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【结 构 式】

【分子编号】34056

【品名】8-chloro-11-(1-cyano-4-piperidinylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine

【CA登记号】

【 分 子 式 】C20H18ClN3

【 分 子 量 】335.83584

【元素组成】C 71.53% H 5.4% Cl 10.56% N 12.51%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号:(IX)

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.

1 Villani, F.J.; Wong, J.K. (Schering Corp.); Antihistaminic 8-(halo)-substituted 6,11-dihydro-11-(4-piperidylidene)-5H-benzo[5,6]cyclohepta[1,2-b]pyridines. WO 8503707 .
2 Castaner, J.; Leeson, P.; Graul, A.; Desloratadine. Drugs Fut 2000, 25, 4, 339.
3 Villani, F.J. (Schering Corp.); Antihistaminic 11-(4-piperidylidene)-5H-benzo-[5,6. US 4282233 .
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
(I) 16500 3-methyl-2-pyridinecarbonitrile 20970-75-6 C7H6N2 详情 详情
(II) 16501 N-(tert-butyl)-3-methyl-2-pyridinecarboxamide C11H16N2O 详情 详情
(III) 20642 1-chloro-3-(chloromethyl)benzene; 3-Chlorobenzyl chloride 620-20-2 C7H6Cl2 详情 详情
(IV) 20643 N-(tert-butyl)-3-(3-chlorophenethyl)-2-pyridinecarboxamide C18H21ClN2O 详情 详情
(V) 20644 3-(3-chlorophenethyl)-2-pyridinecarbonitrile C14H11ClN2 详情 详情
(VI) 20645 chloro(1-methyl-4-piperidinyl)magnesium C6H12ClMgN 详情 详情
(VII) 20646 [3-(3-chlorophenethyl)-2-pyridinyl](1-methyl-4-piperidinyl)methanone C20H23ClN2O 详情 详情
(VIII) 20647 8-chloro-11-(1-methyl-4-piperidinylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine 38092-89-6 C20H21ClN2 详情 详情
(IX) 34056 8-chloro-11-(1-cyano-4-piperidinylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine C20H18ClN3 详情 详情
(X) 17877 ethyl 4-(8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-1-piperidinecarboxylate 79794-75-5 C22H23ClN2O2 详情 详情
Extended Information