(2R)-2-(4-methoxyphenyl)-2-(4-nitro-1H-imidazol-1-yl)propanoyl chloride -Drug Synthesis Database

【结构式】

【分子编号】35767

【品名】(2R)-2-(4-methoxyphenyl)-2-(4-nitro-1H-imidazol-1-yl)propanoyl chloride

【CA登记号】

【分子式】C₁₃H₁₂ClN₃O₄

【分子量】309.7088

【元素组成】C 50.42% H 3.91% Cl 11.45% N 13.57% O 20.66%

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：(XIX)

4-Methoxyphenylacetic acid (XI) was esterified using EtOH and p-toluenesulfonic acid, and then brominated with NBS to give bromoester (XII). Coupling of (XII) with 4-nitroimidazole (XIII) afforded adduct (XIV), which was alkylated using iodomethane and NaH to yield (XVa-b). Hydrolysis of the ester group of (XVa-b) with LiOH gave the corresponding carboxylic acid, which was converted to acid chloride (XVIa-b) by means of treatment with oxalyl chloride. Reaction of (XVI) with the lithium salt of the chiral oxazolidinone (XVII) provided a diastereomeric mixture of N-acyloxazolidinones, which were separated by silica gel chromatography. Removal of the chiral auxiliary from the desired isomer (XVIII) under basic conditions, followed by treatment with oxalyl chloride provided acid chloride (XIX). Further reaction of (XIX) with pyrrolidine (XX) produced amide (XXI). Reduction of the nitro group of (XXI) using hydrogen and Pd/C generated the aminoimidazole derivative (XXII). This was coupled with the N-Boc-dipeptide (X) affording amide (XXIII). The Boc protecting group of (XXIII) was then cleaved by treatment with trifluoroacetic acid, and the title compound was finally isolated as the dihydrochloride salt.

参考文献中间体

合成目标

【1】 Growth hormone secretagogues. EP 0933365; WO 9908699 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XVa)	35766	ethyl (2R)-2-(4-methoxyphenyl)-2-(4-nitro-1H-imidazol-1-yl)propanoate		C₁₅H₁₇N₃O₅	详情	详情
(XVIa)	35767	(2R)-2-(4-methoxyphenyl)-2-(4-nitro-1H-imidazol-1-yl)propanoyl chloride		C₁₃H₁₂ClN₃O₄	详情	详情
(XVIb)	35768	(2S)-2-(4-methoxyphenyl)-2-(4-nitro-1H-imidazol-1-yl)propanoyl chloride		C₁₃H₁₂ClN₃O₄	详情	详情
(XVb)	35769	ethyl (2R)-2-(4-methoxyphenyl)-2-(4-nitro-1H-imidazol-1-yl)propanoate		C₁₅H₁₇N₃O₅	详情	详情
(X)	18473	(2R)-2-([2-[(tert-butoxycarbonyl)amino]-2-methylpropanoyl]amino)-5-phenylpentanoic acid		C₂₀H₃₀N₂O₅	详情	详情
(XI)	34793	2-(4-methoxyphenyl)acetic acid; p-Methoxyphenyl formate; Homoanisic acid; p-Methyl benzyl formate; 4-methoxyphenylacetic acid; 4-methoxybenzeneacetic acid; p-methoxyphenylacetic acid	104-01-8	C₉H₁₀O₃	详情	详情
(XII)	35763	ethyl 2-bromo-2-(4-methoxyphenyl)acetate	77053-56-6	C₁₁H₁₃BrO₃	详情	详情
(XIII)	35764	4-nitro-1H-imidazole	3034-38-6	C₃H₃N₃O₂	详情	详情
(XIV)	35765	ethyl 2-(4-methoxyphenyl)-2-(4-nitro-1H-imidazol-1-yl)acetate		C₁₄H₁₅N₃O₅	详情	详情
(XVII)	35770			C₁₀H₁₀LiNO₂	详情	详情
(XVIII)	35771	(4R,5S)-3-[(2R)-2-(4-methoxyphenyl)-2-(4-nitro-1H-imidazol-1-yl)propanoyl]-4-methyl-5-phenyl-1,3-oxazolidin-2-one		C₂₃H₂₂N₄O₆	详情	详情
(XIX)	35767	(2R)-2-(4-methoxyphenyl)-2-(4-nitro-1H-imidazol-1-yl)propanoyl chloride		C₁₃H₁₂ClN₃O₄	详情	详情
(XX)	11376	Pyrrolidine	123-75-1	C₄H₉N	详情	详情
(XXI)	35772	(2R)-2-(4-methoxyphenyl)-2-(4-nitro-1H-imidazol-1-yl)-1-(1-pyrrolidinyl)-1-propanone		C₁₇H₂₀N₄O₄	详情	详情
(XXII)	35773	(2R)-2-(4-amino-1H-imidazol-1-yl)-2-(4-methoxyphenyl)-1-(1-pyrrolidinyl)-1-propanone		C₁₇H₂₂N₄O₂	详情	详情
(XXIII)	35774	tert-butyl 2-([(1R)-1-[([1-[(1R)-1-(4-methoxyphenyl)-1-methyl-2-oxo-2-(1-pyrrolidinyl)ethyl]-1H-imidazol-4-yl]amino)carbonyl]-4-phenylbutyl]amino)-1,1-dimethyl-2-oxoethylcarbamate		C₃₇H₅₀N₆O₆	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XVIa)

参考文献中间体

合成目标

【1】 Growth hormone secretagogues. EP 0933365; WO 9908699 .

中间体序号	中间体编号	品名	CAS号	分子式	供应商	用于合成
(XVa)	35766	ethyl (2R)-2-(4-methoxyphenyl)-2-(4-nitro-1H-imidazol-1-yl)propanoate		C₁₅H₁₇N₃O₅	详情	详情
(XVIa)	35767	(2R)-2-(4-methoxyphenyl)-2-(4-nitro-1H-imidazol-1-yl)propanoyl chloride		C₁₃H₁₂ClN₃O₄	详情	详情
(XVIb)	35768	(2S)-2-(4-methoxyphenyl)-2-(4-nitro-1H-imidazol-1-yl)propanoyl chloride		C₁₃H₁₂ClN₃O₄	详情	详情
(XVb)	35769	ethyl (2R)-2-(4-methoxyphenyl)-2-(4-nitro-1H-imidazol-1-yl)propanoate		C₁₅H₁₇N₃O₅	详情	详情
(X)	18473	(2R)-2-([2-[(tert-butoxycarbonyl)amino]-2-methylpropanoyl]amino)-5-phenylpentanoic acid		C₂₀H₃₀N₂O₅	详情	详情
(XI)	34793	2-(4-methoxyphenyl)acetic acid; p-Methoxyphenyl formate; Homoanisic acid; p-Methyl benzyl formate; 4-methoxyphenylacetic acid; 4-methoxybenzeneacetic acid; p-methoxyphenylacetic acid	104-01-8	C₉H₁₀O₃	详情	详情
(XII)	35763	ethyl 2-bromo-2-(4-methoxyphenyl)acetate	77053-56-6	C₁₁H₁₃BrO₃	详情	详情
(XIII)	35764	4-nitro-1H-imidazole	3034-38-6	C₃H₃N₃O₂	详情	详情
(XIV)	35765	ethyl 2-(4-methoxyphenyl)-2-(4-nitro-1H-imidazol-1-yl)acetate		C₁₄H₁₅N₃O₅	详情	详情
(XVII)	35770			C₁₀H₁₀LiNO₂	详情	详情
(XVIII)	35771	(4R,5S)-3-[(2R)-2-(4-methoxyphenyl)-2-(4-nitro-1H-imidazol-1-yl)propanoyl]-4-methyl-5-phenyl-1,3-oxazolidin-2-one		C₂₃H₂₂N₄O₆	详情	详情
(XIX)	35767	(2R)-2-(4-methoxyphenyl)-2-(4-nitro-1H-imidazol-1-yl)propanoyl chloride		C₁₃H₁₂ClN₃O₄	详情	详情
(XX)	11376	Pyrrolidine	123-75-1	C₄H₉N	详情	详情
(XXI)	35772	(2R)-2-(4-methoxyphenyl)-2-(4-nitro-1H-imidazol-1-yl)-1-(1-pyrrolidinyl)-1-propanone		C₁₇H₂₀N₄O₄	详情	详情
(XXII)	35773	(2R)-2-(4-amino-1H-imidazol-1-yl)-2-(4-methoxyphenyl)-1-(1-pyrrolidinyl)-1-propanone		C₁₇H₂₂N₄O₂	详情	详情
(XXIII)	35774	tert-butyl 2-([(1R)-1-[([1-[(1R)-1-(4-methoxyphenyl)-1-methyl-2-oxo-2-(1-pyrrolidinyl)ethyl]-1H-imidazol-4-yl]amino)carbonyl]-4-phenylbutyl]amino)-1,1-dimethyl-2-oxoethylcarbamate		C₃₇H₅₀N₆O₆	详情	详情

Extended Information