | Benzodiazepine derivatives |
| GB2282595A (en) | 1993-08-25 | 1995-04-12 | Yamanouchi Pharma Co Ltd | Benzodiazepine derivatives |
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2015
- 2015-08-07 GB GBGB1513979.3A patent/GB201513979D0/en not_active Ceased
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2016
- 2016-08-05 EP EP21165863.8A patent/EP3868746A1/en active Pending
- 2016-08-05 EP EP16751327.4A patent/EP3331865B1/en active Active
- 2016-08-05 WO PCT/GB2016/052442 patent/WO2017025727A1/en not_active Ceased
- 2016-08-05 US US15/750,339 patent/US10570102B2/en active Active
- 2016-08-05 CN CN201680045936.3A patent/CN108055843A/zh active Pending
- 2016-08-05 JP JP2018505617A patent/JP6979398B2/ja active Active
-
2020
- 2020-01-13 US US16/741,064 patent/US11447454B2/en active Active
-
2022
- 2022-08-09 US US17/818,517 patent/US20230055040A1/en not_active Abandoned
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| US5563136A (en) * | 1991-10-10 | 1996-10-08 | Rhone-Poulenc Rorer S.A. | 3-Ureidobenzodiazepinones useful as antagonists of CCK or of gastrin |
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Also Published As
| Publication number | Publication date |
|---|---|
| WO2017025727A1 (en) | 2017-02-16 |
| US20180237400A1 (en) | 2018-08-23 |
| US20200223807A1 (en) | 2020-07-16 |
| EP3331865B1 (en) | 2021-05-12 |
| US10570102B2 (en) | 2020-02-25 |
| JP6979398B2 (ja) | 2021-12-15 |
| EP3868746A1 (en) | 2021-08-25 |
| US20230055040A1 (en) | 2023-02-23 |
| HK1256411A1 (en) | 2019-09-20 |
| JP2018523660A (ja) | 2018-08-23 |
| US11447454B2 (en) | 2022-09-20 |
| EP3331865A1 (en) | 2018-06-13 |
| GB201513979D0 (en) | 2015-09-23 |
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