【结 构 式】 |
【分子编号】15848 【品名】tert-butyl N-methyl-N-[2-(methylamino)ethyl]carbamate 【CA登记号】 |
【 分 子 式 】C9H20N2O2 【 分 子 量 】188.27008 【元素组成】C 57.42% H 10.71% N 14.88% O 17% |
合成路线1
该中间体在本合成路线中的序号:(IV)By condensation of 2(S)-[N-methyl-N-[2-[N-methyl-N-(morpholinocarbonyl)amino]ethyl]carbamoyloxy]-3-phenylpropanoic acid (I) with protected Nalpha-methyl-L-histidine 1(S)-(cyclohexylmethyl)-2(S)-hydroxy-5-methylhexylamide (II) by means of oxalyl chloride and DMF in dichloromethane. The starting compounds (I) and (II) are obtained as follows: 1) The reaction of morpholinocarbonyl chloride (III) with N-(tert-butoxycarbonyl)-N,N'-dimethylethylenediamine (IV) by means of triethylamine in dichloromethane gives the monoacylated diamine (V), which is deprotected with trifluoroacetic acid to yield N,N'-dimethyl-N-(morpholinocarbonyl)ethylenediamine (VI). The condensation of (VI) with 2(S)-hydroxy-3-phenylpropanoic acid benzyl ester (VII) by means of trichloromethyl chloroformate in refluxing THF affords 2(S)-[N-methyl-N-[2-[N-methyl-N-(morpholinocarbonyl)amino]ethyl]carbamoyloxy]propanoic acid benzyl ester (VIII), which is finally debenzylated by hydrogenation with H2 over Pd/C to give (I). 2) The Grignard reaction of tert-butoxycarbonyl-(3-cyclohexyl)-L-alaninal (IX) with 3-methylbutylmagnesium bromide (X) in THF gives 2(S)-(tert-butoxycarbonylamino)-1-cyclohexyl-3(S)-hydroxy-6-methylheptane (XI), which is deprotected with trifluoroacetic acid to yield the free amine derivative (XII). The condensation of (XII) with Nalpha-(tert-butoxycarbonyl)-Nalpha-methyl-Ntau-tosyl-L-histidine (XIII) by means of N-ethyl-N'-[3-(dimethylamino)propyl]carbodiimide (CDI) in dichloromethane affords the corresponding histidinamide (XIV), which is deprotected with trifluoroacetic acid to afford (II).
【1】 Hemmi, K.; Neya, M.; Marusawa, H.; Imai, K.; Kayakiri, N.; Hashimoto, M. (Fujisawa Pharmaceutical Co., Ltd.); New amino acid derivs. processes for the preparation thereof and pharmaceutical compsns. containing the same. AU 8818190; EP 0300189; JP 1989019071; US 4921855; US 5223489 . |
【2】 Prous, J.; Castaner, J.; FK-906. Drugs Fut 1993, 18, 4, 312. |
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) | 15845 | (2S)-2-[[(methyl[2-[methyl(morpholinocarbonyl)amino]ethyl]amino)carbonyl]oxy]-3-phenylpropionic acid | C19H27N3O6 | 详情 | 详情 | |
(II) | 15846 | (2S)-N-[(1S,2S)-1-(cyclohexylmethyl)-2-hydroxy-5-methylhexyl]-2-(methylamino)-3-[1-[(4-methylphenyl)sulfonyl]-1H-imidazol-4-yl]propanamide | C28H44N4O4S | 详情 | 详情 | |
(III) | 15847 | 4-morpholinecarbonyl chloride; Morpholine-4-carbonyl chloride | 15159-40-7 | C5H8ClNO2 | 详情 | 详情 |
(IV) | 15848 | tert-butyl N-methyl-N-[2-(methylamino)ethyl]carbamate | C9H20N2O2 | 详情 | 详情 | |
(V) | 15849 | tert-butyl N-methyl-N-[2-[methyl(morpholinocarbonyl)amino]ethyl]carbamate | C14H27N3O4 | 详情 | 详情 | |
(VI) | 15850 | N-methyl-N-[2-(methylamino)ethyl]-4-morpholinecarboxamide | C9H19N3O2 | 详情 | 详情 | |
(VII) | 15851 | Benzyl (s)-(-)-2-hydroxy-3-phenylpropionate; benzyl (2S)-2-hydroxy-3-phenylpropanoate | 7622-21-1 | C16H16O3 | 详情 | 详情 |
(VIII) | 15852 | benzyl (2S)-2-[[(methyl[2-[methyl(morpholinocarbonyl)amino]ethyl]amino)carbonyl]oxy]-3-phenylpropanoate | C26H33N3O6 | 详情 | 详情 | |
(IX) | 15853 | tert-butyl N-[(1S)-2-cyclohexyl-1-formylethyl]carbamate | C14H25NO3 | 详情 | 详情 | |
(X) | 13532 | Bromo(isopentyl)magnesium | C5H11BrMg | 详情 | 详情 | |
(XI) | 15855 | tert-butyl N-[(1S,2S)-1-(cyclohexylmethyl)-2-hydroxy-5-methylhexyl]carbamate | C19H37NO3 | 详情 | 详情 | |
(XII) | 15856 | (2S,3S)-2-amino-1-cyclohexyl-6-methyl-3-heptanol | C14H29NO | 详情 | 详情 | |
(XIII) | 15857 | (2S)-2-[(tert-butoxycarbonyl)(methyl)amino]-3-[1-[(4-methylphenyl)sulfonyl]-1H-imidazol-4-yl]propionic acid | C19H25N3O6S | 详情 | 详情 | |
(XIV) | 15858 | tert-butyl (1S)-2-[[(1S,2S)-1-(cyclohexylmethyl)-2-hydroxy-5-methylhexyl]amino]-1-([1-[(4-methylphenyl)sulfonyl]-1H-imidazol-4-yl]methyl)-2-oxoethyl(methyl)carbamate | C33H52N4O6S | 详情 | 详情 |