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【结 构 式】

【分子编号】45629

【品名】4-amino-2,3,5-trimethylphenol

【CA登记号】

【 分 子 式 】C9H13NO

【 分 子 量 】151.20836

【元素组成】C 71.49% H 8.67% N 9.26% O 10.58%

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:(I)

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).

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