反应详情

To a stirred solution of 2.92 g (8.61 mmol) of the product of Step D in 40 mL of methylene chloride was added 2.31 g (12.05 mmol) of 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride, 1.26 g (10.33 mmol)of 4-dimethylaminopyridine, and 1.89 g (9.47 mmol) of 4-iso-propylbenzenesulfonamide. The reaction mixture was stirred overnight and after TLC analysis (80:15:1 chloroform/methanol/ammonium hydroxide) was poured into 1N HCl and extracted with ethyl acetate. The extract was washed with brine, dried over magnesium sulfate, filtered, and evaporated in vacuo. The residue was partially purified with silica gel flash chromatography eluting first with 40% ethyl acetate-hexane and then with 3% methanol-methylene chloride to flush the column. All of the product fractions were contaminated and were chromatographed. The 3.86 g of semi-purified material was dissolved in 15 mL of acetonitrile and 15 mL of water and filtered through a 0.45 μM membrane filter. The compound was purified using a Waters Delta Prep 3000 HPLC by applying the filtered solution to an M1000 Prep-Pak module containing a 47×300 mm 15 mM DeltaPak C18 column and eluting at 50 mL/min first using 50% A (95-5 acetonitile-water) and 50% B (95-5 water-acetonitrile) with 0.1% TFA for 15 minutes and then 70% A (95-5 acetonitile-water) and 30% B (95-5 water-acetonitrile) both with 0.1% TFA. The column effluent was monitored simultaneously at 210 and 277 nM with a Waters model 490 UV-visible detector and the purified fractions were combined in a round bottom flask and concentated in vacuo to afford 1.45 g (38%) of the title compound as an amorphous solid.

1. extractionextracted with ethyl acetate
2. washThe extract was washed with brine
3. dry with materialdried over magnesium sulfate
4. filtrationfiltered
5. customevaporated in vacuo
6. customThe residue was partially purified with silica gel flash chromatography
7. washeluting first with 40% ethyl acetate-hexane
8. customwith 3% methanol-methylene chloride to flush the column
9. customwere chromatographed
10. dissolutionThe 3.86 g of semi-purified material was dissolved in 15 mL of acetonitrile
11. filtration15 mL of water and filtered through a 0.45 μM membrane
12. filtrationfilter
13. customThe compound was purified
14. additioncontaining a 47×300 mm 15 mM DeltaPak C18 column
15. washeluting at 50 mL/min
16. customfor 15 minutes
17. customthe purified fractions were combined in a round bottom flask