GB2122615A - Preparation of fused carboxylic ring derivatives of pyridine - Google Patents
Preparation of fused carboxylic ring derivatives of pyridine Download PDFInfo
- Publication number
- GB2122615A GB2122615A GB08316272A GB8316272A GB2122615A GB 2122615 A GB2122615 A GB 2122615A GB 08316272 A GB08316272 A GB 08316272A GB 8316272 A GB8316272 A GB 8316272A GB 2122615 A GB2122615 A GB 2122615A
- Authority
- GB
- United Kingdom
- Prior art keywords
- compound
- formula
- group
- alkyl
- carbon atoms
- 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.)
- Granted
Links
- 238000002360 preparation method Methods 0.000 title description 3
- 150000003222 pyridines Chemical class 0.000 title description 3
- 150000001875 compounds Chemical class 0.000 claims abstract description 51
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 35
- 238000000034 method Methods 0.000 claims abstract description 31
- 125000004432 carbon atom Chemical group C* 0.000 claims abstract description 27
- -1 silyl compound Chemical class 0.000 claims abstract description 24
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 22
- 125000003118 aryl group Chemical group 0.000 claims abstract description 18
- 125000003710 aryl alkyl group Chemical group 0.000 claims abstract description 13
- 125000004104 aryloxy group Chemical group 0.000 claims abstract description 13
- 125000000753 cycloalkyl group Chemical group 0.000 claims abstract description 10
- 229910052744 lithium Inorganic materials 0.000 claims abstract description 10
- ZAMOUSCENKQFHK-UHFFFAOYSA-N Chlorine atom Chemical compound [Cl] ZAMOUSCENKQFHK-UHFFFAOYSA-N 0.000 claims abstract description 9
- 125000004414 alkyl thio group Chemical group 0.000 claims abstract description 9
- 239000000460 chlorine Substances 0.000 claims abstract description 9
- 229910052801 chlorine Inorganic materials 0.000 claims abstract description 9
- 229910052708 sodium Inorganic materials 0.000 claims abstract description 9
- 239000011734 sodium Substances 0.000 claims abstract description 9
- WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical compound [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 claims abstract description 8
- DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical group 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 claims abstract description 8
- GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 claims abstract description 8
- 229910052794 bromium Inorganic materials 0.000 claims abstract description 8
- 239000001257 hydrogen Substances 0.000 claims abstract description 8
- 229910052739 hydrogen Inorganic materials 0.000 claims abstract description 8
- 150000002825 nitriles Chemical class 0.000 claims abstract description 8
- 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 abstract description 8
- WHXSMMKQMYFTQS-UHFFFAOYSA-N Lithium Chemical compound [Li] WHXSMMKQMYFTQS-UHFFFAOYSA-N 0.000 claims abstract description 7
- 239000002253 acid Substances 0.000 claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 claims abstract description 7
- 229910052700 potassium Inorganic materials 0.000 claims abstract description 7
- 125000001424 substituent group Chemical group 0.000 claims abstract description 7
- HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 claims abstract description 6
- ZLMJMSJWJFRBEC-UHFFFAOYSA-N Potassium Chemical compound [K] ZLMJMSJWJFRBEC-UHFFFAOYSA-N 0.000 claims abstract description 6
- 239000011591 potassium Substances 0.000 claims abstract description 6
- 150000003839 salts Chemical class 0.000 claims abstract description 6
- 125000000000 cycloalkoxy group Chemical group 0.000 claims abstract description 5
- PNDPGZBMCMUPRI-UHFFFAOYSA-N iodine Chemical compound II PNDPGZBMCMUPRI-UHFFFAOYSA-N 0.000 claims abstract description 5
- 229910052757 nitrogen Inorganic materials 0.000 claims abstract description 5
- 150000003254 radicals Chemical class 0.000 claims abstract description 5
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical group [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims abstract description 4
- 239000005864 Sulphur Chemical group 0.000 claims abstract description 4
- 238000006136 alcoholysis reaction Methods 0.000 claims abstract description 4
- 125000005110 aryl thio group Chemical group 0.000 claims abstract description 4
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical group [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims abstract description 4
- 125000003917 carbamoyl group Chemical group [H]N([H])C(*)=O 0.000 claims abstract description 4
- 125000005366 cycloalkylthio group Chemical group 0.000 claims abstract description 4
- 230000007062 hydrolysis Effects 0.000 claims abstract description 4
- 238000006460 hydrolysis reaction Methods 0.000 claims abstract description 4
- 239000001301 oxygen Substances 0.000 claims abstract description 4
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 4
- UFHFLCQGNIYNRP-UHFFFAOYSA-N Hydrogen Chemical compound [H][H] UFHFLCQGNIYNRP-UHFFFAOYSA-N 0.000 claims abstract description 3
- 125000004659 aryl alkyl thio group Chemical group 0.000 claims abstract description 3
- 150000005840 aryl radicals Chemical class 0.000 claims abstract description 3
- 125000004433 nitrogen atom Chemical group N* 0.000 claims abstract description 3
- 229920006395 saturated elastomer Polymers 0.000 claims abstract description 3
- 125000000623 heterocyclic group Chemical group 0.000 claims abstract 2
- 125000001183 hydrocarbyl group Chemical group 0.000 claims abstract 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical group C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 claims description 26
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 claims description 17
- 239000002904 solvent Substances 0.000 claims description 16
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 claims description 13
- 238000006243 chemical reaction Methods 0.000 claims description 11
- 150000001408 amides Chemical class 0.000 claims description 10
- 229910052751 metal Inorganic materials 0.000 claims description 9
- 239000002184 metal Substances 0.000 claims description 9
- WDQDMOPZMLEJKT-UHFFFAOYSA-N isothiocyanatosilane Chemical compound [SiH3]N=C=S WDQDMOPZMLEJKT-UHFFFAOYSA-N 0.000 claims description 6
- 238000007429 general method Methods 0.000 claims description 4
- ZMZDMBWJUHKJPS-UHFFFAOYSA-M Thiocyanate anion Chemical compound [S-]C#N ZMZDMBWJUHKJPS-UHFFFAOYSA-M 0.000 claims description 3
- XLJMAIOERFSOGZ-UHFFFAOYSA-M cyanate Chemical compound [O-]C#N XLJMAIOERFSOGZ-UHFFFAOYSA-M 0.000 claims description 3
- 150000004292 cyclic ethers Chemical group 0.000 claims description 3
- 125000004663 dialkyl amino group Chemical group 0.000 claims description 3
- 125000004435 hydrogen atom Chemical group [H]* 0.000 claims description 3
- ZMZDMBWJUHKJPS-UHFFFAOYSA-N hydrogen thiocyanate Natural products SC#N ZMZDMBWJUHKJPS-UHFFFAOYSA-N 0.000 claims description 3
- 238000011065 in-situ storage Methods 0.000 claims description 3
- 239000007858 starting material Substances 0.000 claims description 3
- HBVRTKGMXUJGSA-UHFFFAOYSA-N (2,6-ditert-butyl-4-methylphenoxy)-isothiocyanato-dimethylsilane Chemical compound CC1=CC(C(C)(C)C)=C(O[Si](C)(C)N=C=S)C(C(C)(C)C)=C1 HBVRTKGMXUJGSA-UHFFFAOYSA-N 0.000 claims description 2
- RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 2
- 150000002431 hydrogen Chemical class 0.000 claims description 2
- 150000002540 isothiocyanates Chemical class 0.000 claims description 2
- BOIHJZYMSZBOMW-UHFFFAOYSA-N lithium;tert-butyl(1-phenylpentyl)azanide Chemical group [Li+].CCCCC([N-]C(C)(C)C)C1=CC=CC=C1 BOIHJZYMSZBOMW-UHFFFAOYSA-N 0.000 claims description 2
- HSZJNJLFBWBGEA-UHFFFAOYSA-N n-[bis(dimethylamino)-isothiocyanatosilyl]-n-methylmethanamine Chemical compound CN(C)[Si](N(C)C)(N(C)C)N=C=S HSZJNJLFBWBGEA-UHFFFAOYSA-N 0.000 claims description 2
- 125000002572 propoxy group Chemical group [*]OC([H])([H])C(C([H])([H])[H])([H])[H] 0.000 claims description 2
- GNKSAARCKYTMMD-UHFFFAOYSA-N isothiocyanato-dimethyl-propan-2-yloxysilane Chemical compound CC(C)O[Si](C)(C)N=C=S GNKSAARCKYTMMD-UHFFFAOYSA-N 0.000 claims 2
- 238000002474 experimental method Methods 0.000 claims 1
- OFYZZNNWQRYKHA-UHFFFAOYSA-N isothiocyanato-dimethoxy-methylsilane Chemical compound CO[Si](C)(OC)N=C=S OFYZZNNWQRYKHA-UHFFFAOYSA-N 0.000 claims 1
- ISWWWCYIMPOYHB-UHFFFAOYSA-N isothiocyanato-methoxy-dimethylsilane Chemical compound CO[Si](C)(C)N=C=S ISWWWCYIMPOYHB-UHFFFAOYSA-N 0.000 claims 1
- 238000012986 modification Methods 0.000 claims 1
- 230000004048 modification Effects 0.000 claims 1
- 125000000147 tetrahydroquinolinyl group Chemical class N1(CCCC2=CC=CC=C12)* 0.000 claims 1
- 150000003556 thioamides Chemical class 0.000 abstract description 4
- 230000000767 anti-ulcer Effects 0.000 abstract description 3
- 239000003699 antiulcer agent Substances 0.000 abstract description 2
- 239000002731 stomach secretion inhibitor Substances 0.000 abstract 1
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 21
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 9
- DLEDOFVPSDKWEF-UHFFFAOYSA-N lithium butane Chemical compound [Li+].CCC[CH2-] DLEDOFVPSDKWEF-UHFFFAOYSA-N 0.000 description 9
- MZRVEZGGRBJDDB-UHFFFAOYSA-N n-Butyllithium Substances [Li]CCCC MZRVEZGGRBJDDB-UHFFFAOYSA-N 0.000 description 9
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 6
- 239000000203 mixture Substances 0.000 description 6
- 239000000047 product Substances 0.000 description 6
- IJGRMHOSHXDMSA-UHFFFAOYSA-N Atomic nitrogen Chemical compound N#N IJGRMHOSHXDMSA-UHFFFAOYSA-N 0.000 description 4
- SOIFLUNRINLCBN-UHFFFAOYSA-N ammonium thiocyanate Chemical compound [NH4+].[S-]C#N SOIFLUNRINLCBN-UHFFFAOYSA-N 0.000 description 4
- 239000003153 chemical reaction reagent Substances 0.000 description 4
- 239000000543 intermediate Substances 0.000 description 4
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 4
- 125000001181 organosilyl group Chemical group [SiH3]* 0.000 description 4
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 3
- ZMANZCXQSJIPKH-UHFFFAOYSA-N Triethylamine Chemical compound CCN(CC)CC ZMANZCXQSJIPKH-UHFFFAOYSA-N 0.000 description 3
- KOPOQZFJUQMUML-UHFFFAOYSA-N chlorosilane Chemical compound Cl[SiH3] KOPOQZFJUQMUML-UHFFFAOYSA-N 0.000 description 3
- 150000002170 ethers Chemical class 0.000 description 3
- 150000002430 hydrocarbons 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
- NLXLAEXVIDQMFP-UHFFFAOYSA-N Ammonia chloride Chemical compound [NH4+].[Cl-] NLXLAEXVIDQMFP-UHFFFAOYSA-N 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 2
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- CSNNHWWHGAXBCP-UHFFFAOYSA-L Magnesium sulfate Chemical compound [Mg+2].[O-][S+2]([O-])([O-])[O-] CSNNHWWHGAXBCP-UHFFFAOYSA-L 0.000 description 2
- NQRYJNQNLNOLGT-UHFFFAOYSA-N Piperidine Chemical compound C1CCNCC1 NQRYJNQNLNOLGT-UHFFFAOYSA-N 0.000 description 2
- CDBYLPFSWZWCQE-UHFFFAOYSA-L Sodium Carbonate Chemical compound [Na+].[Na+].[O-]C([O-])=O CDBYLPFSWZWCQE-UHFFFAOYSA-L 0.000 description 2
- 230000001262 anti-secretory effect Effects 0.000 description 2
- 125000002837 carbocyclic group Chemical group 0.000 description 2
- 229930195733 hydrocarbon Natural products 0.000 description 2
- 239000012429 reaction media Substances 0.000 description 2
- 238000003756 stirring Methods 0.000 description 2
- QFLWZFQWSBQYPS-AWRAUJHKSA-N (3S)-3-[[(2S)-2-[[(2S)-2-[5-[(3aS,6aR)-2-oxo-1,3,3a,4,6,6a-hexahydrothieno[3,4-d]imidazol-4-yl]pentanoylamino]-3-methylbutanoyl]amino]-3-(4-hydroxyphenyl)propanoyl]amino]-4-[1-bis(4-chlorophenoxy)phosphorylbutylamino]-4-oxobutanoic acid Chemical compound CCCC(NC(=O)[C@H](CC(O)=O)NC(=O)[C@H](Cc1ccc(O)cc1)NC(=O)[C@@H](NC(=O)CCCCC1SC[C@@H]2NC(=O)N[C@H]12)C(C)C)P(=O)(Oc1ccc(Cl)cc1)Oc1ccc(Cl)cc1 QFLWZFQWSBQYPS-AWRAUJHKSA-N 0.000 description 1
- YXHXNUQDELNVHY-UHFFFAOYSA-N 1,2,3,4-tetrahydroquinoline-8-carbothioamide Chemical class C1CCNC2=C1C=CC=C2C(=S)N YXHXNUQDELNVHY-UHFFFAOYSA-N 0.000 description 1
- RKMGAJGJIURJSJ-UHFFFAOYSA-N 2,2,6,6-tetramethylpiperidine Chemical compound CC1(C)CCCC(C)(C)N1 RKMGAJGJIURJSJ-UHFFFAOYSA-N 0.000 description 1
- MUZLJLSOGBHBDC-UHFFFAOYSA-N 5,6,7,8-tetrahydroquinoline-8-carbothioamide Chemical compound C1=CN=C2C(C(=S)N)CCCC2=C1 MUZLJLSOGBHBDC-UHFFFAOYSA-N 0.000 description 1
- NLZUEZXRPGMBCV-UHFFFAOYSA-N Butylhydroxytoluene Chemical compound CC1=CC(C(C)(C)C)=C(O)C(C(C)(C)C)=C1 NLZUEZXRPGMBCV-UHFFFAOYSA-N 0.000 description 1
- FSFVNJYOHZTIBV-UHFFFAOYSA-N C1=CN=C2C([Li])CCCC2=C1 Chemical compound C1=CN=C2C([Li])CCCC2=C1 FSFVNJYOHZTIBV-UHFFFAOYSA-N 0.000 description 1
- XDTMQSROBMDMFD-UHFFFAOYSA-N Cyclohexane Chemical compound C1CCCCC1 XDTMQSROBMDMFD-UHFFFAOYSA-N 0.000 description 1
- XBPCUCUWBYBCDP-UHFFFAOYSA-N Dicyclohexylamine Chemical compound C1CCCCC1NC1CCCCC1 XBPCUCUWBYBCDP-UHFFFAOYSA-N 0.000 description 1
- HQABUPZFAYXKJW-UHFFFAOYSA-N N-butylamine Natural products CCCCN HQABUPZFAYXKJW-UHFFFAOYSA-N 0.000 description 1
- KEAYESYHFKHZAL-UHFFFAOYSA-N Sodium Chemical compound [Na] KEAYESYHFKHZAL-UHFFFAOYSA-N 0.000 description 1
- 125000005119 alkyl cycloalkyl group Chemical group 0.000 description 1
- 235000019270 ammonium chloride Nutrition 0.000 description 1
- 239000007864 aqueous solution Substances 0.000 description 1
- 125000002102 aryl alkyloxo group Chemical group 0.000 description 1
- 150000003940 butylamines Chemical group 0.000 description 1
- 150000003857 carboxamides Chemical class 0.000 description 1
- DDDJKVFRSZFKPM-UHFFFAOYSA-N chloro-(2,6-ditert-butyl-4-methylphenoxy)-dimethylsilane Chemical compound CC1=CC(C(C)(C)C)=C(O[Si](C)(C)Cl)C(C(C)(C)C)=C1 DDDJKVFRSZFKPM-UHFFFAOYSA-N 0.000 description 1
- 239000002026 chloroform extract Substances 0.000 description 1
- 150000001923 cyclic compounds Chemical class 0.000 description 1
- 125000001995 cyclobutyl group Chemical group [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000000113 cyclohexyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C([H])([H])C1([H])[H] 0.000 description 1
- 125000001511 cyclopentyl group Chemical group [H]C1([H])C([H])([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 description 1
- 125000005265 dialkylamine group Chemical group 0.000 description 1
- HPNMFZURTQLUMO-UHFFFAOYSA-N diethylamine Chemical compound CCNCC HPNMFZURTQLUMO-UHFFFAOYSA-N 0.000 description 1
- UAOMVDZJSHZZME-UHFFFAOYSA-N diisopropylamine Chemical compound CC(C)NC(C)C UAOMVDZJSHZZME-UHFFFAOYSA-N 0.000 description 1
- 125000002147 dimethylamino group Chemical group [H]C([H])([H])N(*)C([H])([H])[H] 0.000 description 1
- LIKFHECYJZWXFJ-UHFFFAOYSA-N dimethyldichlorosilane Chemical compound C[Si](C)(Cl)Cl LIKFHECYJZWXFJ-UHFFFAOYSA-N 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 239000000706 filtrate Substances 0.000 description 1
- 238000001914 filtration Methods 0.000 description 1
- 239000012442 inert solvent Substances 0.000 description 1
- 239000012948 isocyanate Substances 0.000 description 1
- 150000002513 isocyanates Chemical class 0.000 description 1
- 125000001449 isopropyl group Chemical group [H]C([H])([H])C([H])(*)C([H])([H])[H] 0.000 description 1
- AFRJJFRNGGLMDW-UHFFFAOYSA-N lithium amide Chemical compound [Li+].[NH2-] AFRJJFRNGGLMDW-UHFFFAOYSA-N 0.000 description 1
- 239000011777 magnesium Substances 0.000 description 1
- 229910052749 magnesium Inorganic materials 0.000 description 1
- 229910052943 magnesium sulfate Inorganic materials 0.000 description 1
- 235000019341 magnesium sulphate Nutrition 0.000 description 1
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 1
- 125000004108 n-butyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- GMTCPFCMAHMEMT-UHFFFAOYSA-N n-decyldecan-1-amine Chemical compound CCCCCCCCCCNCCCCCCCCCC GMTCPFCMAHMEMT-UHFFFAOYSA-N 0.000 description 1
- UYYCVBASZNFFRX-UHFFFAOYSA-N n-propan-2-ylcyclohexanamine Chemical compound CC(C)NC1CCCCC1 UYYCVBASZNFFRX-UHFFFAOYSA-N 0.000 description 1
- 125000004123 n-propyl group Chemical group [H]C([H])([H])C([H])([H])C([H])([H])* 0.000 description 1
- KZOPSPQZLMCNPF-UHFFFAOYSA-N n-tert-butyl-2-methylbutan-2-amine Chemical compound CCC(C)(C)NC(C)(C)C KZOPSPQZLMCNPF-UHFFFAOYSA-N 0.000 description 1
- 239000012454 non-polar solvent Substances 0.000 description 1
- 150000002902 organometallic compounds Chemical class 0.000 description 1
- DOIRQSBPFJWKBE-UHFFFAOYSA-N phthalic acid di-n-butyl ester Natural products CCCCOC(=O)C1=CC=CC=C1C(=O)OCCCC DOIRQSBPFJWKBE-UHFFFAOYSA-N 0.000 description 1
- 125000003386 piperidinyl group Chemical group 0.000 description 1
- 150000003112 potassium compounds Chemical class 0.000 description 1
- 125000002924 primary amino group Chemical group [H]N([H])* 0.000 description 1
- 125000000719 pyrrolidinyl group Chemical group 0.000 description 1
- 238000001953 recrystallisation Methods 0.000 description 1
- 238000010992 reflux Methods 0.000 description 1
- 239000004576 sand Substances 0.000 description 1
- 150000003335 secondary amines Chemical class 0.000 description 1
- 235000017550 sodium carbonate Nutrition 0.000 description 1
- 229910000029 sodium carbonate Inorganic materials 0.000 description 1
- 239000000243 solution Substances 0.000 description 1
- 239000000725 suspension Substances 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
- 238000010998 test method Methods 0.000 description 1
- 150000003530 tetrahydroquinolines Chemical class 0.000 description 1
- 239000012485 toluene extract Substances 0.000 description 1
- 230000001052 transient effect Effects 0.000 description 1
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 1
Classifications
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D215/00—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems
- C07D215/02—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom
- C07D215/16—Heterocyclic compounds containing quinoline or hydrogenated quinoline ring systems having no bond between the ring nitrogen atom and a non-ring member or having only hydrogen atoms or carbon atoms directly attached to the ring nitrogen atom with hetero atoms or with carbon atoms having three bonds to hetero atoms with at the most one bond to halogen, e.g. ester or nitrile radicals, directly attached to ring carbon atoms
- C07D215/48—Carbon atoms having three bonds to hetero atoms with at the most one bond to halogen
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/025—Silicon compounds without C-silicon linkages
-
- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07F—ACYCLIC, CARBOCYCLIC OR HETEROCYCLIC COMPOUNDS CONTAINING ELEMENTS OTHER THAN CARBON, HYDROGEN, HALOGEN, OXYGEN, NITROGEN, SULFUR, SELENIUM OR TELLURIUM
- C07F7/00—Compounds containing elements of Groups 4 or 14 of the Periodic Table
- C07F7/02—Silicon compounds
- C07F7/08—Compounds having one or more C—Si linkages
- C07F7/18—Compounds having one or more C—Si linkages as well as one or more C—O—Si linkages
- C07F7/1804—Compounds having Si-O-C linkages
Landscapes
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
Abstract
A process for preparing compounds of formula I <IMAGE> or acid addition salts thereof, wherein R<1>, R<2>, R<3>, R<4> and R<5> are the same or different and represent hydrogen or alkyl, cycloalkyl, aralkyl, or aryl radicals, any of which radicals may be substituted, or R<1> and R<2> taken together, or R<2> and R<3> taken together form a 5, 6, or 7 membered ring which may be saturated or unsaturated and substituted or unsubstituted, and when R<1> and R<2> form a ring, the ring has the same number of carbon atoms as the ring carrying X, R<4> and R<5> may also represent alkoxy, n is 1, 2 or 3 and X is CN, CONH2, or CSNH2 which process comprises treating a compound of formula II <IMAGE> wherein R<1>, R<2>, R<3>, R<4>, R<5> and n are as defined in connection with formula I, and M or is sodium, potassium, lithium, or MgHal, where Hal is chlorine, bromine or iodine, with a silyl compound of formula III, R<a>xSi(NCY)4-x wherein R<a> is selected from electron donating substituents including alkoxy, cycloalkoxy, aralkoxy, aryloxy, the group R<b>R<c>N-wherein R<b> and R<c> are selected from alkyl, cycloalkyl, aryl and aralkyl or R<b> and R<c> may be joined to form a heterocyclic ring with the nitrogen atom, alkylthio, cycloalkylthio, aralkylthio, arylthio and hydrocarbon substituents selected from alkyl, cycloalkyl, aralkyl or aryl, at least one group R<a> being an electron donating substituent, Y is oxygen or sulphur, x has a value from 1 to 3, then subjecting the product to hydrolysis or alcoholysis, with the proviso that when a compound of formula I in which X is CN is desired the molar ratio of compound R<a>xSi(NCY)4-x to compound II is at least 2:1 and x is 3 and Y is S and if desired isolating the product as an acid addition salt. The nitriles and thioamides are anti-ulcer and/or anti-secretory agents. Some compounds of the formula III are claimed together with compounds of the formulae VI and VII <IMAGE>
Description
SPECIFICATION
Preparation of fused carbocyclic ring derivatives of pyridine
The invention relates to a new process for preparing fused carbocyclic ring derivatives of pyridine.
In our United Kingdom Patent Specification No. 1463666 we described a process for preparing tetrahydroquinoline-8-thiocarboxamides, nitriles and carboxamides and related compounds by treating a corresponding sodio, lithio, potassio or magnesium halide derivative with a silyl compound of formula RXSi(NCY)4-x wherein R is alkyl, aryl or aralky, Y is oxygen or sulphur and x has a value from 0 to 3 and subjecting the product to hydrolysis or alcoholysis. The reaction is conducted under anhydrous conditions preferably in an inert solvent for example a hydrocarbon solvent such as benzene, toluene or n-hexane. It is also stated in the patent specification that ethers, including cyclic ethers such as tetrahydrofuran should be avoided.
We have now surprisingly found that ethers can be used as solvents if the silyl reagent is modified to contain an alkoxy group or other electron donating substituent. Our new process an also be used to prepare compounds related to those described in Patent Specification 1463666. The new reagents can also be used in the same solvents described in UK Specification 1463666.
Accordingly this invention provides in one aspect, a process for preparing compounds of formula I
or acid addition salts thereof, wherein R', R2, R3, R4 and R5 are the same or different and represent hydrogen or alkyl cycloalkyl, aralkyl, or aryl radicals, any of which radicals may be substituted, or R1 and R2 taken together, or R2 and R3 taken together form a 5, 6, or 7 membered ring which may be saturated or unsaturated and substituted or unsubstituted, and when R1 and R2 form a ring, the ring has the same number of carbon atoms as the ring carrying X, R4 and R5 may also represent alkoxy, n is 1,2 or 3 and Xis CN, CONH2, or CSNH2which process comprises treating a compound of formula II
wherein R1, R2, R3, R4, R5 and n are as defined in connection with formula i, and M is sodium, potassum, lithium, or MgHal, where Hal is chlorine, bromine or iodine, with a silyl compound of formula Ill, RXSi(NCY)4-x wherein Ra is selected from electron donating substituents including alkoxy, cycloalkoxy, aralkoxy, aryloxy, the group RbRCN-wherein Rb and RC are selected from alkyl, cycloalkyl, aryl and aralkyl or
Rb and Rc may be joined to form a hetercyclic ring with the nitrogen atom (eg., a piperidinyl or pyrrolidinyl ring, which may be substituted eg., by alkyl), alkylthio, cycloalkylthio, aralkylthio, arylthio and hydrocarbon substituents selected from alkyl, cycloalkyl, aralkyl or aryl, at least one group Ra being an electron donating substituent, Y is oxygen or sulphur, x has a value from 1 to 3, then subjecting the product to hydrolysis or alcoholysis, with the proviso that when a compound of formula I in which Xis CN is desired the molar ratio of compound RXSi(NCY)4-x to compound II is at least 2:1 and xis 3 and Y is Sand if desired isolating the product as an acid addition salt.
The compounds of formula land Il are, in general, known compounds which are described in UK Patent Specifications 1463666, 1432378, 1463668, 1465651 and 1495993 or are analogous to compounds described therein. Compounds of formula Il in which M is MgHal are also described in UK Patent 1463665 or are analogous to compounds described therein. The compounds offormula I in which Xis CSNH2 are anti-ulcer agents which display anti-ulcer and/or anti-secretory activity in standard test procedures. The nitriles of formula I where X is CN are intermediates for the corresponding thioamides and usually also display anti-ulcer and/or anti-secretory activity.The amides of formula I in which Xis CONH2 are intermediates for the corresponding nitriles and thioamides.
In general the preferred reaction medium for the process of the present invention comprises an ether solvent eg., a dialkyl ethere, wherein the alkyl group has from 1 to 6 carbon atoms, eg., diethyl ether or a cyclic ether such as tetrahydrofuran or dioxan. Other reaction media which may be used are hydrocarbon solvents such as benzene, toluene or n-hexane, or mixtures of two or more of the above mentioned solvents.
Preferably at least one electron donating group Ra is alkoxy of 1-10 carbon atoms, cycloalkoxy of 4-8 carbon atoms, aryloxy, aralkoxy of 7-12 carbon atoms or di(C1-Cs alkyl)amino. Good results have been obtained with a silyl compound of formula R3SiNCY wherein one group Ra is lower alkoxy or aryloxy and these other two are lower alkyl eg., methoxy dimethylsilyl isothiocyanate isopropoxydimethylsilyl.
sothiocyanate 2,6-di-t-butyl-4-methyl phenoxydimethylsilyl isothiocyanate.
However two or all three of the Ra groups may be alkoxy eg., trimethoxy or triethoxy, or dialkylamino eg dimethylamino. Branched chain alkoxy or arloxy groups are preferred. A particularly useful compound Ill is tri(dimethylamino)silyl isothiocyanate. Ra may have from 1-10 carbon atoms when alkyl or alkylthio.
When any of R1, R2, R3, R4, R5, Ra, Rb or Re is an alkyl radical it is preferred that this is a lower alkyl radical of 1 to 6 carbon atoms which may have a straight or branched chain eg., methyl, ethyl, n-and iso-propyl and n-, and t-butyl. When R4, R5, or Ra is an alkoxy radical it is preferred that the radical is lower alkoxy in which the alkyl portion has 1 to 6 carbon atoms and is as defined above, for an alkyl radical. Similarly when Ra is an alkylthio group the alkyl portion is as defined for an alkyl group.
When any of R1, R2, R3, R4, R5, Ra, Rb or Rc is a cycloalkyl radical such radicals having from 4 to 6 carbon atoms are preferred ie., cyclobutyl, cyclopentyl or cyclohexyl. If Ra is cycloalkoxy or cycloalkylthio the cycloalkyl portion of this group preferably has from 4 to 8 carbon atoms but may be as just described for a cycloalkyl group.
An aralkyl group may be an arylalkyl group in which the alkyl portion is as described herein for an alkyl group. Preferred aralkyl groups are those having from 7-12 carbon atoms.
An aralkyloxy group may be such a group in which the aralkyl portion is as just described for an aralkyl group. The aryl portion is preferably phenyl.
When any of R1, R2, R3, R4, R5, Ra, Rb or Re is an aryl group it is preferably phenyl or substituted phenyl (substituted by eg., alkyl, alkoxy, ortrifluoromethyl). Similarly an aryloxy or arylthio group may be such a group in which the aryl portion is as defined for an aryl group, 2,6-disubstituted phenyl being a preferred group.
Apart from the question of solvent, already discussed above, the reaction may be carried out as described generally in UK Patent Specification No. 1463666. Conveniently the starting material of formula II is prepared in situ by reaction of a compound of formula II, wherein M is hydrogen with a suitable organometallic compound such as an alkyl, aryl or aralkyl lithium, sodium or potassium compound as described in UK
Patent Specification 1432378 or using the improvement described in UK Patent Specification 1463666, wherein a metal amide is reacted with a compound of formula II wherein M is hydrogen.The metal amide may be formed in situ and may be any of those described in UK Patent Specification 1463666 viz. an amide derived from a secondary amine such as a dialkylamine eg., diethylamine, di-isopropylamine, ditertiary butylamine, di-n-decylamine, dicyclohexylamine, N-t-amyl N-t-butylamine, N-isopropyl-N-cyclohexylamine, or N(1 -ethylcyclohexyl)-1 1 ,3,3,-tetramethylbutylamine or a cyclic compound eg., piperidine or 2,2,6,6, tetramethylpiperidine. Alternatively any of the metal amides described in our co-pending UK Application 8306456 filed 9th March 1983 may be used. These metal amides have the formula IV
wherein R14 is a straight or branched chain alkyl group of 1 to 6 carbon atoms or an aryl group, R'1 is hydrogen, aryl or a tertiary alkyl group of 4-6 carbon atoms, R12 is aryl or a tertiary alkyl group of 4-6 carbon atoms, R'3 is a branched chain alkyl of 3 to 6 carbon atoms; X1 is lithium, sodium or potassium. These metal amides are conveniently prepared by a novel process described in UK Application 8306456 namely reacting a compound of formula V.
wherein R11, R12 and R13 are as defined above with a metal alkyl MR14 where R14 is as defined above and M is lithium, sodium or potassium, in an inert non-polar solvent to obtain a compound of formula IV.
A particularly preferred compound of formula IV is lithium N-t-butyl-N-(1-phenylpentyl)amide.
The starting compounds of formula II, wherein Xis MgHal may be prepared by the general method described in UK Patent Specification 1463665. However, in our UK Patent Specification 1463666 it is said that the ether solvent has to be removed and the reaction with the silyl compound conducted in a different solvent. Since the process of the present invention can be conducted in ethers it is not usually necessary to remove the ether when the MgHal compound II has been prepared in an ether solvent.
The silyl compounds of formula Ill which are used in the process of the present invention may be prepared by reacting a thiocyanate, such as ammonium thiocyanate, or a cyanate, with a silyl halide, RxSiHal4~x eg., R3a SiHal where Ra is as defined above and Hal is chlorine or bromine.
Some of the silyl isothiocyanates or isocyanates of formula III are novel compounds and the novel compounds are included in the invention. They have formula Illa.
RXaSi(NCY)4-x Illa wherein Ra, x and Y are as defined in connection with formula III with the provisos that (i) when xis 3 and all three Ra groups are the same alkoxy then the alkoxy group has at least 3 carbon
atoms; (ii) when Ra is alkoxy and xis 1 then Ra is other than propoxy; (iii) when one or more Ra are alkylthio and the others (if any) are alkyl then the alkylthio group has at
least 2 carbon atoms;; (iv) when Ra is aryloxy and xis 3 then at least one group Ra is other than aryloxy
Novel compounds of the invention include compounds of formula Illa, wherein one or two groups Ra are alkoxy or aryloxy and another group Ra is alkyl and x is 3 eg., Me2(OMe)SiNCS
Me2(OiPr)SiNCS Me(OMe)2SiNCS 2,6,di-t-butyl-4-methylphenoxy (Me)2SiNCS and where one or more groups Ra are dialkylamino eg., (MeN2)3SiNCS.
The compounds of formula Ill (including the novel compounds of formula Illa) may be prepared by reacting a silylhalide RxSi(Hal)4~x, wherein Hal is chlorine, bromine or iodine, preferably chlorine, [Ra and x being as defined above] with a thiocyanate eg., ammonium thiocyanate, or a cyanate. Methods of preparing the novel compounds of formula Ill are included in the invention.
When it is desired to prepare nitriles of formula I by the above reaction instead of using 2 or more moles of compound RXaSi(NCY)4-x to compound 11 the reaction may be carried out by reacting 1 mol of compound RXSi(NCY)4-x with compound II wherein M is Na, K or Li followed by addition of 1 or more mols of RXSiHal4-X wherein Ra and x are as defined previously and Hal is chlorine or bromine, Ra and x in this reagent need not be the same as in the reagent RXaSi(NCY)4-xB This process for preparing nitriles is also included in the invention.
The silylhalides are known or may be prepared by methods known for analogous compounds.
The invention also includes further novel compounds offormula VI
wherein R1, R2, R3, R4, R5, Ra, n, x, Y and M are as defined above. These novel compounds are the products of the first stage of reaction between the compound of formula II and the compound of formula Ill. This compound of formula VI is converted into the desired compound of formula I via an intermediate of formula VII, which may be transient,
wherein R1, R2, R3, R4, R5, Ra, n, x and Y are as defined above.
The intermediates of formula VII are also included in the invention.
The following Examples illustrate the invention.
EXAMPLE 1
Preparation of silyl isothiocyanates
General Method
Ammonium thiocyanate (1.1 molar equivalents) in cyclohexane (100 ml) was refluxed with stirring under a
Dean-Stark apparatus until water had been removed. The suspension was cooled and treated with silyl chloride (50g) and the mixture was heated at reflux with stirring until the reaction was complete (usually 24 hour) Precipitated ammonium chloride was removed by filtration and the product purified by distiliation.In this mannerwere prepared the following:
Silyl chloride Silylisothiocyanate bp/mm Yield a) Me2(OMe)SiCI Me2(OMe)SiNCS 148 C/760 68% b) Me2(OiPr)SiCI Me2(OiPr)SiNCS 68"C/15 79% c) Me(OMe)2SiCI Me(OMe)2SiNCS 58"C/15 66% d) (OEt)3SiCI (OEt)3SiNCS 98"C/15 95% e) (Me2N)3SiCI (Me2N)3SiNCS 140"C/15 15%
EXAMPLE 2
Reaction of silyliso thiocyanates with tetrahydroquinolines
General Method
A 5,6,7,84etrahydroquinoline (0.01 mole) in the solvent indicated (approx. 15 ml) at OOC under nitrogen was treated with an alkyl lithium or a lithium amide (0.01 mole).To this solution of the 5,6,7,8-tetrahydro-8lithioquinoline was added, at around 0 C under nitrogen, the silyl isothiocyanate (0.01 mole) and the mixture was stirred 15 minutes. H2O(10ml) and 2N HCI (15ml) were added and the acid layer was separated and washed with ethyl acetate. The aqueous solution was basified (Na2CO3) and extracted with chloroform. The chloroform extracts were dried (MgSO4) and evaporated to give the 5,6,7,8-tetrahydroquinoline-8thiocarboxamide. In this manner the thioamides in the table were prepared.
Silyl Yield Expt. R15 derivatives Solvent Base (n.m.r) (a) 3-Me Me2Si(OMe)NCS THF n-BuLi 5% (b) 3-Me Me2Si(OiPr)NCS THF n-BuLi 30-35% (c) 3-Me Me2Si(OiPr)NCS toluene n-BuLi 15% (d) 4-Me Me2Si(OiPr)NCS toluene n-BuLi 5% (e) 4-Me Me2Si(OiPr)NCS THF n-BuLi 10% Ph (f) 4-Me Me2Si(OiPr)NCS toluene XN + 20% Bu L. (g) 4-Me Me2Si(OiPr)NCS THF II 25% (h) 3-Me (EtO)3SiNCS THF n-BuLi 10% (i) 3-Me Me(OMe)2SiNCS THF n-BuLi 10% (j) 3-Me (Me2N)3SiNCS THF n-BuLi 40% But (k) 3-Me G/ G THF n-BuLi 50% Me2 But
No product was obtained when the above reactions were carried out using Me3SiNCS in tetrahydrofuran (THF) instead of the named silyl derivative.
EXAMPLE 3 a) 2, 6-Di-t-butyl-4-methylphenoxydimethylchlorosilane A mixture of 2,6-di-t-butyl-4-methylphenol (110g,0.5M), acetonitrile (500ml), triethylamine (70ml,0.5M) and dichlorodimethylsilane (61 ml,0.5m) was refluxed for 16 hours. The solvent was evaporated and the residue extracted with toluene (500my). The toluene extract was evaporated and the residue recrystallised from acetonitrile to give the title compound (909,57%) m.p. 119-121"(Found: C,65 65; H,9.4%. C17 H29 ClOSi requires C,65.2; H,9.3%).
b) 2, 6-Di-t-butyl-4-methylphenoxydimethylsllyl isothiocyanate
A mixture of the silyl chloride (78g,0.25M), ammonium thiocyanate (26g,0.28M) and toluene was refluxed for 48 hours. The mixture was filtered and the filtrate evaporated; recrystallisation of the residue from acetonitrile gave the title compound (409,48%) m.p.83-4 . (Found: C,64.8; H,9.0; N,4.05. C18 H29 NOSSi requires: C,64.6; H,8.7; 4.2.)
Claims (32)
1. A process for preparing compounds of formula I
or acid addition salts thereof, wherein R1, R2, R3, R4 and R5 are the same or different and represent hydrogen or alkyl, cycloalkyl, aralkyl, or aryl radicals, any of which radicals may be substituted, or R1 and R2 taken together, or R2 and R3 taken together form a 5, 6, or 7 membered ring which may be saturated or unsaturated and substituted or unsubstituted, and when R1 and R2 form a ring, the ring has the same number of carbon atoms as the ring carrying X, R4 and R5 may also represent alkoxy, n is 1,2 or 3 and X is CN, CONH2, or
CSNH2 which process comprises treating a compound of formula II
wherein R1, R2, R3, R4, R5 and n are as defined in connection with formula I, and M is sodium, potassium, lithium, or MgHal, where Hal is chlorine, bromine or iodine, with a silyl compound of formula Ill, RXSi(NCY)4-x wherein Ra is selected from electron donating substituents including alkoxy, cycloalkoxy, aralkoxy, aryloxy, the group RbRCN-wherein Rb and RC are selected from alkyl, cycloalkyl, aryl and aralkyi or
Rb and Rc may be joined to form a heterocyclic ring with the nitrogen atom, alkylthio, cycloalkylthio, aralkylthio, arylthio and hydrocarbon substituents selected from alkyl, cycloalkyl, aralkyl or aryl, at least one group Ra being an electron donating substituent, Y is oxygen or sulphur, x has a value from 1 to 3, then subjecting the product to hydrolysis or alcoholysis, with the proviso that when a compound of formula I in which X is CN is desired the molar ratio of compound RXSi(NCY)4-xto compound II is at least 2::1 and xis 3 and Y is S and if desired isolating the product as an acid addition salt.
2. A process as claimed in Claim 1, when carried out in a solvent comprising an ether.
3. A process as claimed in Claim 2, wherein the ether solvent is a cyclic ether.
4. A process as claimed in Claim 3, wherein the ether solvent is tetrahydrofuran or dioxan.
5. A process as claimed in any one of claims 1 to 4, wherein the silyl compound Ill is R3SiNCY, wherein one group Ra is alkoxy of 1-10 carbon atoms or aryloxy and the other two are alkyl of 1-6 carbon atoms.
6. A process as claimed in Claim 5, wherein the silyl compound III is isopropoxydimethylsilyl isothiocyanate.
7. A process as claimed in Claim 5, wherein the silyl compound III is 2,6-di-t-butyl-4-methylphenoxydimethylsilyl isothiocyanate.
8. A process as claimed in any one of claims 1-4, wherein the siiyl compound Ill istri(dimethylamino)silyl isothiocyanate.
9. A process as claimed in any one of the preceding claims, wherein the starting compound of formula II is prepared in situ by reaction of a compound of formula II, where M is hydrogen with a metal amide.
10. A process as claimed in Claim 9, wherein the metal amide has the formula IV
wherein R14 is a straight or branched chain alkyl group of 1 to 6 carbon atoms or an aryl group, R71 is hydrogen, aryl or a tertiary alkyl group of 4 to 6 carbon atoms, R12 is aryl or a tertiary alkyl group of 4-6 carbon atoms, R13 is a branched chain alkyl group of 3 to 6 carbon atoms; X1 is lithium, sodium or potassium.
11. A process as claimed in Claim 10, wherein the metal amide is lithium N-t-butyl-N-(1 phenylpentyl)amide.
12. A process as claimed in any one of claims 1 to 11, wherein the compound offormula lisa tetrahydroquinoline derivative.
13. A compound of formula I, whenever prepared by a process as claimed in any one of claims 1-12.
14. A modification of the process claimed in any one of claims 1-l2for preparing nitriles offormula I, wherein X is CN, wherein 1 mol of a compound II, wherein M is lithium, sodium or potassium is reacted with 1 mol of compound Ill followed by one or more mols of a compound RxSiHa4~xwherein Ra and x are as defined previously and Hal is chlorine or bromine.
15. A nitrile of formula I whenever prepared by a process as claimed in Claim 14.
16. A compound of formula IIIA RxSi(NCY)4-x IIIA wherein Ra, x and Y are as defined in connection with formula Ill in Claim 1, with the provisos that: (i) when xis 3 and all three Ra groups are the same alkoxy then the alkoxy group has at least 3 carbon
atoms; (ii) when Ra is alkoxy and xis 1 then Ra is other than propoxy; (iii) when one or more Ra are alkylthio and the others (if any) are alkyl then the alkylthio group has at least
2 carbon atoms; (iv) when Ra is aryloxy and xis 3 then at least one group Ra is other than aryloxy.
17. A compound of formula IIIA as claimed in Claim 16, wherein one or two groups Ra are alkoxy or aryloxy, another group Ra is alkyl and xis 3.
18. A compound of formula IIIA as claimed in Claim 17, wherein one or more groups Ra are dialkylamino.
19. Dimethylmethoxysilyl isothiocyanate.
20. Dimethylisopropoxysilyl isothiocyanate.
21. Methyldimethoxysilyl isothiocyanate.
22. 2,6,Di-t-butyl-4-methyl phenoxydimethylsilyl isoth iocyanate.
23. Tri(dimethylamino)silyl isothiocyanate.
24. A process for preparing a compound of formula lIlA as claimed in any one of claims 16 to 18, which process comprises reacting a silylhalide RxSi(Hal)4~x wherein Hal is chlorine, bromine or iodine, and Ra and x are as defined in Claim 16, 17 or 18, with a thiocyanate or a cyanate.
25. A process as claimed in Claim 24, substantially as hereinbefore described in Example 1.
26. A process as claimed in claim 24, substantially as hereinbefore described in Example 3b.
27. A compound of formula IIIA, whenever prepared by a process as claimed in Claim 24, 25 or 26.
28. Acompound of formula Vl
wherein R1, R2, R3, R4, R5, Ra, n, x, Y and M are as defined in Claim 1.
29. Acompound of formula Vll
wherein R1, R2, R3, R4, R5, Ra, n, x and Y are as defined in Claim 1.
30. A process as claimed in claim 1, substantially as hereinbefore described in Example 2 (general method).
31. A process as claimed in Claim 1, substantially as hereinbefore described in Example 2 (any one of experiments a to k).
32. A compound of formula I, whenever prepared by a process as claimed in Claim 31.
Priority Applications (1)
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GB08316272A GB2122615B (en) | 1982-06-25 | 1983-06-15 | Preparation of fused carbocyclic ring derivatives of pyridine |
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Application Number | Priority Date | Filing Date | Title |
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GB8218464 | 1982-06-25 | ||
GB08316272A GB2122615B (en) | 1982-06-25 | 1983-06-15 | Preparation of fused carbocyclic ring derivatives of pyridine |
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GB8316272D0 GB8316272D0 (en) | 1983-07-20 |
GB2122615A true GB2122615A (en) | 1984-01-18 |
GB2122615B GB2122615B (en) | 1986-03-12 |
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Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1458148A (en) * | 1974-04-19 | 1976-12-08 | Wyeth John & Brother Ltd | Carbocyclic-fused ring quinoline derivatives |
GB1463666A (en) * | 1973-12-17 | 1977-02-02 | Wyeth John & Brother Ltd | Process for preparing fused carbocyclic ring derivatives of pyridine |
GB1463668A (en) * | 1974-03-27 | 1977-02-02 | Wyeth John & Brother Ltd | Carbocylic fused ring pyridine derivatives |
GB1463669A (en) * | 1974-03-27 | 1977-02-02 | Wyeth John & Brother Ltd | Tetrahydroquinoline derivatives |
GB1495993A (en) * | 1975-02-05 | 1977-12-21 | Wyeth John & Brother Ltd | Carbocyclic fused tetra hydroquinoline derivatives |
-
1983
- 1983-06-15 GB GB08316272A patent/GB2122615B/en not_active Expired
Patent Citations (5)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
GB1463666A (en) * | 1973-12-17 | 1977-02-02 | Wyeth John & Brother Ltd | Process for preparing fused carbocyclic ring derivatives of pyridine |
GB1463668A (en) * | 1974-03-27 | 1977-02-02 | Wyeth John & Brother Ltd | Carbocylic fused ring pyridine derivatives |
GB1463669A (en) * | 1974-03-27 | 1977-02-02 | Wyeth John & Brother Ltd | Tetrahydroquinoline derivatives |
GB1458148A (en) * | 1974-04-19 | 1976-12-08 | Wyeth John & Brother Ltd | Carbocyclic-fused ring quinoline derivatives |
GB1495993A (en) * | 1975-02-05 | 1977-12-21 | Wyeth John & Brother Ltd | Carbocyclic fused tetra hydroquinoline derivatives |
Also Published As
Publication number | Publication date |
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GB2122615B (en) | 1986-03-12 |
GB8316272D0 (en) | 1983-07-20 |
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