反应详情

To a solution of 3-[3-(3-methylimidazolidine-2,5-dione-1-ylmethyl)phenyl]-5-iso-butyl-N-tert-butylthiophene-2-sulfonamide (42.1 mg, 0.088 mmol; see step (a)) in CH2Cl2 (2 mL) was added BCl3 (0.6 mL, 1.0 M in hexane) and the reaction mixture was stirred for 1 h at ambient temperature. The reaction mixture was concentrated in vacuo. Water (5 mL) was added to the residue and this was then extracted with EtOAc. The combined organic phase was washed with water, and brine, dried (over anhydrous MgSO4) and concentrated in vacuo. To the crude product dissolved in pyridine (1.5 mL) was added pyrrolidinopyridine (26.1 mg, 0.176 mmol) and butyl chloroformate (112.0 μL, 0.88 mmol) and the reaction mixture was stirred overnight. Citric acid (3 mL, 10% aq) was added to the reaction mixture, which was then extracted with EtOAc, dried (over anhydrous MgSO4), concentrated in vacuo, and the residue purified by flash chromatography using MeOH:CH2Cl2 (3:97) as eluent and then with LCMS (30-100% CH3CN in water) to give the title compound in 80% yield, over two steps, (36.6 mg, 0.702 mmol).

1. concentrationThe reaction mixture was concentrated in vacuo
2. additionWater (5 mL) was added to the residue
3. extractionthis was then extracted with EtOAc
4. washThe combined organic phase was washed with water, and brine
5. dry with materialdried (over anhydrous MgSO4)
6. concentrationconcentrated in vacuo
7. dissolutionTo the crude product dissolved in pyridine (1.5 mL)
8. stirringthe reaction mixture was stirred overnight
9. extractionwas then extracted with EtOAc
10. dry with materialdried (over anhydrous MgSO4)
11. concentrationconcentrated in vacuo
12. customthe residue purified by flash chromatography