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【结 构 式】 
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【分子编号】32859 【品名】benzyl 4-aminobutyl(3-[[(benzyloxy)carbonyl]amino]propyl)carbamate 【CA登记号】 |
【 分 子 式 】C23H31N3O4 【 分 子 量 】413.51696 【元素组成】C 66.81% H 7.56% N 10.16% O 15.48% |
合成路线1
该中间体在本合成路线中的序号：(IX)A new synthesis of (-)-15-deoxyspergualin has been reported: The hydrolysis of 7-bromoheptanenitrile (I) with HCl gives the corresponding amide (II), which by reaction with sodium azide yields 7-azidoheptanamide (III). The condensation of (III) with 2-hydroxy-2-methoxyacetic acid methyl ester (IV) affords the alpha-hydroxyglycine derivative (V), which is condensed with 1(S)-(2-naphthyl)ethanol (VI) by means of SO2Cl2 and triethylamine in dichloromethane providing the diastereomeric mixture (VII). Hydrolysis of the ester group of (VII) with NaOH yields the corresponding free acid (VIII), which is condensed with the diprotected triamine (IX) by means of DCC and HOBt in dichloromethane affording a diastereomeric mixture of diamides. This mixture is separated by flash chromatography giving the desired diastereomer (X). The condensation of (X) with the protected isothiourea (XI) by means of triphenylphosphine in THF/water provides the proteted guanidino derivative (XII), which is finally deprotected by hydrogenation with H2 over Pd/C in methanol/acetic acid.
| 【1】 Durand, P.; et al.; (-)-15-Deoxyspergualin: A new and efficient enantioselective synthesis which allows the definitive assignment of the absolute configuration. J Org Chem 1998, 63, 26, 9723. |
| 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) | 32852 | 7-bromoheptanenitrile | 20965-27-9 | C7H12BrN | 详情 | 详情 |
| (II) | 32853 | 7-bromoheptanamide | C7H14BrNO | 详情 | 详情 | |
| (III) | 32854 | 7-azidoheptanamide | C7H14N4O | 详情 | 详情 | |
| (IV) | 22764 | methyl 2-hydroxy-2-methoxyacetate | 19757-97-2 | C4H8O4 | 详情 | 详情 |
| (V) | 32855 | methyl 2-[(7-azidoheptanoyl)amino]-2-hydroxyacetate | C10H18N4O4 | 详情 | 详情 | |
| (VI) | 32856 | (1S)-1-(2-naphthyl)-1-ethanol; 1(S)-(2-naphthyl)ethanol | 7228-47-9 | C12H12O | 详情 | 详情 |
| (VII) | 32857 | methyl 2-[(7-azidoheptanoyl)amino]-2-[[(1S)-1-(2-naphthyl)ethyl]oxy]acetate | C22H28N4O4 | 详情 | 详情 | |
| (VIII) | 32858 | 2-[(7-azidoheptanoyl)amino]-2-[[(1S)-1-(2-naphthyl)ethyl]oxy]acetic acid | C21H26N4O4 | 详情 | 详情 | |
| (IX) | 32859 | benzyl 4-aminobutyl(3-[[(benzyloxy)carbonyl]amino]propyl)carbamate | C23H31N3O4 | 详情 | 详情 | |
| (X) | 32860 | benzyl 4-[((2S)-2-[(7-azidoheptanoyl)amino]-2-[[(1S)-1-(2-naphthyl)ethyl]oxy]ethanoyl)amino]butyl(3-[[(benzyloxy)carbonyl]amino]propyl)carbamate | C44H55N7O7 | 详情 | 详情 | |
| (XI) | 32861 | benzyl (E)-[[(benzyloxy)carbonyl]amino](methylsulfanyl)methylidenecarbamate | C18H18N2O4S | 详情 | 详情 | |
| (XII) | 32862 | benzyl (7S,17Z)-17-[[(benzyloxy)carbonyl]amino]-7-[[(1S)-1-(2-naphthyl)ethyl]oxy]-6,9,19-trioxo-21-phenyl-20-oxa-5,8,16,18-tetraaza-17-henicosen-1-yl(3-[[(benzyloxy)carbonyl]amino]propyl)carbamate | C61H71N7O11 | 详情 | 详情 |
合成路线2
该中间体在本合成路线中的序号：(IX)The hydrolysis of 7-bromoheptanenitrile (I) with HCl gives the corresponding amide (II), which is treated with Na-N3 in hot DMSO to yield 7-azidoheptanamide (III) (1). The condensation of (III) with 2-hydroxy-2-methoxyacetic acid methyl ester (IV) in hot dichloromethane affords the alpha-hydroxyglycine (V), which is treated with SOCl2 in the same solvent to provide the alpha-chloroglycine (VI). The reaction of (VI) with benzyl alcohol and TEA in dichloromethane furnishes the benzyloxy derivative (VII), which is hydrolyzed at the ester group by means of NaOH in DME to give the carboxylic acid (VIII). The condensation of (VIII) with N1,N4-bis(benzyloxycarbonyl)spermidine (IX) by means of DCC and HOBt in dichloromethane yields the corresponding amide (X), which is reduced at the terminal azido group by means of PPh3 in THF/water, affording the expected primary amine (XI). The condensation of (XI) with the protected isothiourea (XII) in THF affords the protected guanidine derivative (XIII), which is finally deprotected by hydrogenolysis with H2 over Pd(OH)2 in methanol/acetic acid to provide the target compound.
| 【1】 Durand, P.; et al.; A new efficient synthesis of the immunosuppressive agent (±)-15-deoxyspergualin. Tetrahedron 2001, 57, 14, 2757. |
| 【2】 Durand, P.; et al.; (-)-15-Deoxyspergualin: A new and efficient enantioselective synthesis which allows the definitive assignment of the absolute configuration. J Org Chem 1998, 63, 26, 9723. |
| 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) | 32852 | 7-bromoheptanenitrile | 20965-27-9 | C7H12BrN | 详情 | 详情 |
| (II) | 32853 | 7-bromoheptanamide | C7H14BrNO | 详情 | 详情 | |
| (III) | 32854 | 7-azidoheptanamide | C7H14N4O | 详情 | 详情 | |
| (IV) | 22764 | methyl 2-hydroxy-2-methoxyacetate | 19757-97-2 | C4H8O4 | 详情 | 详情 |
| (V) | 32855 | methyl 2-[(7-azidoheptanoyl)amino]-2-hydroxyacetate | C10H18N4O4 | 详情 | 详情 | |
| (VI) | 55499 | methyl 2-[(7-azidoheptanoyl)amino]-2-chloroacetate | C10H17ClN4O3 | 详情 | 详情 | |
| (VII) | 55500 | methyl 2-[(7-azidoheptanoyl)amino]-2-(benzyloxy)acetate | C17H24N4O4 | 详情 | 详情 | |
| (VIII) | 55501 | 2-[(7-azidoheptanoyl)amino]-2-(benzyloxy)acetic acid | C16H22N4O4 | 详情 | 详情 | |
| (IX) | 32859 | benzyl 4-aminobutyl(3-[[(benzyloxy)carbonyl]amino]propyl)carbamate | C23H31N3O4 | 详情 | 详情 | |
| (X) | 55502 | benzyl 4-{[2-[(7-azidoheptanoyl)amino]-2-(benzyloxy)acetyl]amino}butyl(3-{[(benzyloxy)carbonyl]amino}propyl)carbamate | C39H51N7O7 | 详情 | 详情 | |
| (XI) | 55503 | benzyl 4-{[2-[(7-aminoheptanoyl)amino]-2-(benzyloxy)acetyl]amino}butyl(3-{[(benzyloxy)carbonyl]amino}propyl)carbamate | C39H53N5O7 | 详情 | 详情 | |
| (XII) | 32861 | benzyl (E)-[[(benzyloxy)carbonyl]amino](methylsulfanyl)methylidenecarbamate | C18H18N2O4S | 详情 | 详情 | |
| (XIII) | 55504 | benzyl (Z)-7-(benzyloxy)-17-{[(benzyloxy)carbonyl]amino}-6,9,19-trioxo-21-phenyl-20-oxa-5,8,16,18-tetraaza-17-henicosen-1-yl(3-{[(benzyloxy)carbonyl]amino}propyl)carbamate | C56H67N7O11 | 详情 | 详情 |