CA1332169C - Procede pour la preparation de composes pyridyniques a anneaux condenses - Google Patents

Procede pour la preparation de composes pyridyniques a anneaux condenses

Info

Publication number: CA1332169C
Authority: CA; Canada
Prior art keywords: formula; process according; amino; hydrogen; compound
Prior art date: 1986-10-20
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.): Expired - Fee Related

Application number

CA000616047A

Other languages

English (en)

Inventor

George S. K. Wong

Edward C. Taylor

Current Assignee (The listed assignees may be inaccurate. Google has not performed a legal analysis and makes no representation or warranty as to the accuracy of the list.)

Princeton University

Original Assignee

Princeton University

Priority date (The priority date 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 date listed.)

1986-10-20

Filing date

1991-04-19

Publication date

1994-09-27

1986-10-20 Priority claimed from US06/922,511 external-priority patent/US4818819A/en

1991-04-19 Application filed by Princeton University filed Critical Princeton University

1991-04-19 Priority to CA000616047A priority Critical patent/CA1332169C/fr

1994-09-27 Application granted granted Critical

1994-09-27 Publication of CA1332169C publication Critical patent/CA1332169C/fr

2007-10-19 Anticipated expiration legal-status Critical

Status Expired - Fee Related legal-status Critical Current

Links

238000000034 method Methods 0.000 title claims abstract description 31
230000008569 process Effects 0.000 title claims abstract description 24
238000002360 preparation method Methods 0.000 title abstract description 6
150000003222 pyridines Chemical class 0.000 title description 3
150000001875 compounds Chemical class 0.000 claims abstract description 51
KDLHZDBZIXYQEI-UHFFFAOYSA-N Palladium Chemical compound [Pd] KDLHZDBZIXYQEI-UHFFFAOYSA-N 0.000 claims abstract description 25
JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical class C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims abstract description 24
229910052763 palladium Inorganic materials 0.000 claims abstract description 14
238000006243 chemical reaction Methods 0.000 claims abstract description 12
239000003054 catalyst Substances 0.000 claims abstract description 8
150000002148 esters Chemical class 0.000 claims abstract description 4
WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 claims description 28
229910052739 hydrogen Inorganic materials 0.000 claims description 28
239000001257 hydrogen Substances 0.000 claims description 28
125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 claims description 21
-1 palladium halide salt Chemical class 0.000 claims description 17
125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 claims description 16
125000006239 protecting group Chemical group 0.000 claims description 16
125000004432 carbon atom Chemical group C* 0.000 claims description 14
125000002924 primary amino group Chemical group [H]N([H])* 0.000 claims description 14
UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims description 12
UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 11
239000002904 solvent Substances 0.000 claims description 11
125000002346 iodo group Chemical group I* 0.000 claims description 10
125000001246 bromo group Chemical group Br* 0.000 claims description 9
125000006244 carboxylic acid protecting group Chemical group 0.000 claims description 9
ZRALSGWEFCBTJO-UHFFFAOYSA-N Guanidine Chemical compound NC(N)=N ZRALSGWEFCBTJO-UHFFFAOYSA-N 0.000 claims description 8
239000011203 carbon fibre reinforced carbon Substances 0.000 claims description 8
150000002431 hydrogen Chemical class 0.000 claims description 8
125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 8
229960002989 glutamic acid Drugs 0.000 claims description 7
125000003545 alkoxy group Chemical group 0.000 claims description 5
125000000217 alkyl group Chemical group 0.000 claims description 5
CHJJGSNFBQVOTG-UHFFFAOYSA-N N-methyl-guanidine Natural products CNC(N)=N CHJJGSNFBQVOTG-UHFFFAOYSA-N 0.000 claims description 4
SWSQBOPZIKWTGO-UHFFFAOYSA-N dimethylaminoamidine Natural products CN(C)C(N)=N SWSQBOPZIKWTGO-UHFFFAOYSA-N 0.000 claims description 4
YQTCQNIPQMJNTI-UHFFFAOYSA-N 2,2-dimethylpropan-1-one Chemical group CC(C)(C)[C]=O YQTCQNIPQMJNTI-UHFFFAOYSA-N 0.000 claims description 2
125000004644 alkyl sulfinyl group Chemical group 0.000 claims description 2
125000004414 alkyl thio group Chemical group 0.000 claims description 2
125000003118 aryl group Chemical group 0.000 claims description 2
125000005110 aryl thio group Chemical group 0.000 claims description 2
125000001309 chloro group Chemical group Cl* 0.000 claims description 2
UDJFFSGCRRMVFH-UHFFFAOYSA-N pyrido[2,3-d]pyrimidine Chemical compound N1=CN=CC2=CC=CN=C21 UDJFFSGCRRMVFH-UHFFFAOYSA-N 0.000 claims description 2
125000003396 thiol group Chemical class [H]S* 0.000 claims description 2
RZADWTQXPPHNCZ-UHFFFAOYSA-N 4-[2-(2-amino-4-oxo-5,6,7,8-tetrahydro-1h-pyrido[2,3-d]pyrimidin-6-yl)ethyl]benzoic acid Chemical compound C1NC2=NC(N)=NC(O)=C2CC1CCC1=CC=C(C(O)=O)C=C1 RZADWTQXPPHNCZ-UHFFFAOYSA-N 0.000 claims 1
125000001589 carboacyl group Chemical group 0.000 claims 1
239000007795 chemical reaction product Substances 0.000 claims 1
VILAVOFMIJHSJA-UHFFFAOYSA-N dicarbon monoxide Chemical group [C]=C=O VILAVOFMIJHSJA-UHFFFAOYSA-N 0.000 claims 1
239000000543 intermediate Substances 0.000 abstract description 6
229940034982 antineoplastic agent Drugs 0.000 abstract description 2
239000002246 antineoplastic agent Substances 0.000 abstract description 2
239000000126 substance Substances 0.000 abstract description 2
SCGCLYHLGBFKIB-UHFFFAOYSA-N 2-amino-6-ethynyl-1h-pyrido[2,3-d]pyrimidin-4-one Chemical compound C1=C(C#C)C=NC2=NC(N)=NC(O)=C21 SCGCLYHLGBFKIB-UHFFFAOYSA-N 0.000 abstract 1
GHICCUXQJBDNRN-UHFFFAOYSA-N 4-iodobenzoic acid Chemical compound OC(=O)C1=CC=C(I)C=C1 GHICCUXQJBDNRN-UHFFFAOYSA-N 0.000 abstract 1
159000000018 pyrido[2,3-d]pyrimidines Chemical class 0.000 abstract 1
150000003230 pyrimidines Chemical class 0.000 abstract 1
YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 63
OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 39
239000000203 mixture Substances 0.000 description 33
239000007787 solid Substances 0.000 description 26
IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 24
238000005481 NMR spectroscopy Methods 0.000 description 24
CZPWVGJYEJSRLH-UHFFFAOYSA-N Pyrimidine Chemical compound C1=CN=CN=C1 CZPWVGJYEJSRLH-UHFFFAOYSA-N 0.000 description 24
ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 21
229940073584 methylene chloride Drugs 0.000 description 21
101150041968 CDC13 gene Proteins 0.000 description 20
HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 20
125000004177 diethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 17
239000011541 reaction mixture Substances 0.000 description 15
LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 13
XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 12
229910052757 nitrogen Inorganic materials 0.000 description 12
VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 11
125000003236 benzoyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C(*)=O 0.000 description 11
238000010992 reflux Methods 0.000 description 11
IAZDPXIOMUYVGZ-WFGJKAKNSA-N Dimethyl sulfoxide Chemical compound [2H]C([2H])([2H])S(=O)C([2H])([2H])[2H] IAZDPXIOMUYVGZ-WFGJKAKNSA-N 0.000 description 10
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 10
UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 9
239000003480 eluent Substances 0.000 description 9
XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 9
RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 8
239000000741 silica gel Substances 0.000 description 8
229910002027 silica gel Inorganic materials 0.000 description 8
PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 7
125000004943 pyrimidin-6-yl group Chemical group N1=CN=CC=C1* 0.000 description 7
229940086542 triethylamine Drugs 0.000 description 7
VEXZGXHMUGYJMC-UHFFFAOYSA-N Hydrochloric acid Chemical compound Cl VEXZGXHMUGYJMC-UHFFFAOYSA-N 0.000 description 6
ZMXDDKWLCZADIW-UHFFFAOYSA-N N,N-Dimethylformamide Chemical compound CN(C)C=O ZMXDDKWLCZADIW-UHFFFAOYSA-N 0.000 description 6
WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 6
239000002253 acid Substances 0.000 description 6
PIBWKRNGBLPSSY-UHFFFAOYSA-L palladium(II) chloride Chemical compound Cl[Pd]Cl PIBWKRNGBLPSSY-UHFFFAOYSA-L 0.000 description 6
XHXFXVLFKHQFAL-UHFFFAOYSA-N phosphoryl trichloride Chemical compound ClP(Cl)(Cl)=O XHXFXVLFKHQFAL-UHFFFAOYSA-N 0.000 description 6
238000003756 stirring Methods 0.000 description 6
229910021595 Copper(I) iodide Inorganic materials 0.000 description 5
230000015572 biosynthetic process Effects 0.000 description 5
238000001816 cooling Methods 0.000 description 5
LSXDOTMGLUJQCM-UHFFFAOYSA-M copper(i) iodide Chemical compound I[Cu] LSXDOTMGLUJQCM-UHFFFAOYSA-M 0.000 description 5
239000000706 filtrate Substances 0.000 description 5
XJAILSCNCPJQPH-UHFFFAOYSA-N methyl 2-chloro-5-iodopyridine-3-carboxylate Chemical compound COC(=O)C1=CC(I)=CN=C1Cl XJAILSCNCPJQPH-UHFFFAOYSA-N 0.000 description 5
125000000325 methylidene group Chemical group [H]C([H])=* 0.000 description 5
FWAUARVBLKIMRS-UHFFFAOYSA-N tert-butyl 4-ethynylbenzoate Chemical compound CC(C)(C)OC(=O)C1=CC=C(C#C)C=C1 FWAUARVBLKIMRS-UHFFFAOYSA-N 0.000 description 5
LQZMLBORDGWNPD-UHFFFAOYSA-N N-iodosuccinimide Chemical compound IN1C(=O)CCC1=O LQZMLBORDGWNPD-UHFFFAOYSA-N 0.000 description 4
DTQVDTLACAAQTR-UHFFFAOYSA-N Trifluoroacetic acid Chemical compound OC(=O)C(F)(F)F DTQVDTLACAAQTR-UHFFFAOYSA-N 0.000 description 4
HSFWRNGVRCDJHI-UHFFFAOYSA-N alpha-acetylene Natural products C#C HSFWRNGVRCDJHI-UHFFFAOYSA-N 0.000 description 4
238000004587 chromatography analysis Methods 0.000 description 4
125000002534 ethynyl group Chemical group [H]C#C* 0.000 description 4
238000001704 evaporation Methods 0.000 description 4
230000008020 evaporation Effects 0.000 description 4
238000001914 filtration Methods 0.000 description 4
238000005984 hydrogenation reaction Methods 0.000 description 4
230000007062 hydrolysis Effects 0.000 description 4
238000006460 hydrolysis reaction Methods 0.000 description 4
VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical class CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
239000012299 nitrogen atmosphere Substances 0.000 description 4
239000003921 oil Substances 0.000 description 4
238000003786 synthesis reaction Methods 0.000 description 4
QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 description 3
WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 description 3
VEXZGXHMUGYJMC-UHFFFAOYSA-M Chloride anion Chemical compound [Cl-] VEXZGXHMUGYJMC-UHFFFAOYSA-M 0.000 description 3
WHUUTDBJXJRKMK-VKHMYHEASA-N L-glutamic acid Chemical compound OC(=O)[C@@H](N)CCC(O)=O WHUUTDBJXJRKMK-VKHMYHEASA-N 0.000 description 3
SJRJJKPEHAURKC-UHFFFAOYSA-N N-Methylmorpholine Chemical compound CN1CCOCC1 SJRJJKPEHAURKC-UHFFFAOYSA-N 0.000 description 3
HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 description 3
150000001412 amines Chemical class 0.000 description 3
229940076134 benzene Drugs 0.000 description 3
150000001732 carboxylic acid derivatives Chemical class 0.000 description 3
238000009833 condensation Methods 0.000 description 3
230000005494 condensation Effects 0.000 description 3
HERPVHLYIHBEFW-ZETCQYMHSA-N diethyl (2s)-2-aminopentanedioate Chemical compound CCOC(=O)CC[C@H](N)C(=O)OCC HERPVHLYIHBEFW-ZETCQYMHSA-N 0.000 description 3
239000000499 gel Substances 0.000 description 3
IXCSERBJSXMMFS-UHFFFAOYSA-N hydrogen chloride Substances Cl.Cl IXCSERBJSXMMFS-UHFFFAOYSA-N 0.000 description 3
229910000041 hydrogen chloride Inorganic materials 0.000 description 3
239000000463 material Substances 0.000 description 3
LYGJENNIWJXYER-UHFFFAOYSA-N nitromethane Chemical compound C[N+]([O-])=O LYGJENNIWJXYER-UHFFFAOYSA-N 0.000 description 3
150000002940 palladium Chemical class 0.000 description 3
125000001997 phenyl group Chemical group [H]C1=C([H])C([H])=C(*)C([H])=C1[H] 0.000 description 3
239000000376 reactant Substances 0.000 description 3
125000003808 silyl group Chemical group [H][Si]([H])([H])[*] 0.000 description 3
BFJJYXUCGYOXDM-UHFFFAOYSA-N tert-butyl 4-bromobenzoate Chemical compound CC(C)(C)OC(=O)C1=CC=C(Br)C=C1 BFJJYXUCGYOXDM-UHFFFAOYSA-N 0.000 description 3
YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 3
238000010626 work up procedure Methods 0.000 description 3
KWGRBVOPPLSCSI-WPRPVWTQSA-N (-)-ephedrine Chemical compound CN[C@@H](C)[C@H](O)C1=CC=CC=C1 KWGRBVOPPLSCSI-WPRPVWTQSA-N 0.000 description 2
GOJUJUVQIVIZAV-UHFFFAOYSA-N 2-amino-4,6-dichloropyrimidine-5-carbaldehyde Chemical group NC1=NC(Cl)=C(C=O)C(Cl)=N1 GOJUJUVQIVIZAV-UHFFFAOYSA-N 0.000 description 2
SURMYNZXHKLDFO-UHFFFAOYSA-N 2-bromopropanedial Chemical compound O=CC(Br)C=O SURMYNZXHKLDFO-UHFFFAOYSA-N 0.000 description 2
VHYFNPMBLIVWCW-UHFFFAOYSA-N 4-Dimethylaminopyridine Chemical compound CN(C)C1=CC=NC=C1 VHYFNPMBLIVWCW-UHFFFAOYSA-N 0.000 description 2
HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
SECXISVLQFMRJM-UHFFFAOYSA-N N-Methylpyrrolidone Chemical compound CN1CCCC1=O SECXISVLQFMRJM-UHFFFAOYSA-N 0.000 description 2
PCLIMKBDDGJMGD-UHFFFAOYSA-N N-bromosuccinimide Chemical compound BrN1C(=O)CCC1=O PCLIMKBDDGJMGD-UHFFFAOYSA-N 0.000 description 2
DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 2
HTZCNXWZYVXIMZ-UHFFFAOYSA-M benzyl(triethyl)azanium;chloride Chemical compound [Cl-].CC[N+](CC)(CC)CC1=CC=CC=C1 HTZCNXWZYVXIMZ-UHFFFAOYSA-M 0.000 description 2
CREMABGTGYGIQB-UHFFFAOYSA-N carbon carbon Chemical compound C.C CREMABGTGYGIQB-UHFFFAOYSA-N 0.000 description 2
239000007789 gas Substances 0.000 description 2
239000004220 glutamic acid Substances 0.000 description 2
150000002306 glutamic acid derivatives Chemical class 0.000 description 2
150000005748 halopyridines Chemical class 0.000 description 2
BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Chemical compound [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 2
239000000843 powder Substances 0.000 description 2
239000000047 product Substances 0.000 description 2
238000001953 recrystallisation Methods 0.000 description 2
150000003839 salts Chemical class 0.000 description 2
229920006395 saturated elastomer Polymers 0.000 description 2
239000007858 starting material Substances 0.000 description 2
229910052717 sulfur Inorganic materials 0.000 description 2
239000000725 suspension Substances 0.000 description 2
CWMFRHBXRUITQE-UHFFFAOYSA-N trimethylsilylacetylene Chemical group C[Si](C)(C)C#C CWMFRHBXRUITQE-UHFFFAOYSA-N 0.000 description 2
NDTYTMIUWGWIMO-SNVBAGLBSA-N (-)-perillyl alcohol Chemical compound CC(=C)[C@H]1CCC(CO)=CC1 NDTYTMIUWGWIMO-SNVBAGLBSA-N 0.000 description 1
GHPYJLCQYMAXGG-WCCKRBBISA-N (2R)-2-amino-3-(2-boronoethylsulfanyl)propanoic acid hydrochloride Chemical compound Cl.N[C@@H](CSCCB(O)O)C(O)=O GHPYJLCQYMAXGG-WCCKRBBISA-N 0.000 description 1
238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
PGZVFRAEAAXREB-UHFFFAOYSA-N 2,2-dimethylpropanoyl 2,2-dimethylpropanoate Chemical compound CC(C)(C)C(=O)OC(=O)C(C)(C)C PGZVFRAEAAXREB-UHFFFAOYSA-N 0.000 description 1
SWELIMKTDYHAOY-UHFFFAOYSA-N 2,4-diamino-6-hydroxypyrimidine Chemical compound NC1=CC(=O)N=C(N)N1 SWELIMKTDYHAOY-UHFFFAOYSA-N 0.000 description 1
UEYQJQVBUVAELZ-UHFFFAOYSA-N 2-Hydroxynicotinic acid Chemical compound OC(=O)C1=CC=CN=C1O UEYQJQVBUVAELZ-UHFFFAOYSA-N 0.000 description 1
125000004493 2-methylbut-1-yl group Chemical group CC(C*)CC 0.000 description 1
RXXCIBALSKQCAE-UHFFFAOYSA-N 3-methylbutoxymethylbenzene Chemical compound CC(C)CCOCC1=CC=CC=C1 RXXCIBALSKQCAE-UHFFFAOYSA-N 0.000 description 1
DENKGPBHLYFNGK-UHFFFAOYSA-N 4-bromobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(Br)C=C1 DENKGPBHLYFNGK-UHFFFAOYSA-N 0.000 description 1
SJXHLZCPDZPBPW-UHFFFAOYSA-M 4-ethynylbenzoate Chemical compound [O-]C(=O)C1=CC=C(C#C)C=C1 SJXHLZCPDZPBPW-UHFFFAOYSA-M 0.000 description 1
SJXHLZCPDZPBPW-UHFFFAOYSA-N 4-ethynylbenzoic acid Chemical compound OC(=O)C1=CC=C(C#C)C=C1 SJXHLZCPDZPBPW-UHFFFAOYSA-N 0.000 description 1
WULXGCDMVLQZBT-UHFFFAOYSA-N 4-iodo-1-methoxy-2-nitrobenzene Chemical compound COC1=CC=C(I)C=C1[N+]([O-])=O WULXGCDMVLQZBT-UHFFFAOYSA-N 0.000 description 1
NJAKCIUOTIPYED-UHFFFAOYSA-N 4-iodobenzoyl chloride Chemical compound ClC(=O)C1=CC=C(I)C=C1 NJAKCIUOTIPYED-UHFFFAOYSA-N 0.000 description 1
125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
GYXOTADLHQJPIP-UHFFFAOYSA-N 5-bromo-2-oxo-1h-pyridine-3-carboxylic acid Chemical compound OC(=O)C1=CC(Br)=CNC1=O GYXOTADLHQJPIP-UHFFFAOYSA-N 0.000 description 1
QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 description 1
OMPJBNCRMGITSC-UHFFFAOYSA-N Benzoylperoxide Chemical compound C=1C=CC=CC=1C(=O)OOC(=O)C1=CC=CC=C1 OMPJBNCRMGITSC-UHFFFAOYSA-N 0.000 description 1
229910021591 Copper(I) chloride Inorganic materials 0.000 description 1
KRHYYFGTRYWZRS-UHFFFAOYSA-M Fluoride anion Chemical compound [F-] KRHYYFGTRYWZRS-UHFFFAOYSA-M 0.000 description 1
WHUUTDBJXJRKMK-UHFFFAOYSA-N Glutamic acid Natural products OC(=O)C(N)CCC(O)=O WHUUTDBJXJRKMK-UHFFFAOYSA-N 0.000 description 1
DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 1
125000003338 L-glutaminyl group Chemical group O=C([*])[C@](N([H])[H])([H])C([H])([H])C([H])([H])C(=O)N([H])[H] 0.000 description 1
WSMYVTOQOOLQHP-UHFFFAOYSA-N Malondialdehyde Chemical compound O=CCC=O WSMYVTOQOOLQHP-UHFFFAOYSA-N 0.000 description 1
208000036366 Sensation of pressure Diseases 0.000 description 1
UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical class [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 1
FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
BHIIGRBMZRSDRI-UHFFFAOYSA-N [chloro(phenoxy)phosphoryl]oxybenzene Chemical compound C=1C=CC=CC=1OP(=O)(Cl)OC1=CC=CC=C1 BHIIGRBMZRSDRI-UHFFFAOYSA-N 0.000 description 1
125000002777 acetyl group Chemical group [H]C([H])([H])C(*)=O 0.000 description 1
230000009471 action Effects 0.000 description 1
230000004913 activation Effects 0.000 description 1
125000002252 acyl group Chemical group 0.000 description 1
230000010933 acylation Effects 0.000 description 1
238000005917 acylation reaction Methods 0.000 description 1
150000001336 alkenes Chemical class 0.000 description 1
125000003342 alkenyl group Chemical group 0.000 description 1
150000001345 alkine derivatives Chemical class 0.000 description 1
125000000304 alkynyl group Chemical group 0.000 description 1
150000004808 allyl alcohols Chemical class 0.000 description 1
WUOACPNHFRMFPN-UHFFFAOYSA-N alpha-terpineol Chemical compound CC1=CCC(C(C)(C)O)CC1 WUOACPNHFRMFPN-UHFFFAOYSA-N 0.000 description 1
150000008064 anhydrides Chemical class 0.000 description 1
150000001502 aryl halides Chemical class 0.000 description 1
239000012298 atmosphere Substances 0.000 description 1
230000008901 benefit Effects 0.000 description 1
150000001558 benzoic acid derivatives Chemical group 0.000 description 1
125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 description 1
238000009903 catalytic hydrogenation reaction Methods 0.000 description 1
150000001768 cations Chemical class 0.000 description 1
238000005660 chlorination reaction Methods 0.000 description 1
239000012230 colorless oil Substances 0.000 description 1
238000004440 column chromatography Methods 0.000 description 1
239000012141 concentrate Substances 0.000 description 1
235000008504 concentrate Nutrition 0.000 description 1
OXBLHERUFWYNTN-UHFFFAOYSA-M copper(I) chloride Chemical compound [Cu]Cl OXBLHERUFWYNTN-UHFFFAOYSA-M 0.000 description 1
238000005859 coupling reaction Methods 0.000 description 1
229940045803 cuprous chloride Drugs 0.000 description 1
KWGRBVOPPLSCSI-UHFFFAOYSA-N d-ephedrine Natural products CNC(C)C(O)C1=CC=CC=C1 KWGRBVOPPLSCSI-UHFFFAOYSA-N 0.000 description 1
108700041286 delta Proteins 0.000 description 1
WSEQLMQNPBNMSL-FJXQXJEOSA-N diethyl (2s)-2-aminopentanedioate;hydron;chloride Chemical compound Cl.CCOC(=O)CC[C@H](N)C(=O)OCC WSEQLMQNPBNMSL-FJXQXJEOSA-N 0.000 description 1
HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
GGSUCNLOZRCGPQ-UHFFFAOYSA-N diethylaniline Chemical compound CCN(CC)C1=CC=CC=C1 GGSUCNLOZRCGPQ-UHFFFAOYSA-N 0.000 description 1
125000000118 dimethyl group Chemical group [H]C([H])([H])* 0.000 description 1
125000005982 diphenylmethyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])(*)C1=C([H])C([H])=C([H])C([H])=C1[H] 0.000 description 1
239000003814 drug Substances 0.000 description 1
229960002179 ephedrine Drugs 0.000 description 1
230000032050 esterification Effects 0.000 description 1
238000005886 esterification reaction Methods 0.000 description 1
JCVOJRBBSLXEEJ-UHFFFAOYSA-N ethyl 2-chloro-5-iodopyridine-3-carboxylate Chemical compound CCOC(=O)C1=CC(I)=CN=C1Cl JCVOJRBBSLXEEJ-UHFFFAOYSA-N 0.000 description 1
RRXOVXUHTGDSAA-UHFFFAOYSA-N ethyl 2-oxo-1h-pyridine-3-carboxylate Chemical compound CCOC(=O)C1=CC=CN=C1O RRXOVXUHTGDSAA-UHFFFAOYSA-N 0.000 description 1
OAYLNYINCPYISS-UHFFFAOYSA-N ethyl acetate;hexane Chemical class CCCCCC.CCOC(C)=O OAYLNYINCPYISS-UHFFFAOYSA-N 0.000 description 1
239000000284 extract Substances 0.000 description 1
235000013922 glutamic acid Nutrition 0.000 description 1
125000000291 glutamic acid group Chemical group N[C@@H](CCC(O)=O)C(=O)* 0.000 description 1
150000004820 halides Chemical class 0.000 description 1
125000000623 heterocyclic group Chemical group 0.000 description 1
238000007327 hydrogenolysis reaction Methods 0.000 description 1
239000002198 insoluble material Substances 0.000 description 1
SILBTMNCGYLTOK-UHFFFAOYSA-N methyl 2-oxo-1h-pyridine-3-carboxylate Chemical compound COC(=O)C1=CC=CN=C1O SILBTMNCGYLTOK-UHFFFAOYSA-N 0.000 description 1
MOMQDEDQGJAKII-UHFFFAOYSA-N methyl 5-bromo-2-chloropyridine-3-carboxylate Chemical compound COC(=O)C1=CC(Br)=CN=C1Cl MOMQDEDQGJAKII-UHFFFAOYSA-N 0.000 description 1
TXZVFXMZHYRSDN-UHFFFAOYSA-N methyl 5-bromo-2-oxo-1h-pyridine-3-carboxylate Chemical compound COC(=O)C1=CC(Br)=CNC1=O TXZVFXMZHYRSDN-UHFFFAOYSA-N 0.000 description 1
USPNLIAOONIKNT-UHFFFAOYSA-N methyl 5-iodo-1,2-dihydropyridine-3-carboxylate Chemical compound COC(=O)C1=CC(I)=CNC1 USPNLIAOONIKNT-UHFFFAOYSA-N 0.000 description 1
LGUKGFMYVHZDEB-UHFFFAOYSA-N methyl 5-iodo-2-oxo-1h-pyridine-3-carboxylate Chemical compound COC(=O)C1=CC(I)=CNC1=O LGUKGFMYVHZDEB-UHFFFAOYSA-N 0.000 description 1
125000000896 monocarboxylic acid group Chemical group 0.000 description 1
PVNIIMVLHYAWGP-UHFFFAOYSA-M nicotinate Chemical compound [O-]C(=O)C1=CC=CN=C1 PVNIIMVLHYAWGP-UHFFFAOYSA-M 0.000 description 1
239000012434 nucleophilic reagent Substances 0.000 description 1
YJVFFLUZDVXJQI-UHFFFAOYSA-L palladium(ii) acetate Chemical compound [Pd+2].CC([O-])=O.CC([O-])=O YJVFFLUZDVXJQI-UHFFFAOYSA-L 0.000 description 1
RPGWZZNNEUHDAQ-UHFFFAOYSA-N phenylphosphine Chemical compound PC1=CC=CC=C1 RPGWZZNNEUHDAQ-UHFFFAOYSA-N 0.000 description 1
229910000073 phosphorus hydride Inorganic materials 0.000 description 1
230000000704 physical effect Effects 0.000 description 1
SIOXPEMLGUPBBT-UHFFFAOYSA-N picolinic acid Chemical compound OC(=O)C1=CC=CC=N1 SIOXPEMLGUPBBT-UHFFFAOYSA-N 0.000 description 1
239000002798 polar solvent Substances 0.000 description 1
229910000027 potassium carbonate Inorganic materials 0.000 description 1
239000002244 precipitate Substances 0.000 description 1
108090000765 processed proteins & peptides Proteins 0.000 description 1
125000001501 propionyl group Chemical group O=C([*])C([H])([H])C([H])([H])[H] 0.000 description 1
125000000714 pyrimidinyl group Chemical group 0.000 description 1
230000036647 reaction Effects 0.000 description 1
238000000926 separation method Methods 0.000 description 1
239000000377 silicon dioxide Substances 0.000 description 1
239000011734 sodium Substances 0.000 description 1
229910052708 sodium Inorganic materials 0.000 description 1
AKHNMLFCWUSKQB-UHFFFAOYSA-L sodium thiosulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=S AKHNMLFCWUSKQB-UHFFFAOYSA-L 0.000 description 1
235000019345 sodium thiosulphate Nutrition 0.000 description 1
125000000472 sulfonyl group Chemical group *S(*)(=O)=O 0.000 description 1
QAOWNCQODCNURD-UHFFFAOYSA-N sulfuric acid Substances OS(O)(=O)=O QAOWNCQODCNURD-UHFFFAOYSA-N 0.000 description 1
MVMJWFDNKYVKQT-SBFGLHDKSA-N taylor e Chemical compound C([C@H]1[C@@](C([C@@H](O)C2)=O)(C)CCCC1(C)C)[C@@H](O)C1=C[C@@H]2C(=C)C1=O MVMJWFDNKYVKQT-SBFGLHDKSA-N 0.000 description 1
125000000999 tert-butyl group Chemical group [H]C([H])([H])C(*)(C([H])([H])[H])C([H])([H])[H] 0.000 description 1
DZLFLBLQUQXARW-UHFFFAOYSA-N tetrabutylammonium Chemical compound CCCC[N+](CCCC)(CCCC)CCCC DZLFLBLQUQXARW-UHFFFAOYSA-N 0.000 description 1
229940124597 therapeutic agent Drugs 0.000 description 1
125000006000 trichloroethyl group Chemical group 0.000 description 1

Landscapes

Pyridine Compounds (AREA)
Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
Nitrogen Condensed Heterocyclic Rings (AREA)

CA000616047A 1986-10-20 1991-04-19 Procede pour la preparation de composes pyridyniques a anneaux condenses Expired - Fee Related CA1332169C (fr)

Priority Applications (1)

Application Number	Priority Date	Filing Date	Title
CA000616047A CA1332169C (fr)	1986-10-20	1991-04-19	Procede pour la preparation de composes pyridyniques a anneaux condenses

Applications Claiming Priority (4)

Application Number	Priority Date	Filing Date	Title
US922,511		1986-10-20
US06/922,511 US4818819A (en)	1986-10-20	1986-10-20	Process for the preparation of fused pyridine compounds
CA000549572A CA1301157C (fr)	1986-10-20	1987-10-19	Procede de preparation de composes a anneaux pyridine
CA000616047A CA1332169C (fr)	1986-10-20	1991-04-19	Procede pour la preparation de composes pyridyniques a anneaux condenses

Related Parent Applications (1)

Application Number	Title	Priority Date	Filing Date
CA000549572A Division CA1301157C (fr)	1986-10-20	1987-10-19	Procede de preparation de composes a anneaux pyridine

Publications (1)

Publication Number	Publication Date
CA1332169C true CA1332169C (fr)	1994-09-27

Family

ID=25671558

Family Applications (2)

Application Number	Title	Priority Date	Filing Date
CA000616047A Expired - Fee Related CA1332169C (fr)	1986-10-20	1991-04-19	Procede pour la preparation de composes pyridyniques a anneaux condenses
CA000616048A Expired - Fee Related CA1332170C (fr)	1986-10-20	1991-04-19	Procede pour la preparation de composes pyridyniques a anneaux condenses

Family Applications After (1)

Application Number	Title	Priority Date	Filing Date
CA000616048A Expired - Fee Related CA1332170C (fr)	1986-10-20	1991-04-19	Procede pour la preparation de composes pyridyniques a anneaux condenses

Country Status (1)

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CA (2)	CA1332169C (fr)

1991
- 1991-04-19 CA CA000616047A patent/CA1332169C/fr not_active Expired - Fee Related
- 1991-04-19 CA CA000616048A patent/CA1332170C/fr not_active Expired - Fee Related

Also Published As

Publication number	Publication date
CA1332170C (fr)	1994-09-27

Legal Events

Date	Code	Title	Description
2005-09-27	MKLA	Lapsed

Publication	Publication Date	Title
US4818819A (en)	1989-04-04	Process for the preparation of fused pyridine compounds
US4902796A (en)	1990-02-20	6-alkenyl and ethynyl derivatives of 2-amino-4-hydroxypyrido[2,3-d]pyrimidines
EP0204285B1 (fr)	1992-01-15	Composés imidazohétérocycliques, procédés pour leur préparation et compositions pharmaceutiques les contenant
EP0159264B1 (fr)	1991-07-24	Composés antiviraux
JPH05262769A (ja)	1993-10-12	医薬化合物
KR0159538B1 (ko)	1998-12-01	이미다조피리딘 유도체 및 그의 제조방법
Taylor et al.	1989	A facile route to" open chain" analogues of DDATHF
EP0314280B1 (fr)	1996-02-21	Procédé pour la préparation de composés condensés de pyridine
Matsumoto et al.	1984	Synthesis of fluorinated pyridines by the balz‐schiemann reaction. An alternative route to enoxacin, a new antibacterial pyridonecarboxylic acid
US4988813A (en)	1991-01-29	Process for the preparation of fused pyridine compounds
RU2002747C1 (ru)	1993-11-15	Способ получени производных глутаминовой кислоты или их фармацевтически приемлемых солей
CA1332169C (fr)	1994-09-27	Procede pour la preparation de composes pyridyniques a anneaux condenses
Lee et al.	1990	Synthesis of 2, 4-dialkoxy-6-(trifluoromethyl)-3, 5-pyridinedicarboxylates via a novel cyclocondensation of dialkyl 3-oxopentanedioates with trifluoroacetonitrile
Taylor et al.	1996	A Fischer-Indole Approach to Pyrrolo (2, 3-d) pyrimidines
JPH0635458B2 (ja)	1994-05-11	ピリドンカルボン酸誘導体、そのエステルおよびその塩
Lee et al.	1987	Antitumor agents. 86. Synthesis and cytotoxicity of. alpha.-methylene-. gamma.-lactone-bearing purines
KR970005301B1 (ko)	1997-04-15	2-치환 카르보닐이미다조[4,5-c]퀴놀린
US5254716A (en)	1993-10-19	Intermediates, and processes thereto, for the preparation of 5,6-dihydropyrrolo[2,3-d]pyrimidines
JPS62135458A (ja)	1987-06-18	新規キノロン化合物およびその製造法
Mataka et al.	1983	Preparation of hexa‐, penta‐and tetraphenyl‐2, 6‐and‐2, 7‐naphthyridines
CA1049017A (fr)	1979-02-20	Pyrrolo (3,4-b) pyridines et leurs methodes de preparation
JPH0586392B2 (fr)	1993-12-10
JP2709322B2 (ja)	1998-02-04	５―アセチル―２―ハロゲノピリミジン誘導体の製造法
KR890003358B1 (ko)	1989-09-19	새로운 티아졸 화합물의 제조공정
Gram et al.	1963	Potential Anticancer Agents. 1 LXXX. Alkylating Agents Related to Phenylalanine Mustard. 2 VI. Enantiomeric meta-Phenylalanine Mustards