CA2888392A1 - Processes for preparing 3-benzazepines - Google Patents
Processes for preparing 3-benzazepines Download PDFInfo
- Publication number
- CA2888392A1 CA2888392A1 CA2888392A CA2888392A CA2888392A1 CA 2888392 A1 CA2888392 A1 CA 2888392A1 CA 2888392 A CA2888392 A CA 2888392A CA 2888392 A CA2888392 A CA 2888392A CA 2888392 A1 CA2888392 A1 CA 2888392A1
- Authority
- CA
- Canada
- Prior art keywords
- alkyl
- haloalkyl
- halo
- heteroaryl
- aryl
- 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.)
- Withdrawn
Links
- 238000000034 method Methods 0.000 title claims abstract description 347
- 230000008569 process Effects 0.000 title claims abstract description 304
- YGLDQFWPUCURIP-UHFFFAOYSA-N 3h-3-benzazepine Chemical class C1=CNC=CC2=CC=CC=C21 YGLDQFWPUCURIP-UHFFFAOYSA-N 0.000 title abstract description 8
- 150000003839 salts Chemical class 0.000 claims abstract description 160
- 125000004209 (C1-C8) alkyl group Chemical group 0.000 claims description 303
- 125000005843 halogen group Chemical group 0.000 claims description 281
- 150000001875 compounds Chemical class 0.000 claims description 272
- 125000001188 haloalkyl group Chemical group 0.000 claims description 228
- -1 hydroxy, mercapto Chemical class 0.000 claims description 217
- 125000003118 aryl group Chemical group 0.000 claims description 200
- 125000001072 heteroaryl group Chemical group 0.000 claims description 198
- 125000000753 cycloalkyl group Chemical group 0.000 claims description 194
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 128
- 125000002887 hydroxy group Chemical group [H]O* 0.000 claims description 116
- 239000003153 chemical reaction reagent Substances 0.000 claims description 108
- 125000003342 alkenyl group Chemical group 0.000 claims description 93
- 125000004178 (C1-C4) alkyl group Chemical group 0.000 claims description 92
- 239000002904 solvent Substances 0.000 claims description 87
- 125000003545 alkoxy group Chemical group 0.000 claims description 86
- 125000000623 heterocyclic group Chemical group 0.000 claims description 79
- 125000004429 atom Chemical group 0.000 claims description 73
- 125000001424 substituent group Chemical group 0.000 claims description 71
- 125000004765 (C1-C4) haloalkyl group Chemical group 0.000 claims description 70
- 125000004648 C2-C8 alkenyl group Chemical group 0.000 claims description 69
- 125000004649 C2-C8 alkynyl group Chemical group 0.000 claims description 69
- 239000003638 chemical reducing agent Substances 0.000 claims description 69
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims description 68
- 125000004183 alkoxy alkyl group Chemical group 0.000 claims description 67
- 229910052799 carbon Inorganic materials 0.000 claims description 66
- CBOIHMRHGLHBPB-UHFFFAOYSA-N hydroxymethyl Chemical compound O[CH2] CBOIHMRHGLHBPB-UHFFFAOYSA-N 0.000 claims description 65
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims description 63
- 125000002883 imidazolyl group Chemical group 0.000 claims description 62
- 239000000203 mixture Substances 0.000 claims description 61
- 239000002253 acid Substances 0.000 claims description 60
- 150000001721 carbon Chemical group 0.000 claims description 55
- 125000003710 aryl alkyl group Chemical group 0.000 claims description 54
- 125000004446 heteroarylalkyl group Chemical group 0.000 claims description 52
- VMWNQDUVQKEIOC-CYBMUJFWSA-N apomorphine Chemical compound C([C@H]1N(C)CC2)C3=CC=C(O)C(O)=C3C3=C1C2=CC=C3 VMWNQDUVQKEIOC-CYBMUJFWSA-N 0.000 claims description 43
- 125000004650 C1-C8 alkynyl group Chemical group 0.000 claims description 41
- UORVGPXVDQYIDP-UHFFFAOYSA-N borane Chemical compound B UORVGPXVDQYIDP-UHFFFAOYSA-N 0.000 claims description 37
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 claims description 37
- RFFLAFLAYFXFSW-UHFFFAOYSA-N 1,2-dichlorobenzene Chemical compound ClC1=CC=CC=C1Cl RFFLAFLAYFXFSW-UHFFFAOYSA-N 0.000 claims description 35
- 239000002841 Lewis acid Substances 0.000 claims description 35
- 229910000085 borane Inorganic materials 0.000 claims description 35
- 150000007517 lewis acids Chemical class 0.000 claims description 35
- 125000004433 nitrogen atom Chemical group N* 0.000 claims description 33
- DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 claims description 30
- 239000002244 precipitate Substances 0.000 claims description 29
- 238000004519 manufacturing process Methods 0.000 claims description 28
- CSCPPACGZOOCGX-UHFFFAOYSA-N Acetone Chemical compound CC(C)=O CSCPPACGZOOCGX-UHFFFAOYSA-N 0.000 claims description 26
- 125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 claims description 26
- 229910052782 aluminium Inorganic materials 0.000 claims description 25
- 125000004093 cyano group Chemical group *C#N 0.000 claims description 25
- 125000002541 furyl group Chemical group 0.000 claims description 25
- 125000000449 nitro group Chemical group [O-][N+](*)=O 0.000 claims description 25
- 125000003226 pyrazolyl group Chemical group 0.000 claims description 25
- 125000001544 thienyl group Chemical group 0.000 claims description 25
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 24
- 125000000592 heterocycloalkyl group Chemical group 0.000 claims description 24
- 125000000168 pyrrolyl group Chemical group 0.000 claims description 24
- VSCWAEJMTAWNJL-UHFFFAOYSA-K aluminium trichloride Chemical compound Cl[Al](Cl)Cl VSCWAEJMTAWNJL-UHFFFAOYSA-K 0.000 claims description 23
- QAOWNCQODCNURD-UHFFFAOYSA-N Sulfuric acid Chemical compound OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 claims description 22
- FEWJPZIEWOKRBE-JCYAYHJZSA-N Dextrotartaric acid Chemical compound OC(=O)[C@H](O)[C@@H](O)C(O)=O FEWJPZIEWOKRBE-JCYAYHJZSA-N 0.000 claims description 20
- JCXJVPUVTGWSNB-UHFFFAOYSA-N Nitrogen dioxide Chemical compound O=[N]=O JCXJVPUVTGWSNB-UHFFFAOYSA-N 0.000 claims description 20
- LMBFAGIMSUYTBN-MPZNNTNKSA-N teixobactin Chemical compound C([C@H](C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H](CCC(N)=O)C(=O)N[C@H]([C@@H](C)CC)C(=O)N[C@@H]([C@@H](C)CC)C(=O)N[C@@H](CO)C(=O)N[C@H]1C(N[C@@H](C)C(=O)N[C@@H](C[C@@H]2NC(=N)NC2)C(=O)N[C@H](C(=O)O[C@H]1C)[C@@H](C)CC)=O)NC)C1=CC=CC=C1 LMBFAGIMSUYTBN-MPZNNTNKSA-N 0.000 claims description 20
- 125000002023 trifluoromethyl group Chemical group FC(F)(F)* 0.000 claims description 20
- 125000004767 (C1-C4) haloalkoxy group Chemical group 0.000 claims description 19
- NNBZCPXTIHJBJL-UHFFFAOYSA-N decalin Chemical compound C1CCCC2CCCCC21 NNBZCPXTIHJBJL-UHFFFAOYSA-N 0.000 claims description 18
- 125000000229 (C1-C4)alkoxy group Chemical group 0.000 claims description 17
- 125000004423 acyloxy group Chemical group 0.000 claims description 16
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 16
- 229910052736 halogen Inorganic materials 0.000 claims description 15
- 150000002367 halogens Chemical class 0.000 claims description 15
- FEWJPZIEWOKRBE-UHFFFAOYSA-N Tartaric acid Natural products [H+].[H+].[O-]C(=O)C(O)C(O)C([O-])=O FEWJPZIEWOKRBE-UHFFFAOYSA-N 0.000 claims description 14
- 150000007979 thiazole derivatives Chemical class 0.000 claims description 14
- 125000006731 (C1-C8) thioalkoxy group Chemical group 0.000 claims description 13
- FZWLAAWBMGSTSO-UHFFFAOYSA-N Thiazole Chemical group C1=CSC=N1 FZWLAAWBMGSTSO-UHFFFAOYSA-N 0.000 claims description 13
- 150000002460 imidazoles Chemical class 0.000 claims description 13
- 150000003557 thiazoles Chemical class 0.000 claims description 13
- 125000005336 allyloxy group Chemical group 0.000 claims description 12
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical compound [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 claims description 12
- MDFFNEOEWAXZRQ-UHFFFAOYSA-N aminyl Chemical compound [NH2] MDFFNEOEWAXZRQ-UHFFFAOYSA-N 0.000 claims description 12
- 229910052987 metal hydride Inorganic materials 0.000 claims description 11
- 150000004681 metal hydrides Chemical class 0.000 claims description 11
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical group [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 10
- 150000004820 halides Chemical class 0.000 claims description 10
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 claims description 10
- 239000011975 tartaric acid Substances 0.000 claims description 9
- 235000002906 tartaric acid Nutrition 0.000 claims description 8
- 239000001358 L(+)-tartaric acid Substances 0.000 claims description 6
- 235000011002 L(+)-tartaric acid Nutrition 0.000 claims description 6
- FEWJPZIEWOKRBE-LWMBPPNESA-N L-(+)-Tartaric acid Natural products OC(=O)[C@@H](O)[C@H](O)C(O)=O FEWJPZIEWOKRBE-LWMBPPNESA-N 0.000 claims description 6
- 230000001376 precipitating effect Effects 0.000 claims description 6
- 230000000717 retained effect Effects 0.000 claims description 5
- 125000004430 oxygen atom Chemical group O* 0.000 claims 22
- 101100240516 Caenorhabditis elegans nhr-10 gene Proteins 0.000 claims 21
- 239000012454 non-polar solvent Substances 0.000 claims 6
- JYNZIOFUHBJABQ-UHFFFAOYSA-N allyl-{6-[3-(4-bromo-phenyl)-benzofuran-6-yloxy]-hexyl-}-methyl-amin Chemical compound C=1OC2=CC(OCCCCCCN(C)CC=C)=CC=C2C=1C1=CC=C(Br)C=C1 JYNZIOFUHBJABQ-UHFFFAOYSA-N 0.000 claims 1
- QZAYGJVTTNCVMB-UHFFFAOYSA-N serotonin Chemical compound C1=C(O)C=C2C(CCN)=CNC2=C1 QZAYGJVTTNCVMB-UHFFFAOYSA-N 0.000 abstract description 22
- 238000002360 preparation method Methods 0.000 abstract description 21
- 239000000543 intermediate Substances 0.000 abstract description 9
- 208000008589 Obesity Diseases 0.000 abstract description 6
- 235000020824 obesity Nutrition 0.000 abstract description 6
- 238000011282 treatment Methods 0.000 abstract description 6
- 208000015114 central nervous system disease Diseases 0.000 abstract description 4
- 239000000018 receptor agonist Substances 0.000 abstract description 3
- 229940044601 receptor agonist Drugs 0.000 abstract description 3
- 229940076279 serotonin Drugs 0.000 abstract description 3
- 125000000217 alkyl group Chemical group 0.000 description 102
- 238000006243 chemical reaction Methods 0.000 description 72
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 45
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 43
- HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 39
- 239000000243 solution Substances 0.000 description 37
- 239000000047 product Substances 0.000 description 36
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 30
- 125000000304 alkynyl group Chemical group 0.000 description 24
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 22
- 238000004895 liquid chromatography mass spectrometry Methods 0.000 description 22
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
- 230000002140 halogenating effect Effects 0.000 description 21
- 239000010410 layer Substances 0.000 description 21
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical group CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 19
- KFZMGEQAYNKOFK-UHFFFAOYSA-N Isopropanol Chemical compound CC(C)O KFZMGEQAYNKOFK-UHFFFAOYSA-N 0.000 description 19
- 238000007363 ring formation reaction Methods 0.000 description 19
- 125000006273 (C1-C3) alkyl group Chemical group 0.000 description 18
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 18
- 239000007787 solid Substances 0.000 description 18
- ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 17
- 229910015900 BF3 Inorganic materials 0.000 description 16
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 16
- WTEOIRVLGSZEPR-UHFFFAOYSA-N boron trifluoride Chemical compound FB(F)F WTEOIRVLGSZEPR-UHFFFAOYSA-N 0.000 description 16
- 239000012044 organic layer Substances 0.000 description 16
- 239000011541 reaction mixture Substances 0.000 description 16
- 238000006722 reduction reaction Methods 0.000 description 16
- 229940093499 ethyl acetate Drugs 0.000 description 15
- 235000019439 ethyl acetate Nutrition 0.000 description 15
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 15
- 230000002829 reductive effect Effects 0.000 description 15
- LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 14
- 238000005481 NMR spectroscopy Methods 0.000 description 14
- 230000009467 reduction Effects 0.000 description 13
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 11
- BZLVMXJERCGZMT-UHFFFAOYSA-N Methyl tert-butyl ether Chemical compound COC(C)(C)C BZLVMXJERCGZMT-UHFFFAOYSA-N 0.000 description 10
- 229910052739 hydrogen Inorganic materials 0.000 description 10
- 239000007858 starting material Substances 0.000 description 10
- 239000000725 suspension Substances 0.000 description 10
- 239000007789 gas Substances 0.000 description 9
- 238000001556 precipitation Methods 0.000 description 9
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
- VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical class Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 8
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 8
- 239000002585 base Substances 0.000 description 8
- 125000004432 carbon atom Chemical group C* 0.000 description 8
- 238000001816 cooling Methods 0.000 description 8
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 8
- 235000019341 magnesium sulphate Nutrition 0.000 description 8
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 7
- 101150041968 CDC13 gene Proteins 0.000 description 7
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 7
- 150000007513 acids Chemical class 0.000 description 7
- 150000001408 amides Chemical class 0.000 description 7
- 150000001412 amines Chemical class 0.000 description 7
- 239000000463 material Substances 0.000 description 7
- XKRFYHLGVUSROY-UHFFFAOYSA-N Argon Chemical compound [Ar] XKRFYHLGVUSROY-UHFFFAOYSA-N 0.000 description 6
- IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 6
- LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 6
- KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 description 6
- 230000015572 biosynthetic process Effects 0.000 description 6
- 239000002798 polar solvent Substances 0.000 description 6
- 239000000126 substance Substances 0.000 description 6
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 6
- 239000000470 constituent Substances 0.000 description 5
- 238000000605 extraction Methods 0.000 description 5
- 238000010992 reflux Methods 0.000 description 5
- 238000003756 stirring Methods 0.000 description 5
- 238000003786 synthesis reaction Methods 0.000 description 5
- 125000005309 thioalkoxy group Chemical group 0.000 description 5
- 102000006902 5-HT2C Serotonin Receptor Human genes 0.000 description 4
- 108010072553 5-HT2C Serotonin Receptor Proteins 0.000 description 4
- ZOXJGFHDIHLPTG-UHFFFAOYSA-N Boron Chemical compound [B] ZOXJGFHDIHLPTG-UHFFFAOYSA-N 0.000 description 4
- FERIUCNNQQJTOY-UHFFFAOYSA-N Butyric acid Chemical compound CCCC(O)=O FERIUCNNQQJTOY-UHFFFAOYSA-N 0.000 description 4
- AFVFQIVMOAPDHO-UHFFFAOYSA-N Methanesulfonic acid Chemical compound CS(O)(=O)=O AFVFQIVMOAPDHO-UHFFFAOYSA-N 0.000 description 4
- SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 4
- PQLAYKMGZDUDLQ-UHFFFAOYSA-K aluminium bromide Chemical compound Br[Al](Br)Br PQLAYKMGZDUDLQ-UHFFFAOYSA-K 0.000 description 4
- 238000010640 amide synthesis reaction Methods 0.000 description 4
- 238000009835 boiling Methods 0.000 description 4
- 229910052796 boron Inorganic materials 0.000 description 4
- 230000008878 coupling Effects 0.000 description 4
- 238000010168 coupling process Methods 0.000 description 4
- 238000005859 coupling reaction Methods 0.000 description 4
- YNLAOSYQHBDIKW-UHFFFAOYSA-M diethylaluminium chloride Chemical compound CC[Al](Cl)CC YNLAOSYQHBDIKW-UHFFFAOYSA-M 0.000 description 4
- CSJLBAMHHLJAAS-UHFFFAOYSA-N diethylaminosulfur trifluoride Chemical compound CCN(CC)S(F)(F)F CSJLBAMHHLJAAS-UHFFFAOYSA-N 0.000 description 4
- 208000037265 diseases, disorders, signs and symptoms Diseases 0.000 description 4
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- 229910052751 metal Inorganic materials 0.000 description 4
- 239000002184 metal Substances 0.000 description 4
- YSTQWZZQKCCBAY-UHFFFAOYSA-L methylaluminum(2+);dichloride Chemical compound C[Al](Cl)Cl YSTQWZZQKCCBAY-UHFFFAOYSA-L 0.000 description 4
- 150000007522 mineralic acids Chemical class 0.000 description 4
- 150000007524 organic acids Chemical class 0.000 description 4
- IPNPIHIZVLFAFP-UHFFFAOYSA-N phosphorus tribromide Chemical compound BrP(Br)Br IPNPIHIZVLFAFP-UHFFFAOYSA-N 0.000 description 4
- 238000012827 research and development Methods 0.000 description 4
- 125000001273 sulfonato group Chemical group [O-]S(*)(=O)=O 0.000 description 4
- HFRXJVQOXRXOPP-UHFFFAOYSA-N thionyl bromide Chemical group BrS(Br)=O HFRXJVQOXRXOPP-UHFFFAOYSA-N 0.000 description 4
- JOXIMZWYDAKGHI-UHFFFAOYSA-N toluene-4-sulfonic acid Chemical compound CC1=CC=C(S(O)(=O)=O)C=C1 JOXIMZWYDAKGHI-UHFFFAOYSA-N 0.000 description 4
- PBKONEOXTCPAFI-UHFFFAOYSA-N 1,2,4-trichlorobenzene Chemical compound ClC1=CC=C(Cl)C(Cl)=C1 PBKONEOXTCPAFI-UHFFFAOYSA-N 0.000 description 3
- YAFMYKFAUNCQPU-UHFFFAOYSA-N 1-(2-bromoethyl)-4-chlorobenzene Chemical compound ClC1=CC=C(CCBr)C=C1 YAFMYKFAUNCQPU-UHFFFAOYSA-N 0.000 description 3
- QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
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- LSPHULWDVZXLIL-UHFFFAOYSA-N Camphoric acid Natural products CC1(C)C(C(O)=O)CCC1(C)C(O)=O LSPHULWDVZXLIL-UHFFFAOYSA-N 0.000 description 3
- WWZKQHOCKIZLMA-UHFFFAOYSA-N Caprylic acid Natural products CCCCCCCC(O)=O WWZKQHOCKIZLMA-UHFFFAOYSA-N 0.000 description 3
- LYCAIKOWRPUZTN-UHFFFAOYSA-N Ethylene glycol Chemical compound OCCO LYCAIKOWRPUZTN-UHFFFAOYSA-N 0.000 description 3
- PEDCQBHIVMGVHV-UHFFFAOYSA-N Glycerine Chemical compound OCC(O)CO PEDCQBHIVMGVHV-UHFFFAOYSA-N 0.000 description 3
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- FXHOOIRPVKKKFG-UHFFFAOYSA-N N,N-Dimethylacetamide Chemical compound CN(C)C(C)=O FXHOOIRPVKKKFG-UHFFFAOYSA-N 0.000 description 3
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- XAGFODPZIPBFFR-UHFFFAOYSA-N aluminium Chemical compound [Al] XAGFODPZIPBFFR-UHFFFAOYSA-N 0.000 description 3
- 229910052786 argon Inorganic materials 0.000 description 3
- 125000004104 aryloxy group Chemical group 0.000 description 3
- BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 3
- LSPHULWDVZXLIL-QUBYGPBYSA-N camphoric acid Chemical compound CC1(C)[C@H](C(O)=O)CC[C@]1(C)C(O)=O LSPHULWDVZXLIL-QUBYGPBYSA-N 0.000 description 3
- 239000003795 chemical substances by application Substances 0.000 description 3
- 239000012043 crude product Substances 0.000 description 3
- MTHSVFCYNBDYFN-UHFFFAOYSA-N diethylene glycol Chemical compound OCCOCCO MTHSVFCYNBDYFN-UHFFFAOYSA-N 0.000 description 3
- JGHYBJVUQGTEEB-UHFFFAOYSA-M dimethylalumanylium;chloride Chemical compound C[Al](C)Cl JGHYBJVUQGTEEB-UHFFFAOYSA-M 0.000 description 3
- 229910001873 dinitrogen Inorganic materials 0.000 description 3
- UAIZDWNSWGTKFZ-UHFFFAOYSA-L ethylaluminum(2+);dichloride Chemical compound CC[Al](Cl)Cl UAIZDWNSWGTKFZ-UHFFFAOYSA-L 0.000 description 3
- 238000001914 filtration Methods 0.000 description 3
- 238000010438 heat treatment Methods 0.000 description 3
- 125000005842 heteroatom Chemical group 0.000 description 3
- BHEPBYXIRTUNPN-UHFFFAOYSA-N hydridophosphorus(.) (triplet) Chemical compound [PH] BHEPBYXIRTUNPN-UHFFFAOYSA-N 0.000 description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- 239000012442 inert solvent Substances 0.000 description 3
- 230000008018 melting Effects 0.000 description 3
- 238000002844 melting Methods 0.000 description 3
- OFBQJSOFQDEBGM-UHFFFAOYSA-N n-pentane Natural products CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 3
- 229910052757 nitrogen Inorganic materials 0.000 description 3
- 235000011007 phosphoric acid Nutrition 0.000 description 3
- BDERNNFJNOPAEC-UHFFFAOYSA-N propan-1-ol Chemical compound CCCO BDERNNFJNOPAEC-UHFFFAOYSA-N 0.000 description 3
- 125000006239 protecting group Chemical group 0.000 description 3
- 239000000376 reactant Substances 0.000 description 3
- 102000005962 receptors Human genes 0.000 description 3
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Landscapes
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Applications Claiming Priority (5)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US47928003P | 2003-06-17 | 2003-06-17 | |
| US60/479,280 | 2003-06-17 | ||
| US51296703P | 2003-10-21 | 2003-10-21 | |
| US60/512,967 | 2003-10-21 | ||
| CA2529401A CA2529401C (en) | 2003-06-17 | 2004-06-16 | Processes for preparing 3-benzazepines |
Related Parent Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2529401A Division CA2529401C (en) | 2003-06-17 | 2004-06-16 | Processes for preparing 3-benzazepines |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| CA2888392A1 true CA2888392A1 (en) | 2005-03-03 |
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ID=33563791
Family Applications (2)
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| CA2529320A Expired - Fee Related CA2529320C (en) | 2003-06-17 | 2004-06-16 | Benzazepine derivatives useful for the treatment of 5ht2c receptor associated diseases |
| CA2888392A Withdrawn CA2888392A1 (en) | 2003-06-17 | 2004-06-16 | Processes for preparing 3-benzazepines |
Family Applications Before (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| CA2529320A Expired - Fee Related CA2529320C (en) | 2003-06-17 | 2004-06-16 | Benzazepine derivatives useful for the treatment of 5ht2c receptor associated diseases |
Country Status (14)
| Country | Link |
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| US (3) | US7704993B2 (enExample) |
| EP (2) | EP2332920A3 (enExample) |
| JP (2) | JP4782003B2 (enExample) |
| KR (1) | KR101152521B1 (enExample) |
| CN (4) | CN101792417A (enExample) |
| AU (1) | AU2004253888B2 (enExample) |
| BR (1) | BRPI0411470A (enExample) |
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| EA (1) | EA016558B1 (enExample) |
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| WO (1) | WO2005003096A1 (enExample) |
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Families Citing this family (52)
| Publication number | Priority date | Publication date | Assignee | Title |
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| US6953787B2 (en) | 2002-04-12 | 2005-10-11 | Arena Pharmaceuticals, Inc. | 5HT2C receptor modulators |
| DK2332921T3 (en) * | 2003-06-17 | 2016-05-09 | Arena Pharm Inc | 8-Chloro-1-methyl-2,3,4,5-tetrahydro-1H-3benzazepine hydrochloride |
| JP4782003B2 (ja) | 2003-06-17 | 2011-09-28 | アリーナ ファーマシューティカルズ， インコーポレイテッド | ５ｈｔ２ｃレセプター関連疾患の処置に有用なベンズアゼピン誘導体 |
| US20070275949A1 (en) * | 2003-10-22 | 2007-11-29 | Arena Pharmaceuticals, Inc. | Benzazepine Derivatives and Methods of Prophylaxis or Treatment of 5Ht2C Receptor Associated Diseases |
| EP1792629A4 (en) | 2004-08-25 | 2010-08-25 | Takeda Pharmaceutical | MEANS FOR THE PREVENTION / TREATMENT OF STRESS-RELATED HARNINE INCONTINENCE AND PRECAUTIONARY METHOD FOR THIS |
| RS50996B (sr) | 2004-12-21 | 2010-10-31 | Arena Pharmaceuticals Inc. | Kristalni oblici (r)-8-hloro-1-metil-2,3,4,5-tetrahidro-1h-benzazepin hlorhidrat |
| KR101519441B1 (ko) | 2004-12-23 | 2015-05-12 | 아레나 파마슈티칼스, 인크. | 5ｈｔ２ｃ 수용체 조정물질 조성물 및 그의 사용 방법 |
| PT1924560E (pt) * | 2005-09-01 | 2009-10-23 | Lilly Co Eli | 2,3,4,5-tetra-hidro-1h-benzo[d]azepinas como agonistas de receptores 5-ht2c |
| ES2397400T3 (es) | 2005-09-01 | 2013-03-06 | Eli Lilly & Company | 6-arilalquilamino-2,3,4,5-tetrahidro-1H-benzo[D]azepinas como agonistas del receptor 5-HT2C |
| BRPI0615033A2 (pt) | 2005-09-01 | 2011-04-26 | Lilly Co Eli | composto, composição farmacêutica, e, uso de um composto |
| WO2007028132A2 (en) | 2005-09-01 | 2007-03-08 | Eli Lilly And Company | 6-N-LINKED HETEROCYCLE-SUBSTITUTED 2,3,4,5-TETRAHYDRO-1H-BENZO[d]AZEPINES AS 5-HT2C RECEPTOR AGONISTS |
| MX2008009178A (es) | 2006-01-19 | 2008-12-05 | Athersys Inc | Tiofenil y pirrolil acepinas como ligandos del receptor de serotonina 5-ht2c y sus usos. |
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- 2004-06-16 EA EA200600048A patent/EA016558B1/ru not_active IP Right Cessation
- 2004-06-16 CN CN201010003763A patent/CN101792417A/zh active Pending
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- 2004-06-16 BR BRPI0411470-1A patent/BRPI0411470A/pt active Search and Examination
- 2004-06-16 CN CN2004800167803A patent/CN1805939B/zh not_active Expired - Lifetime
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