tert-butyl 4-[((2S)-3-[4-[4-(4-fluorobenzyl)phenyl]-1-piperazinyl]-2-hydroxypropyl)oxy]-2,3,6-trimethylphenylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】45636

【品名】tert-butyl 4-[((2S)-3-[4-[4-(4-fluorobenzyl)phenyl]-1-piperazinyl]-2-hydroxypropyl)oxy]-2,3,6-trimethylphenylcarbamate

【CA登记号】

【分子式】C₃₄H₄₄FN₃O₄

【分子量】577.7395832

【元素组成】C 70.68% H 7.68% F 3.29% N 7.27% O 11.08%

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)

Chemoselective protection of the amino group of 2,3,5-trimethyl-4-aminophenol (I) with di-tert-butyl dicarbonate (Boc)2O in THF gives compound (II), which is then treated with NaH and (S)-glycidyl 3-nitrobenzenesulfonate (III) to yield epoxypropane (IV). On the other hand, treatment of 4,4'-difluorobenzophenone (V) with piperazine (VI) in acetonitrile in the presence of Et3N gives derivative (VII), which is reduced with Et3siH in the presence of H2SO4 and TFA to afford piperazine (VIII). Condensation of epoxypropane (IV) with piperazine (VIII) in refluxing 2-propanol furnishes compound (IX), which is finally converted into the desired product by first removal of the Boc group by exposure to TFA in CH2Cl2, followed by treatment with methanesulfonic acid (MeSO3H).

参考文献中间体

合成目标

【2】 Nakanishi, K.; Annoura, H.; Tamura, S. (Suntory Ltd.); Arylpiperidinopropanol and arylpiperazinopropanol derivs. and pharmaceuticals containing the same. CA 2276373; EP 0958280; WO 9923072 .
【1】 Tamura-Horikawa, Y.; Miyajima, A.; Tamura, S.; Annoura, H.; Imajo, S.; Toba, T.; Takemoto, N.; Nakanishi, K.; Discovery of (2S)-1-(4-amino-2,3,5-trimethylphenoxy)-3-(4-[4-(4-fluorobenzyl)phenyl)-1-piperazinyl)-2-propanol dimethanesulfonate (SUN N8075): A dual Na+ and Ca2+ channel blocker with antioxidant activity. J Med Chem 2000, 43, 18, 3372.

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)	45629	4-amino-2,3,5-trimethylphenol		C₉H₁₃NO	详情	详情
(II)	45630	tert-butyl 4-hydroxy-2,3,6-trimethylphenylcarbamate		C₁₄H₂₁NO₃	详情	详情
(III)	45631	(2S)oxiranylmethyl 4-nitrobenzenesulfonate		C₉H₉NO₆S	详情	详情
(IV)	45632	tert-butyl 2,3,6-trimethyl-4-[(2S)oxiranylmethoxy]phenylcarbamate		C₁₇H₂₅NO₄	详情	详情
(V)	45633	bis(4-fluorophenyl)methanone; 4,4'-Difluorobenzophenone	345-92-6	C₁₃H₈F₂O	详情	详情
(VI)	10355	Diethylenediamine; Piperazine	110-85-0	C₄H₁₀N₂	详情	详情
(VII)	45634	(4-fluorophenyl)[4-(1-piperazinyl)phenyl]methanone		C₁₇H₁₇FN₂O	详情	详情
(VIII)	45635	1-[4-(4-fluorobenzyl)phenyl]piperazine		C₁₇H₁₉FN₂	详情	详情
(IX)	45636	tert-butyl 4-[((2S)-3-[4-[4-(4-fluorobenzyl)phenyl]-1-piperazinyl]-2-hydroxypropyl)oxy]-2,3,6-trimethylphenylcarbamate		C₃₄H₄₄FN₃O₄	详情	详情

Extended Information