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【结 构 式】

【分子编号】25662

【品名】tert-butyl 4-[2-[4-(3,10-dibromo-8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-1-piperidinyl]-2-oxoethyl]-1-piperidinecarboxylate

【CA登记号】

【 分 子 式 】C31H36Br2ClN3O3

【 分 子 量 】693.90596

【元素组成】C 53.66% H 5.23% Br 23.03% Cl 5.11% N 6.06% O 6.92%

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:(VIII)

Benzocycloheptapyridine (I) was nitrated with NaNO3 and H2SO4 to afford (II) as the major isomer. Reduction of (II) with iron and CaCl2 gave amine (III), which was brominated to provide (IV). Removal of the amino group of (IV) was accomplished by diazotization, followed by reduction with hypophosphorous acid to give (V). Then, hydrolysis of the carbamate group in refluxing hydrochloric acid furnished piperidine (VI). Subsequent coupling of (VI) with N-Boc-piperidineacetic acid (VII) using EDC and HOBt yielded amide (VIII). After Boc deprotection of (VIII) with trifluoroacetic acid, piperidine (IX) was condensed with trimethylsilyl isocyanate to produce the corresponding urea. Finally, separation of the target (+)-atropoisomer was achieved by chiral chromatography.

1 (+)-4-[2-[4-(8-Chloro-3,10-dibromo-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridin-11(R)-yl)-1-piperidinyl]-2-oxo-ethyl]-1-piperidinecarboxamide (SCH-66336): A very potent farnesyl protein transferase inhibitor as a novel antitumor agent. J Med Chem 1998, 41, 24, 4890.
2 Bishop, W.R.; Girijavallabhan, V.M.; Njoroge, F.G.; Bryant, M.S.; Nomeir, A.A.; Doll, R.J.; Ganguly, A.K.; Kirschmeier, P.; Liu, M.; Vibulbhan, B.; Atropisomeric trihalobenzocycloheptapyridine analogues provide stereoselective FPT inhibitors with antitumor activity. Bioorg Med Chem 1999, 7, 5, 861.
中间体序号 中间体编号 品名 CAS号 分子式 供应商 用于合成
19976 isocyanato(trimethyl)silane; trimethylsilyl isocyanate C4H9NOSi 详情 详情
(I) 19338 ethyl 4-(3-bromo-8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-1-piperidinecarboxylate C22H22BrClN2O2 详情 详情
(II) 19340 ethyl 4-(3-bromo-8-chloro-9-nitro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-1-piperidinecarboxylate C22H21BrClN3O4 详情 详情
(III) 19341 ethyl 4-(9-amino-3-bromo-8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-1-piperidinecarboxylate C22H23BrClN3O2 详情 详情
(IV) 19342 ethyl 4-(9-amino-3,10-dibromo-8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-1-piperidinecarboxylate C22H22Br2ClN3O2 详情 详情
(V) 19343 ethyl 4-(3,10-dibromo-8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-1-piperidinecarboxylate C22H21Br2ClN2O2 详情 详情
(VI) 19344 3,10-dibromo-8-chloro-11-(4-piperidinylidene)-6,11-dihydro-5H-benzo[5,6]cyclohepta[1,2-b]pyridine C19H17Br2ClN2 详情 详情
(VII) 19346 1-Boc-piperidin-4-ylacetic acid; 2-[1-(tert-butoxycarbonyl)-4-piperidinyl]acetic acid 157688-46-5 C12H21NO4 详情 详情
(VIII) 25662 tert-butyl 4-[2-[4-(3,10-dibromo-8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-1-piperidinyl]-2-oxoethyl]-1-piperidinecarboxylate C31H36Br2ClN3O3 详情 详情
(IX) 25663 1-[4-(3,10-dibromo-8-chloro-5,6-dihydro-11H-benzo[5,6]cyclohepta[1,2-b]pyridin-11-ylidene)-1-piperidinyl]-2-(4-piperidinyl)-1-ethanone C26H28Br2ClN3O 详情 详情
Extended Information