2-[bis(2-hydroxyethyl)amino]-1-ethanol -Drug Synthesis Database

【结构式】

【分子编号】28168

【品名】2-[bis(2-hydroxyethyl)amino]-1-ethanol

【CA登记号】102-71-6

【分子式】C₆H₁₅NO₃

【分子量】149.19004

【元素组成】C 48.3% H 10.13% N 9.39% O 32.17%

与该中间体有关的原料药合成路线共 3 条

合成路线1 合成路线2 合成路线3

合成路线1

该中间体在本合成路线中的序号：(VI)

The esterification of N-methylpyrrol-2-carboxylic acid (I) with NaH and methyl iodide in DMF gives methyl N methylpyrrol 2 carboxylate (II), which is condensed with acetonitrile by means of NaH in DMF yielding 3-(1-methyl-2-pyrrolyl)-3-oxopropionitrile (III). The reaction of (III) with phenylisocyanate (IV) by means of triethylamine in toluene affords 2-cyano-3-(1-methyl-2-pyrrolyl)-3-oxo-N-phenylpropionamide (V), which is finally treated with triethanolamine (VI) in hot ethanol.

参考文献中间体

合成目标

【1】 Walker, G.N. (Novartis AG); alpha-Carbamoyl-pyrrolpropionitriles, process fortheir preparation and pharmaceutical preparations containing them. EP 0143142 .
【2】 Serradell, M.N.; Castaner, J.; Castaner, R.M.; Prinomide Triethanolamine. Drugs Fut 1987, 12, 8, 773.

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)	11286	1-Methyl-1H-pyrrole-2-carboxylic acid; 1-Methyl-2-pyrrolecarboxylic acid	6973-60-0	C₆H₇NO₂	详情	详情
(II)	11287	methyl 1-methyl-1H-pyrrole-2-carboxylate	37619-24-2	C₇H₉NO₂	详情	详情
(III)	11288	3-(1-Methyl-1H-pyrrol-2-yl)-3-oxopropanenitrile		C₈H₈N₂O	详情	详情
(IV)	11289	1-Isocyanatobenzene; phenyl isocyanate; Phenylisocyanate	103-71-9	C₇H₅NO	详情	详情
(V)	28167	2-cyano-3-(1-methyl-1H-pyrrol-2-yl)-3-oxo-N-phenylpropanamide		C₁₅H₁₃N₃O₂	详情	详情
(VI)	28168	2-[bis(2-hydroxyethyl)amino]-1-ethanol	102-71-6	C₆H₁₅NO₃	详情	详情

合成路线2

该中间体在本合成路线中的序号：(VI)

The reaction of acid (I) with SOCl2 in ethyl ether containing triethylamine gives the corresponding acyl chloride (VII), which is condensed with ethyl cyanacetate (VIII) by means of NaH in glyme yielding ethyl 2-cyano-3-(1-methyl-2-pyrrolyl)-3-oxopropanoate (IX). The reaction of (IX) with aniline (X) in refluxing xylene affords the corresponding anilide (V) already obtained.

参考文献中间体

合成目标

【1】 Walker, G.N. (Novartis AG); alpha-Carbamoyl-pyrrolpropionitriles, process fortheir preparation and pharmaceutical preparations containing them. EP 0143142 .
【2】 Serradell, M.N.; Castaner, J.; Castaner, R.M.; Prinomide Triethanolamine. Drugs Fut 1987, 12, 8, 773.

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)	11286	1-Methyl-1H-pyrrole-2-carboxylic acid; 1-Methyl-2-pyrrolecarboxylic acid	6973-60-0	C₆H₇NO₂	详情	详情
(V)	28167	2-cyano-3-(1-methyl-1H-pyrrol-2-yl)-3-oxo-N-phenylpropanamide		C₁₅H₁₃N₃O₂	详情	详情
(VI)	28168	2-[bis(2-hydroxyethyl)amino]-1-ethanol	102-71-6	C₆H₁₅NO₃	详情	详情
(VII)	28169	1-methyl-1H-pyrrole-2-carbonyl chloride		C₆H₆ClNO	详情	详情
(VIII)	11877	Cyanoacetic acid ethyl ester; Ethyl 2-cyanoacetate; Ethyl cyanoacetate; Ethyl isocyanacetate	105-56-6	C₅H₇NO₂	详情	详情
(IX)	28170	ethyl 2-cyano-3-(1-methyl-1H-pyrrol-2-yl)-3-oxopropanoate		C₁₁H₁₂N₂O₃	详情	详情
(X)	12294	Aniline; Phenylamine	62-53-3	C₆H₇N	详情	详情

合成路线3

该中间体在本合成路线中的序号：(III)

Activation of N-Boc-beta-alanine (I) as the mixed anhydride (II) with isobutyl chloroformate, followed by condensation with triethanolamine (III), furnished the [bis(2-hydroxyethyl)amino]ethyl ester (IV). Silylation of the free hydroxyl groups of (IV) by means of tert-butyldimethylsilyl chloride and imidazole afforded the bis-silylether (V). The N-Boc protecting group of (V) was then selectively removed upon treatment with trifluoroacetic acid to give amino ester (VI). This was subsequently coupled with 9-methoxyacridine (VII), yielding adduct (VIII), which was further desilylated with HF/pyridine. The resultant bis(hydroxyethyl) derivative (IX) was finally converted to the target dichloro compound by treatment with thionyl chloride.

参考文献中间体

合成目标

【1】 Wollowitz, S.; Rapoport, H.; Cook, D.; Merritt, J.; Neiro, A.; Stassinopoulos, A.; Matejovic, J. (Cerus Corp.); Frangible cpds. for pathogen inactivation. WO 9830545 .

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)	26616	N-(tert-butoxycarbonyl)-beta-alanine	3303-84-2	C₈H₁₅NO₄	详情	详情
(II)	52945		n/a	C₁₃H₂₃NO₆	详情	详情
(III)	28168	2-[bis(2-hydroxyethyl)amino]-1-ethanol	102-71-6	C₆H₁₅NO₃	详情	详情
(IV)	52946	2-[bis(2-hydroxyethyl)amino]ethyl 3-[(tert-butoxycarbonyl)amino]propanoate	n/a	C₁₄H₂₈N₂O₆	详情	详情
(V)	52947	2-[bis(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)amino]ethyl 3-[(tert-butoxycarbonyl)amino]propanoate	n/a	C₂₆H₅₆N₂O₆Si₂	详情	详情
(VI)	52948	2-[bis(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)amino]ethyl 3-aminopropanoate	n/a	C₂₁H₄₈N₂O₄Si₂	详情	详情
(VII)	52949	9-acridinyl methyl ether; 9-methoxyacridine	n/a	C₁₄H₁₁NO	详情	详情
(VIII)	52950	2-[bis(2-{[tert-butyl(dimethyl)silyl]oxy}ethyl)amino]ethyl 3-(9-acridinylamino)propanoate	n/a	C₃₄H₅₅N₃O₄Si₂	详情	详情
(IX)	52951	2-[bis(2-hydroxyethyl)amino]ethyl 3-(9-acridinylamino)propanoate	n/a	C₂₂H₂₇N₃O₄	详情	详情

Extended Information