合成路线:The condensation of S-methylisothiourea (I) with trans-4-(aminomethyl)cyclohexanecarboxylic acid (II) by means of NaOH in water gives trans-4-(guanidinomethyl)cyclohexanecarboxylic acid (III) (I),which is esterified with benzyl salicylate (IV) by means of dicyclohexylcarbodiimide (DCC) or SOCl2 yielding 2-benzyloxycarbonylphenyl trans-4-(guanidinomethyl)cyclohexanecarboxylate (V).Finally,this compound is treated with cyclodextrin in aqueous solution to afford the corresponding complex.
合成路线:1) By carboxylation of 8-chloro-6,11-dihydro-11-(4-piperidylidene)-5H-benzo[5,6]cyctohepta[1,2-b]pyridine (I) with ethyl chloroformate (II) in refluxing benzene.
合成路线:2) By reaction of 8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-one (III) with the Grignard reagent (IV) to give the tertiary carbinol (V),which is dehydrated with 85% H2SO4 affording 8-chloro-11-piperidinylidene derivative (VI).Finally,cornpound (VI) is treated with ethyl chloroformate (II) in toluene.
合成路线:Alcoholysis of 3-methylpyridine-2-carbonitrile (I) with hot tert-butanol and H2SO4 gives the N-tert-butylcarboxamide (II),which is alkylated with 3-chlorobenzyl chloride (III) and BuLi in THF,yielding N-tert-butyl-3-[2-(3-chlorophenyl)ethyl]pyridine-2-carboxamide (IV).The reaction of (IV) with refluxing POCl3 and then with NaOH affords the corresponding nitrile (V),which is condensed with 1-methylpiperidin-4-ylmagnesium chloride (VI) in THF to give the ketone (VII).Cyclization of (VII) by means of either BF3 in HF or trifluoromethanesulfonic acid yields 8-chloro-11-(1-methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine (VIII),which is reacted with cyanogen bromide in benzene to give the N-cyano compound (IX).Finally,this compound is treated with HCl in refluxing acetic acid/water.Alternatively,8-chloro-11-(1-methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine (VIII) is treated with ethyl chloroformate in hot toluene,affording the carbamate (X) (2),which is finally decarboxylated with KOH or NaOH in refluxing ethanol/water.
参考文献标题:Antihistaminic 11-(4-piperidylidene)-5H-benzo-[5,6
文献作者:Villani,F.J.(Schering Corp.)
参考来源:US 4282233
合成路线:Condensation of ethyl nicotinate (XI) with 3-chlorophenylacetonitrile (XII) by means of sodium ethoxide in ethanol gives 2-(3-chlorophenyl)-3-oxo-3-(3-pyridyl)propionitrile (XIII),which by refluxing with concentrated HBr yields 2-(3-chlorophenyl)-1-(3-pyridyl)ethanone (XIV).The reduction of (XIV) with hydrazine hydrate and NaOH in diethylene glycol at 235-40 C affords 3-(2-phenylethyl) pyridine (XV),which is oxidized with H2O2 in hot acetic acid to provide the corresponding N-oxide (XVI).Reaction of (XVI) with NaCN and dimethyl sulfate in water affords the previously described 3-(2-phenylethyl)pyridine-2-carbonitrile (V),which can be worked up as previously described or cyclized with polyphosphoric acid (PPA) at 180 C to give 8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-one (XVII).The condensation of (XVII) with 1-methylpiperidin-4-ylmagnesium chloride (VI) in THF yields the corresponding carbinol (XVIII),which is dehydrated with PPA at 170 C to afford the previously reported 8-chloro-11-(1-methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine (VIII).
参考文献标题:Novel aza-dibenzo[a,d]cycloheptene derivatives
文献作者:Villani,F.J.(Schering Corp.)
参考来源:US 3326924
合成路线:Alcoholysis of 3-methylpyridine-2-carbonitrile (I) with hot tert-butanol and H2SO4 gives the N-tert-butylcarboxamide (II),which is alkylated with 3-chlorobenzyl chloride (III) and BuLi in THF,yielding N-tert-butyl-3-[2-(3-chlorophenyl)ethyl]pyridine-2-carboxamide (IV).The reaction of (IV) with refluxing POCl3 and then with NaOH affords the corresponding nitrile (V),which is condensed with 1-methylpiperidin-4-ylmagnesium chloride (VI) in THF to give the ketone (VII).Cyclization of (VII) by means of either BF3 in HF or trifluoromethanesulfonic acid yields 8-chloro-11-(1-methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine (VIII),which is reacted with cyanogen bromide in benzene to give the N-cyano compound (IX).Finally,this compound is treated with HCl in refluxing acetic acid/water.Alternatively,8-chloro-11-(1-methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine (VIII) is treated with ethyl chloroformate in hot toluene,affording the carbamate (X) (2),which is finally decarboxylated with KOH or NaOH in refluxing ethanol/water.
合成路线:Condensation of ethyl nicotinate (XI) with 3-chlorophenylacetonitrile (XII) by means of sodium ethoxide in ethanol gives 2-(3-chlorophenyl)-3-oxo-3-(3-pyridyl)propionitrile (XIII),which by refluxing with concentrated HBr yields 2-(3-chlorophenyl)-1-(3-pyridyl)ethanone (XIV).The reduction of (XIV) with hydrazine hydrate and NaOH in diethylene glycol at 235-40 C affords 3-(2-phenylethyl) pyridine (XV),which is oxidized with H2O2 in hot acetic acid to provide the corresponding N-oxide (XVI).Reaction of (XVI) with NaCN and dimethyl sulfate in water affords the previously described 3-(2-phenylethyl)pyridine-2-carbonitrile (V),which can be worked up as previously described or cyclized with polyphosphoric acid (PPA) at 180 C to give 8-chloro-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-one (XVII).The condensation of (XVII) with 1-methylpiperidin-4-ylmagnesium chloride (VI) in THF yields the corresponding carbinol (XVIII),which is dehydrated with PPA at 170 C to afford the previously reported 8-chloro-11-(1-methylpiperidin-4-ylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine (VIII).
参考文献标题:Desloratadine
文献作者:Castar,J.; Leeson,P.; Graul,A.
参考来源:Drugs Fut 2000,25(4),339
产品链接: CAS No. 100643-71-8››