methyl 2-[(phenoxycarbonyl)oxy]acetate -Drug Synthesis Database

【结构式】

【分子编号】22341

【品名】methyl 2-[(phenoxycarbonyl)oxy]acetate

【CA登记号】

【分子式】C₁₀H₁₀O₅

【分子量】210.1864

【元素组成】C 57.14% H 4.8% O 38.06%

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：(VII)

Monoalkylation of 1,3-propanediamine (I) with 4-chlorobutanol (II) in refluxing n-BuOH afforded diaminoalcohol (III), which was protected as the bis-carbamate (IV) upon treatment with Boc2O. Subsequent reaction of (IV) with methanesulfonyl chloride and Et3N provided mesylate (V), and this was further treated with ethanolic ammonia to yield primary amine (VI). Condensation of amine (VI) with (methoxycarbonylmethyl) phenyl carbonate (VII) in refluxing toluene gave carbamate (VIII). Saponification of the methyl ester function of (VIII) then furnished carboxylic acid (IX). 1,6-Hexanediamine (X) was condensed with N,N'-bis(tert-butoxycarbonyl)-S-methylisothiourea (XI) to produce the (6-aminohexyl)guanidine derivative (XII). This was then coupled with carboxylic acid (IX) using DCC and HOBt. Finally, the N-Boc groups were deprotected with trifluoroacetic acid in CH2Cl2.

参考文献中间体

合成目标

【1】 Lebreton, L.; Annat, J.; Derrepas, P.; Dutartre, P.; Renaut, P.; Structure-immunosuppressive activity relationships of new analogues of 15-deoxyspergualin. 1. Structural modifications of the hydroxyglycine moiety. J Med Chem 1999, 42, 2, 277.

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)	19331	3-aminopropylamine; 1,3-propanediamine	109-76-2	C₃H₁₀N₂	详情	详情
(II)	22336	4-chloro-1-butanol	928-51-8	C₄H₉ClO	详情	详情
(III)	22337	4-[(3-aminopropyl)amino]-1-butanol		C₇H₁₈N₂O	详情	详情
(IV)	22338	tert-butyl 3-[(tert-butoxycarbonyl)amino]propyl(4-hydroxybutyl)carbamate		C₁₇H₃₄N₂O₅	详情	详情
(V)	22339	4-((tert-butoxycarbonyl)[3-[(tert-butoxycarbonyl)amino]propyl]amino)butyl methanesulfonate		C₁₈H₃₆N₂O₇S	详情	详情
(VI)	22340	tert-butyl 4-aminobutyl[3-[(tert-butoxycarbonyl)amino]propyl]carbamate		C₁₇H₃₅N₃O₄	详情	详情
(VII)	22341	methyl 2-[(phenoxycarbonyl)oxy]acetate		C₁₀H₁₀O₅	详情	详情
(VIII)	22342	methyl 9-(tert-butoxycarbonyl)-2,2-dimethyl-4,15-dioxo-3,16-dioxa-5,9,14-triazaoctadecan-18-oate		C₂₁H₃₉N₃O₈	详情	详情
(IX)	22343	9-(tert-butoxycarbonyl)-2,2-dimethyl-4,15-dioxo-3,16-dioxa-5,9,14-triazaoctadecan-18-oic acid		C₂₀H₃₇N₃O₈	详情	详情
(X)	22344	1,6-hexanediamine; 6-aminohexylamine	124-09-4	C₆H₁₆N₂	详情	详情
(XI)	22345	tert-butyl (E)-[(tert-butoxycarbonyl)amino](methylsulfanyl)methylidenecarbamate		C₁₂H₂₂N₂O₄S	详情	详情
(XII)	22346	tert-butyl (Z)-[(6-aminohexyl)amino][(tert-butoxycarbonyl)amino]methylidenecarbamate		C₁₇H₃₄N₄O₄	详情	详情

合成路线2

该中间体在本合成路线中的序号：(XII)

D-Alaninol (I) was protected as the tert-butyl carbamate (II) and then converted to mesylate (III). Displacement of the mesylate group of (III) with NaCN furnished nitrile (IV), which was hydrogenated over Raney Nickel to give diamine (V). Condensation of (V) with benzaldehyde (VI) in the presence of molecular sieves produced imine (VII) and subsequent reduction by means of NaBH4 gave rise to the benzyl amine (VIII). This amine was alkylated with 4-chlorobutyronitrile (IX) to afford nitrile (X), which was further converted to the triamino compound (XI) by hydrogenation over Raney Nickel. Reaction of (XI) with methyl 2-[(phenoxycarbonyl)oxy]acetate (XII) provided carbamate (XIII). The ester group of (XIII) was then hydrolyzed with NaOH to give carboxylic acid (XIV).

参考文献中间体

合成目标

【1】 Lebreton, L.; et al.; Structure - Immunosuppressive activity relationships of new analogues of 15-deoxyspergualin. 2. Structural modifications of the spermidine moiety. J Med Chem 1999, 42, 23, 4749.

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)	21414	(2R)-2-Amino-1-propanol; D-Alaninol; D-(-)-Alaninol	35320-23-1	C₃H₉NO	详情	详情
(II)	31758	tert-butyl (1R)-2-hydroxy-1-methylethylcarbamate		C₈H₁₇NO₃	详情	详情
(III)	31803	(2R)-2-[(tert-butoxycarbonyl)amino]propyl methanesulfonate		C₉H₁₉NO₅S	详情	详情
(IV)	31804	tert-butyl (1R)-2-cyano-1-methylethylcarbamate		C₉H₁₆N₂O₂	详情	详情
(V)	31805	tert-butyl (1R)-3-amino-1-methylpropylcarbamate		C₉H₂₀N₂O₂	详情	详情
(VI)	10498	Benzaldehyde;Benzoic aldehyde;Phenylmethanal	100-52-7	C₇H₆O	详情	详情
(VII)	31806	tert-butyl (1R)-1-methyl-3-[[(E)-benzylidene]amino]propylcarbamate		C₁₆H₂₄N₂O₂	详情	详情
(VIII)	31807	tert-butyl (1R)-3-(benzylamino)-1-methylpropylcarbamate		C₁₆H₂₆N₂O₂	详情	详情
(IX)	11179	4-Chlorobutanenitrile; 4-Chlorobutyronitrile	628-20-6	C₄H₆ClN	详情	详情
(X)	31808	tert-butyl (1R)-3-[benzyl(3-cyanopropyl)amino]-1-methylpropylcarbamate		C₂₀H₃₁N₃O₂	详情	详情
(XI)	31809	tert-butyl (1R)-3-[(4-aminobutyl)(benzyl)amino]-1-methylpropylcarbamate		C₂₀H₃₅N₃O₂	详情	详情
(XII)	22341	methyl 2-[(phenoxycarbonyl)oxy]acetate		C₁₀H₁₀O₅	详情	详情
(XIII)	31810	methyl (6R)-9-benzyl-2,2,6-trimethyl-4,15-dioxo-3,16-dioxa-5,9,14-triazaoctadecan-18-oate		C₂₄H₃₉N₃O₆	详情	详情
(XIV)	31811	(6R)-9-benzyl-2,2,6-trimethyl-4,15-dioxo-3,16-dioxa-5,9,14-triazaoctadecan-18-oic acid		C₂₃H₃₇N₃O₆	详情	详情

Extended Information