-Drug Synthesis Database

【结构式】

【药物名称】

【化学名称】(2R,3S)-N-(trans-5-Amino-1,3-dioxan-2-ylmethyl)-3-(3-indolyl)-2-[3-(3,3-diphenylpropyl)-2-oxo-1-imidazolidinyl]butyramide

【CA登记号】

【分子式】C₃₅H₄₁N₅O₄

【分子量】595.74812

【开发单位】Merck & Co. (Originator)

【药理作用】ENDOCRINE DRUGS, Pituitary Disorder Therapy, Treatment of Growth Hormone Excess, Treatment of Growth Hormone Secretion Disorders, Somatostatin SRIF1A (sst2) Agonists

合成路线1 合成路线2

合成路线1

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

【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

合成路线2

Coupling of (IX) with monoprotected diamine (X) by means of EDC and HOBt to furnish amide (XI). Finally, deprotecion of the amino group of (XI) afforded the title compound.

参考文献中间体

【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	分子式	供应商	用于合成
(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
(X)	29282	benzyl 2-(aminomethyl)-1,3-dioxan-5-ylcarbamate	C₁₃H₁₈N₂O₄	详情	详情
(XI)	29283	benzyl 2-([[(2R,3S)-2-[3-(3,3-diphenylpropyl)-2-oxo-1-imidazolidinyl]-3-(1H-indol-3-yl)butanoyl]amino]methyl)-1,3-dioxan-5-ylcarbamate	C₄₃H₄₇N₅O₆	详情	详情

Extended Information

Drug NewChemical Entity Original Patent(1)