tert-butyl (2S)-2-[2-(acetoxy)acetyl]tetrahydro-1H-pyrrole-1-carboxylate -Drug Synthesis Database

【结构式】

【分子编号】16736

【品名】tert-butyl (2S)-2-[2-(acetoxy)acetyl]tetrahydro-1H-pyrrole-1-carboxylate

【CA登记号】

【分子式】C₁₃H₂₁NO₅

【分子量】271.31348

【元素组成】C 57.55% H 7.8% N 5.16% O 29.49%

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：(XIII)

2) The reaction of tert-butoxycarbonyl-L-proline (XI) with diazomethane and triethylamine in ether gives the diazoketone (XII), which by treatment with acetic acid at 100 C yields the acetoxyketone (XIII). The deprotection of (XIII) with trifluoroacetic acid affords the unprotected alpha-hydroxyketone (XIV), which is condensed with N-(benzylaminecarbonyl)-L-proline (VI) by means of 1-hydroxybenzotriazole (HOBT) giving the acetylated dipeptide analogue (XV). Finally, this compound is deacetylated with K2CO3 in methanol/water.

参考文献中间体

合成目标

【1】 Wroblewski, T.; Silvestre, J.S.; Castañer, J.; JTP-4819. Drugs Fut 1998, 23, 4, 384.
【2】 Kobayashi, K.; Akamatsu, M.; Yata, S.; Abe, H.; Toide, K.; Kogayu, M.; Uchida, I. (Japan Tobacco Inc.; Welfide Corporation); Cpd. with prolyl endopeptidase inhibitor activity and pharmaceutical use thereof. EP 0670309; JP 1995512967; US 5536737; WO 9412474 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(VI)	16729	(2S)-1-[(benzylamino)carbonyl]tetrahydro-1H-pyrrole-2-carboxylic acid		C₁₃H₁₆N₂O₃	详情	详情
(XI)	16734	(2S)-1-(tert-butoxycarbonyl)tetrahydro-1H-pyrrole-2-carboxylic acid; N-alpha-t-BOC-L-proline; (2S)-1-(tert-butoxycarbonyl)-2-pyrrolidinecarboxylic acid		C₁₀H₁₇NO₄	详情	详情
(XII)	16735	tert-butyl (2S)-2-(2-diazoacetyl)tetrahydro-1H-pyrrole-1-carboxylate	101130-03-4	C₁₁H₁₇N₃O₃	详情	详情
(XIII)	16736	tert-butyl (2S)-2-[2-(acetoxy)acetyl]tetrahydro-1H-pyrrole-1-carboxylate		C₁₃H₂₁NO₅	详情	详情
(XIV)	16737	2-oxo-2-[(2S)tetrahydro-1H-pyrrol-2-yl]ethyl acetate		C₈H₁₃NO₃	详情	详情
(XV)	16738	2-[(2S)-1-([(2S)-1-[(benzylamino)carbonyl]tetrahydro-1H-pyrrol-2-yl]carbonyl)tetrahydro-1H-pyrrol-2-yl]-2-oxoethyl acetate		C₂₁H₂₇N₃O₅	详情	详情

合成路线2

该中间体在本合成路线中的序号：(IV)

L-Proline (I) is protected as its N-Boc derivative (II) with Boc2O/NaOH in a two-phase system. N-Boc-Proline (II) is further converted into diazo ketone (III) via activation with ethyl chloroformate, followed by condensation with diazomethane. Subsequent treatment of diazo ketone (III) with AcOH leads to the acetoxy ketone (IV). Then, acidic N-Boc group cleavage in (IV) furnishes amine (V). On the other side, L-proline (I) is acylated by 4-phenylbutyryl chloride to produce the corresponding amide (VI). Coupling between 2-(acetoxyacetyl)pyrrolidine (V) and N-(phenylbutyryl)proline (VI) via activation with pivaloyl chloride leads to the amide adduct (VII). Finally, methanolysis of the acetate ester group of (VII) provides the target hydroxyacetyl compound.

参考文献中间体

合成目标

【1】 Wallén, E.A.; Christiaans, J.A.M.; Saario, S.M.; Forsberg, M.M.; Venalainen, J.I.; Paso, H.M.; Mannisto, P.T.; Gynther, J.; 4-Phenylbutanoyl-2(S)-acylpyrrolidines and 4-phenylbutanoyl-L-prolyl-2(S)-acylpyrrolidines as prolyl oligopeptidase inhibitors. Bioorg Med Chem 2002, 10, 7, 2199.

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)	16131	methyl 4-(butyrylamino)-3-methylbenzoate		C₁₃H₁₇NO₃	详情	详情
(II)	16734	(2S)-1-(tert-butoxycarbonyl)tetrahydro-1H-pyrrole-2-carboxylic acid; N-alpha-t-BOC-L-proline; (2S)-1-(tert-butoxycarbonyl)-2-pyrrolidinecarboxylic acid		C₁₀H₁₇NO₄	详情	详情
(III)	64266	(L)-2-Diazoacetyl-pyrrolidine-1-carboxylic acid tertiary-butyl ester (L)-2-Diazoacetyl-pyrrolidine-1-carboxylic acid tertiary-butyl ester (L)-2-Diazoacetyl-pyrrolidine-1-carboxylic acid tertiary-butyl ester	101130-03-4	C₁₁H₁₇N₃O₃	详情	详情
(IV)	16736	tert-butyl (2S)-2-[2-(acetoxy)acetyl]tetrahydro-1H-pyrrole-1-carboxylate		C₁₃H₂₁NO₅	详情	详情
(V)	16737	2-oxo-2-[(2S)tetrahydro-1H-pyrrol-2-yl]ethyl acetate		C₈H₁₃NO₃	详情	详情
(VI)	64267	(2S)-1-(4-phenylbutanoyl)-2-pyrrolidinecarboxylic acid		C₁₅H₁₉NO₃	详情	详情
(VII)	64268	2-oxo-2-((2S)-1-{[(2S)-1-(4-phenylbutanoyl)pyrrolidinyl]carbonyl}pyrrolidinyl)ethyl acetate		C₂₃H₃₀N₂O₅	详情	详情

Extended Information