1,1-dimethylethyl 3-aminopropylcarbamate -Drug Synthesis Database

【结构式】

【分子编号】52474

【品名】1,1-dimethylethyl 3-aminopropylcarbamate

【CA登记号】

【分子式】C₈H₁₈N₂O₂

【分子量】174.2432

【元素组成】C 55.15% H 10.41% N 16.08% O 18.36%

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：(II)

The monoprotection of propane-1,3-diamine (I) with Boc2O in dichloromethane gives the N-(3-aminopropyl)carbamic acid tert-butyl ester (II), which is condensed with vinylphosphonic acid diethyl ester (III) to yield the aminoethylphosphonic ester derivative (IV). The condensation of (IV) with 3,4-diethoxycyclobutene-1,2-dione (V) in ethanol affords the disubstituted 2-aminoethylphosphonic ester derivative (VI), which is cyclized by means of trifluoroacetic acid in dichloromethane to provide the bicyclic phosphonic ester (VII). Finally, the phosphonic ester group of (VII) is hydrolyzed by means of trimethylsilyl bromide in dichloromethane to furnish the target phosphonic acid.

参考文献中间体

合成目标

【1】 Kinney, W.A.; Schmid, J.; Asselin, A.A. (Wyeth); Process for the preparation of [2-((8.9)-dioxo-2,6-diazabicyclo[5.2.0]-non-1(7)-en-2-yl)ethyl]phosphonic acid. US 5990307 .
【2】 Kinney, W.A.; Schmid, J.; Asselin, A.A. (Wyeth); Process for the preparation of [2-((8,9)-dioxo-2,6-diazabicyclo[5.2.0]-non-1(7)-en-2-yl)-ethyl]phosphonic acid. WO 9906417 .

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)	52474	1,1-dimethylethyl 3-aminopropylcarbamate		C₈H₁₈N₂O₂	详情	详情
(III)	54644	diethyl vinylphosphonate		C₆H₁₃O₃P	详情	详情
(IV)	54645	diethyl 2-({3-[(tert-butoxycarbonyl)amino]propyl}amino)ethylphosphonate		C₁₄H₃₁N₂O₅P	详情	详情
(V)	30975	3,4-diethoxy-3-cyclobutene-1,2-dione	5231-87-8	C₈H₁₀O₄	详情	详情
(VI)	54646	diethyl 2-[{3-[(tert-butoxycarbonyl)amino]propyl}(2-ethoxy-3,4-dioxo-1-cyclobuten-1-yl)amino]ethylphosphonate		C₂₀H₃₅N₂O₈P	详情	详情
(VII)	54142	diethyl 2-[8,9-dioxo-2,6-diazabicyclo[5.2.0]non-1(7)-en-2-yl]ethylphosphonate	n/a	C₁₃H₂₁N₂O₅P	详情	详情

合成路线2

该中间体在本合成路线中的序号：(II)

Condensation of tert-butyl 4-fluoro-3-(bromomethyl)benzoate (I) with N-Boc-1,3-propanediamine (II) afforded the aminomethyl benzoate derivative (III). This was coupled with N-Cbz-L-aspartic acid beta-methyl ester (IV), yielding amide (V). After hydrogenolysis of the carbobenzoxy protecting group of (V), the resultant fluoro amine (VI) was cyclized to the benzodiazepinone (VII) upon treatment with 2,6-di-tert-butylpyridine in hot NMP. Acidic cleavage of both the tert-butyl ester and the N-Boc groups of (VII), followed by reprotection of the amine with Boc2O, furnished the N-Boc acid (VIII). This was then coupled to 2-(methylaminomethyl)benzimidazole (IX) to afford, after acidic Boc group cleavage, the amino amide (X).

参考文献中间体

合成目标

【1】 Cheesman, E.H.; et al.; Nonpeptide vitronectin antagonists labeled with Tc99m for imaging tumors. 222nd ACS Natl Meet (Aug 26 2001, Chicago) 2001, Abst MEDI 77.
【2】 Sworin, M.; Cheesman, E.H.; Rajopadhyem, M. (DuPont Pharmaceuticals Co.); Vitronectin receptor antagonist pharmaceuticals. EP 1140864; WO 0035887 .

中间体序号	中间体编号	品名	分子式	供应商	用于合成
(I)	52473	1,1-dimethylethyl 3-(bromomethyl)-4-fluorobenzoate	C₁₂H₁₄BrFO₂	详情	详情
(II)	52474	1,1-dimethylethyl 3-aminopropylcarbamate	C₈H₁₈N₂O₂	详情	详情
(III)	52475	1,1-dimethylethyl 3-({[3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)propyl]amino}methyl)-4-fluorobenzoate	C₂₀H₃₁FN₂O₄	详情	详情
(IV)	52476	O-methyl-4-oxo-N-{[(phenylmethyl)oxy]carbonyl}homoserine	C₁₃H₁₅NO₆	详情	详情
(V)	52477	1,1-dimethylethyl 3-({[3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)propyl][4-(methyloxy)-4-oxo-2-({[(phenylmethyl)oxy]carbonyl}amino)butanoyl]amino}methyl)-4-fluorobenzoate	C₃₃H₄₄FN₃O₉	详情	详情
(VI)	52478	1,1-dimethylethyl 3-({[2-amino-4-(methyloxy)-4-oxobutanoyl][3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)propyl]amino}methyl)-4-fluorobenzoate	C₂₅H₃₈FN₃O₇	详情	详情
(VII)	52479	1,1-dimethylethyl 4-[3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)propyl]-2-[2-(methyloxy)-2-oxoethyl]-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-7-carboxylate	C₂₅H₃₇N₃O₇	详情	详情
(VIII)	52480	4-[3-({[(1,1-dimethylethyl)oxy]carbonyl}amino)propyl]-2-[2-(methyloxy)-2-oxoethyl]-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepine-7-carboxylic acid	C₂₁H₂₉N₃O₇	详情	详情
(IX)	52481	1H-benzimidazol-2-yl-N-methylmethanamine; N-(1H-benzimidazol-2-ylmethyl)-N-methylamine	C₉H₁₁N₃	详情	详情
(X)	52482	methyl 2-(4-(3-aminopropyl)-7-{[(1H-benzimidazol-2-ylmethyl)(methyl)amino]carbonyl}-3-oxo-2,3,4,5-tetrahydro-1H-1,4-benzodiazepin-2-yl)acetate	C₂₅H₃₀N₆O₄	详情	详情

Extended Information