【结 构 式】 |
【分子编号】62875 【品名】allyl 5-[3-(5-{[(allyloxy)carbonyl]amino}-4-{[(2S,4R)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-hydroxypyrrolidinyl]carbonyl}-2-methoxyphenoxy)propoxy]-2-{[(2S,4R)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-hydroxypyrrolidinyl]carbonyl}-4-metho 【CA登记号】 |
【 分 子 式 】C49H76N4O14Si2 【 分 子 量 】1001.332 【元素组成】C 58.78% H 7.65% N 5.6% O 22.37% Si 5.61% |
合成路线1
该中间体在本合成路线中的序号:(VIII)The nitration of the dimeric benzoic acid (I) with 70% HNO3 gives the dimeric nitrobenzoic acid (II), which is treated with oxalyl chloride in THF to yield the acid chloride (III). The reaction of (III) with the pyrrolidine (IV) by means of TEA in the same solvent affords the diamide (V). The reduction of the nitro groups of (V) with RaNI and hydrazine in methanol provides the diamino compound (VI), which is protected with allyloxycarbonyl chloride (VII) and pyridine in dichloromethane to give the bis carbamate (VIII). The oxidation of the OH groups of (VIII) with oxalyl chloride and TEA in DMSO/dichloromethane yields the bis-pyrrolidinone (IX), which is allowed to react with methyl triphenylphosphonium bromide (X) and tBu-OK in THF to afford the bis exomethylene derivative (XI).
【1】 Gregson, S.J.; Howard, P.W.; Corcoran, K.E.; Jenkins, T.C.; Kelland, L.R.; Thurston, D.E.; Synthesis of the first example of a C2-C3/C2'-C3'-endo unsaturated pyrrolo[2,1-c][1,4]benzodiazepine dimer. Bioorg Med Chem Lett 2001, 11, 21, 2859. |
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) | 47736 | 4-[3-(4-carboxy-2-methoxyphenoxy)propoxy]-3-methoxybenzoic acid | C19H20O8 | 详情 | 详情 | |
(II) | 47737 | 4-[3-(4-carboxy-2-methoxy-5-nitrophenoxy)propoxy]-5-methoxy-2-nitrobenzoic acid | C19H18N2O12 | 详情 | 详情 | |
(III) | 47738 | 4-[3-[4-(chlorocarbonyl)-2-methoxy-5-nitrophenoxy]propoxy]-5-methoxy-2-nitrobenzoyl chloride | C19H16Cl2N2O10 | 详情 | 详情 | |
(IV) | 62872 | (3R,5S)-5-({[tert-butyl(dimethyl)silyl]oxy}methyl)-3-pyrrolidinol | C11H25NO2Si | 详情 | 详情 | |
(V) | 62873 | [(2S,4R)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-hydroxypyrrolidinyl]{4-[3-(4-{[(2S,4R)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-hydroxypyrrolidinyl]carbonyl}-2-methoxy-5-nitrophenoxy)propoxy]-5-methoxy-2-nitrophenyl}methanone | C41H64N4O14Si2 | 详情 | 详情 | |
(VI) | 62874 | {2-amino-4-[3-(5-amino-4-{[(2S,4R)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-hydroxypyrrolidinyl]carbonyl}-2-methoxyphenoxy)propoxy]-5-methoxyphenyl}[(2S,4R)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-hydroxypyrrolidinyl]methanone | C41H68N4O10Si2 | 详情 | 详情 | |
(VII) | 38115 | 3-[(chlorocarbonyl)oxy]-1-propene | 2937-50-0 | C4H5ClO2 | 详情 | 详情 |
(VIII) | 62875 | allyl 5-[3-(5-{[(allyloxy)carbonyl]amino}-4-{[(2S,4R)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-hydroxypyrrolidinyl]carbonyl}-2-methoxyphenoxy)propoxy]-2-{[(2S,4R)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-hydroxypyrrolidinyl]carbonyl}-4-metho | C49H76N4O14Si2 | 详情 | 详情 | |
(IX) | 62876 | allyl 5-[3-(5-{[(allyloxy)carbonyl]amino}-4-{[(2S)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-oxopyrrolidinyl]carbonyl}-2-methoxyphenoxy)propoxy]-2-{[(2S)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-oxopyrrolidinyl]carbonyl}-4-methoxyphenylcarbam | C49H72N4O14Si2 | 详情 | 详情 | |
(X) | 30484 | Methyl(triphenyl)phosphonium bromide | 1779-49-3 | C19H18BrP | 详情 | 详情 |
(XI) | 62877 | allyl 5-[3-(5-{[(allyloxy)carbonyl]amino}-4-{[(2S)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-methylenepyrrolidinyl]carbonyl}-2-methoxyphenoxy)propoxy]-2-{[(2S)-2-({[tert-butyl(dimethyl)silyl]oxy}methyl)-4-methylenepyrrolidinyl]carbonyl}-4-methoxy | C51H76N4O12Si2 | 详情 | 详情 |