(2R,3S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)butyric acid -Drug Synthesis Database

【结构式】

【分子编号】28255

【品名】(2R,3S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)butyric acid

【CA登记号】

【分子式】C₁₇H₂₂N₂O₄

【分子量】318.37276

【元素组成】C 64.13% H 6.97% N 8.8% O 20.1%

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：(I)

Coupling of N-Boc-beta-methyltryptophan (I) with N-Cbz-lysine tert-butyl ester (II) using EDC and HOBt afforded dipeptide (III). Selective deprotection of the Boc group of (III) with methanesulfonic acid gave amine (IV). This was converted to urea (VI) upon treatment with benzimidazolylpiperidine (V) and N,N'-disuccinimidyl carbonate in the presence of diisopropyl ethylamine. The N-carbobenzoxy group of (VI) was finally deprotected by hydrogenolysis over Pd/C.

参考文献中间体

合成目标

【1】 Synthesis and biological activities of potent peptidomimetics selective for somatostatin receptor subtype 2. Proc Natl Acad Sci USA 1998, 95, 18, 10836.
【2】 Berk, S.; Yang, L.; Chen, M.H.; Johnston, D.; Pasternak, A.; Chapman, K.; Guo, L.; Nargund, R.; Tata, J.R.; Patchett, A.A. (Merck & Co., Inc.); Somatostatin agonists. EP 0984779; US 6063796; WO 9844922 .

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)	28255	(2R,3S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)butyric acid		C₁₇H₂₂N₂O₄	详情	详情
(II)	21879	tert-butyl (2S)-2-amino-6-[[(benzyloxy)carbonyl]amino]hexanoate		C₁₈H₂₈N₂O₄	详情	详情
(III)	28256	tert-butyl (2S)-6-[[(benzyloxy)carbonyl]amino]-2-[[(2R,3S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)butanoyl]amino]hexanoate		C₃₅H₄₈N₄O₇	详情	详情
(IV)	28257	tert-butyl (2S)-2-[[(2R,3S)-2-amino-3-(1H-indol-3-yl)butanoyl]amino]-6-[[(benzyloxy)carbonyl]amino]hexanoate		C₃₀H₄₀N₄O₅	详情	详情
(V)	12138	1-(4-Piperidinyl)-1,3-dihydro-2H-benzimidazol-2-one; 4-(2-Keto-1-benzimidazolinyl)piperidine	20662-53-7	C₁₂H₁₅N₃O	详情	详情
(VI)	28258	tert-butyl (2S)-6-[[(benzyloxy)carbonyl]amino]-2-[[(2R,3S)-3-(1H-indol-3-yl)-2-([[4-(2-oxo-2,3-dihydro-1H-benzimidazol-1-yl)-1-piperidinyl]carbonyl]amino)butanoyl]amino]hexanoate		C₄₃H₅₃N₇O₇	详情	详情

合成路线2

该中间体在本合成路线中的序号：(I)

Treatment of (Boc)-beta-methyltryptophan (I) with SOCl2 and MeOH produced beta-methyltryptophan methyl ester (II). 3,3-Diphenylpropylamine (III) was protected with Boc2O and then alkylated with allyl bromide in the presence of potassium hexamethyldisilazide to afford (IV). Further ozonization of the allyl double bond of (IV) generated the aminoaldehyde (V). Amino ester (II) was reductively alkylated with aldehyde (V) in the presence of NaBH3CN to yield the protected diamine (VI). After acid deprotection of the Boc group of (VI), the resulting diamine (VII) was converted to imidazolinone (VIII) upon treatment with phosgene and diisopropylethylamine. Subsequent hydrolysis of the methyl ester of (VIII) gave carboxylic acid (IX).

参考文献中间体

合成目标

【1】 Marino, D.; Pan, Y.; Pasternak, A.; et al.; Potent, orally bioavailable somatostatin agonists: Good absorption achieved by urea backbone cyclization. Bioorg Med Chem Lett 1999, 9, 3, 491.

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)	28255	(2R,3S)-2-[(tert-butoxycarbonyl)amino]-3-(1H-indol-3-yl)butyric acid		C₁₇H₂₂N₂O₄	详情	详情
(II)	29274	methyl (2R,3S)-2-amino-3-(1H-indol-3-yl)butanoate		C₁₃H₁₆N₂O₂	详情	详情
(III)	29275	3,3-diphenyl-1-propanamine	5586-73-2	C₁₅H₁₇N	详情	详情
(IV)	29276	tert-butyl allyl(3,3-diphenylpropyl)carbamate		C₂₃H₂₉NO₂	详情	详情
(V)	29277	tert-butyl 3,3-diphenylpropyl(2-oxoethyl)carbamate		C₂₂H₂₇NO₃	详情	详情
(VI)	29278	methyl (2R,3S)-2-([2-[(tert-butoxycarbonyl)(3,3-diphenylpropyl)amino]ethyl]amino)-3-(1H-indol-3-yl)butanoate		C₃₅H₄₃N₃O₄	详情	详情
(VII)	29279	methyl (2R,3S)-2-([2-[(3,3-diphenylpropyl)amino]ethyl]amino)-3-(1H-indol-3-yl)butanoate		C₃₀H₃₅N₃O₂	详情	详情
(VIII)	29280	methyl (2R,3S)-2-[3-(3,3-diphenylpropyl)-2-oxo-1-imidazolidinyl]-3-(1H-indol-3-yl)butanoate		C₃₁H₃₃N₃O₃	详情	详情
(IX)	29281	(2R,3S)-2-[3-(3,3-diphenylpropyl)-2-oxo-1-imidazolidinyl]-3-(1H-indol-3-yl)butyric acid		C₃₀H₃₁N₃O₃	详情	详情

Extended Information