benzyl (2R,3R)-3-methoxy-2-methyl-3-[(2S)pyrrolidinyl]propanoate -Drug Synthesis Database

【结构式】

【分子编号】23504

【品名】benzyl (2R,3R)-3-methoxy-2-methyl-3-[(2S)pyrrolidinyl]propanoate

【CA登记号】

【分子式】C₁₆H₂₃NO₃

【分子量】277.36356

【元素组成】C 69.29% H 8.36% N 5.05% O 17.31%

与该中间体有关的原料药合成路线共 1 条

合成路线1

该中间体在本合成路线中的序号：(V)

1) The reaction of tert-butoxycarbonyl-L-prolinal (I) with benzyl propionate (II) by means of lithium diisopropylamide (LDA) in THF gives a mixture of isomers that is separated by flash chromatography, yielding the (2R,3R)-isomer (III). The methylation of (III) with diazomethane and boron trifluoride ethearate or NaH and methyl iodide affords the methoxy derivative (IV), which is deprotected with HCl in dioxane, giving (V). The condensation of (V) with tripeptide (VI) by means of diethyl phosphorocyanidate (DEPC) in DMF yields the tetrapeptide benzyl ester (VII), which is finally debenzylated by hydrogenolysis over Pd/C in tert-butanol and amidated with 2-phenylethylamine (VIII) and DEPC and triethylamine in DMF.

参考文献中间体

合成目标

【1】 Tsukagoshi, S.; Sakakibara, K.; Gondo, M.; Natsume, T.; Mikami, T.; Kobayashi, M.; Miyazaki, K.; Synthesis and antitumor activity of novel dolastat. Chem Pharm Bull 1995, 43, 10, 1706.
【2】 Castañer, J.; Leeson, P.; Hoshi, A.; TZT-1027. Drugs Fut 1999, 24, 4, 404.
【3】 Sakakibara, K.; Gondo, M.; Miyazaki, K. (Teikoku Hormone Manufacturing Co., Ltd.); Novel tetrapeptide derivs.. EP 0598129; JP 1993503479; US 5654399; WO 9303054 .

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)	16724	tert-Butyl (2S)-2-formyltetrahydro-1H-pyrrole-1-carboxylate; tert-Butoxycarbonyl-L-prolinal	69610-41-9	C₁₀H₁₇NO₃	详情	详情
(II)	23501	benzyl propionate	122-63-4	C₁₀H₁₂O₂	详情	详情
(III)	23502	tert-butyl (2S)-2-[(1R,2R)-3-(benzyloxy)-1-hydroxy-2-methyl-3-oxopropyl]-1-pyrrolidinecarboxylate		C₂₀H₂₉NO₅	详情	详情
(IV)	23503	tert-butyl (2S)-2-[(1R,2R)-3-(benzyloxy)-1-methoxy-2-methyl-3-oxopropyl]-1-pyrrolidinecarboxylate		C₂₁H₃₁NO₅	详情	详情
(V)	23504	benzyl (2R,3R)-3-methoxy-2-methyl-3-[(2S)pyrrolidinyl]propanoate		C₁₆H₂₃NO₃	详情	详情
(VI)	23505	(3R,4S,5S)-4-[((2S)-2-[[(2S)-2-(dimethylamino)-3-methylbutanoyl]amino]-3-methylbutanoyl)(methyl)amino]-3-methoxy-5-methylheptanoic acid		C₂₂H₄₃N₃O₅	详情	详情
(VII)	23506	benzyl (2R,3R)-3-((2S)-1-[(3R,4S,5S)-4-[((2S)-2-[[(2S)-2-(dimethylamino)-3-methylbutanoyl]amino]-3-methylbutanoyl)(methyl)amino]-3-methoxy-5-methylheptanoyl]pyrrolidinyl)-3-methoxy-2-methylpropanoate		C₃₈H₆₄N₄O₇	详情	详情
(VIII)	18333	Phenethylamine; 2-Phenyl-1-ethanamine	64-04-0	C₈H₁₁N	详情	详情

Extended Information