2-[[(2S)-2-amino-3-phenylpropyl]oxy]-1-ethanol -Drug Synthesis Database

【结构式】

【分子编号】30455

【品名】2-[[(2S)-2-amino-3-phenylpropyl]oxy]-1-ethanol

【CA登记号】

【分子式】C₁₁H₁₇NO₂

【分子量】195.26152

【元素组成】C 67.66% H 8.78% N 7.17% O 16.39%

与该中间体有关的原料药合成路线共 2 条

合成路线1 合成路线2

合成路线1

该中间体在本合成路线中的序号：(VII)

The condensation of N-(tert-butoxycarbonyl)-4-nitro-L-phenylalanine (I) with 4-ethylpiperiine (II) by means of diisopropylethylamine (DIEA) in dichloromethane gives the corresponding protected piperidide (III), which is treated with TFA to eliminate the carbamate group yielding (IV). The sulfonation of (IV) with 4-chloropyridine-3-sulfonyl chloride (V) by means of DIEA in dichloromethane affords the sulfonamide (VI), which is condensed with 2-(2(S)-amino-3-phenylpropoxy)ethanol (VII) by means of DIEA in ethanol giving the intermediate (VIII). Finally, the reduction of the nitro group of (VIII) with H2 over Pd/C in methanol affords the target compound.

参考文献中间体

合成目标

【1】 Brundish, D.E.; Brown, L.N.; Le Grand, D.M.; Menear, K.A.; Smith, G.P.; Allen, M.C.; Butler, P.I.; Cockroft, X.-L.; Matthews, I.T.W.; Walker, C.V.; Wathey, W.B. (Novartis AG); Thrombin inhibitors. WO 9746553 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	28516	(2S)-2-[(tert-butoxycarbonyl)amino]-3-(4-nitrophenyl)propionic acid	C₁₄H₁₈N₂O₆	详情	详情
(II)	30451	4-ethylpiperidine	C₇H₁₅N	详情	详情
(III)	30452	tert-butyl (1S)-2-(4-ethyl-1-piperidinyl)-1-(4-nitrobenzyl)-2-oxoethylcarbamate	C₂₁H₃₁N₃O₅	详情	详情
(IV)	30453	(2S)-2-amino-1-(4-ethyl-1-piperidinyl)-3-(4-nitrophenyl)-1-propanone	C₁₆H₂₃N₃O₃	详情	详情
(V)	28521	4-chloro-3-pyridinesulfonyl chloride	C₅H₃Cl₂NO₂S	详情	详情
(VI)	30454	4-chloro-N-[(1S)-2-(4-ethyl-1-piperidinyl)-1-(4-nitrobenzyl)-2-oxoethyl]-3-pyridinesulfonamide	C₂₁H₂₅ClN₄O₅S	详情	详情
(VII)	30455	2-[[(2S)-2-amino-3-phenylpropyl]oxy]-1-ethanol	C₁₁H₁₇NO₂	详情	详情
(VIII)	30456	4-[[(1S)-1-benzyl-2-(2-hydroxyethoxy)ethyl]amino]-N-[(1S)-2-(4-ethyl-1-piperidinyl)-1-(4-nitrobenzyl)-2-oxoethyl]-3-pyridinesulfonamide	C₃₂H₄₁N₅O₇S	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VII)

The intermediate 2-(2(S)-amino-3-phenylpropoxy)ethanol (VII) has been obtained as follows: The condensation of 2(S)-(dibenzylamino)-3-phenyl-1-propanol (IX) with tert-butyl 2-bromoacetate (X) by means of tetrabutylammonium hydrogen sulfate and NaOH in dichloromethane/water gives 2-[2(S)-(dibenzylamino)-3-phenylpropoxy]acetic acid tert-butyl ester (XI), which is reduced with LiAlH4 in THF yielding 2-[2(S)-(dibenzylamino)-3-phenylpropoxy]ethanol (XII). Finally, this compound is debenzylated by hydrogenation with H2 over Pd/C in methanol/acetic acid affording the target intermediate (VII).

参考文献中间体

合成目标

【1】 Brundish, D.E.; Brown, L.N.; Le Grand, D.M.; Menear, K.A.; Smith, G.P.; Allen, M.C.; Butler, P.I.; Cockroft, X.-L.; Matthews, I.T.W.; Walker, C.V.; Wathey, W.B. (Novartis AG); Thrombin inhibitors. WO 9746553 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VII)	30455	2-[[(2S)-2-amino-3-phenylpropyl]oxy]-1-ethanol		C₁₁H₁₇NO₂	详情	详情
(IX)	30457	(2S)-2-(dibenzylamino)-3-phenyl-1-propanol	111060-52-7	C₂₃H₂₅NO	详情	详情
(X)	17430	2-Bromoacetic acid tert-butyl ester; tert-butyl 2-bromoacetate; tert-Butyl bromoacetate	5292-43-3	C₆H₁₁BrO₂	详情	详情
(XI)	30458	tert-butyl 2-[[(2S)-2-(dibenzylamino)-3-phenylpropyl]oxy]acetate		C₂₉H₃₅NO₃	详情	详情
(XII)	30459	2-[[(2S)-2-(dibenzylamino)-3-phenylpropyl]oxy]-1-ethanol		C₂₅H₂₉NO₂	详情	详情

Extended Information