反应 #456986

反应方程式

HCl

ethyl N-((S)-2-(5-(((1,2-dihydro-3-methyl-1-oxobenzo(f)quinazolin-9-yl)methyl)amino)-1-oxo-2-isoindolinyl)-4-(ethoxycarbonyl)butanoyl)-L-phenylalaninate

NaOH

→

N-((S)-4-carboxy-2-(5-(((1,2-dihydro-3-methyl-1-oxobenzo(f)quinazolin-9-yl)methyl)amino)-1-oxo-2-isoindolinyl)butanoyl)-L-phenylalanine

收率 40.0%

溶剂

EtOH

反应条件

后处理

1. 1
   其他To a 100 mL 3-necked flask equipped with a magnetic stirrer and a nitrogen inlet
2. 2
   其他A white precipitate resulted which
3. 3
   其他was separated by centrifugation
4. 4
   其他The crude product was purified by semi-preparative reverse phase HPLC (C18, 75:25:0.1 H2O:MeCN:TFA)
5. 5
   workup.ADDITIONFractions containing pure product (k'=1.93 by analytical HPLC
6. 6
   浓缩concentrated in vacuo to dryness
7. 7
   workup.DISSOLUTIONThe residue was dissolved in 15 mL of 0.1N aqueous NaOH
8. 8
   workup.ADDITIONthe solution was adjusted to pH 3.0 by addition of 1N HCl
9. 9
   其他The resulting precipitate was collected by centrifugation
10. 10
    洗涤washed with four cycles of aqueous suspension-centrifugation-decantation

实验过程

To a 100 mL 3-necked flask equipped with a magnetic stirrer and a nitrogen inlet were added 0.90 g of ethyl N-((S)-2-(5-(((1,2-dihydro-3-methyl-1-oxobenzo(f)quinazolin-9-yl)methyl)amino)-1-oxo-2-isoindolinyl)-4-(ethoxycarbonyl)butanoyl)-L-phenylalaninate, 3 mL of EtOH and 10 mL of 0.2N aqueous NaOH. The solution was stirred at RT under nitrogen for 2 h and was acidified to pH 3.0 by addition of 1N HCl. A white precipitate resulted which was separated by centrifugation. Analysis of this material by analytical HPLC (C18, 70:30:0.10 H2O:MeCN:TFA) indicated a major component at K'=1.93 (90%) and a minor component at k'=2.41. The crude product was purified by semi-preparative reverse phase HPLC (C18, 75:25:0.1 H2O:MeCN:TFA). Fractions containing pure product (k'=1.93 by analytical HPLC using above conditions) were combined and concentrated in vacuo to dryness. The residue was dissolved in 15 mL of 0.1N aqueous NaOH and the solution was adjusted to pH 3.0 by addition of 1N HCl. The resulting precipitate was collected by centrifugation, washed with four cycles of aqueous suspension-centrifugation-decantation, and lyophilized to afford 0.035 g (40%) of N-((S)-4-carboxy-2-(5-(((1,2-dihydro-3-methyl-1-oxobenzo(f)quinazolin-9-yl)methyl)amino)-1-oxo-2-isoindolinyl)butanoyl)-L-phenylalanine as a white powder, m.p. 180° C.

来源