L-Phenylalanine, N-[(1,1-dimethylethoxy)carbonyl]- → L-Phenylalanine

The 5′-O—[N-(aminoacyl)sulfamoyl]adenosine inhibitor Phe-SA (FIG. 19b) was synthesized as follows: to a solution of alcohol (7 g, 17.03 mmol, 1.0 eq) in DMAC (70 mL) at 0° C. was added DIEA (10.62 mL, 59.61 mmol, 4.0 eq) and sulfamoyl chloride (4 eq) and the reaction mixture was stirred at room temperature for 15 h. The reaction mixture was diluted with ethyl acetate (300 mL) and washed with water (4×50 mL). The organic layer was dried over MgSO4, evaporated and purified by column chromatography (DCM to 20% MeOH in DCM) to give the activated sulfamate (4.5 g, 9.18 mmol, 54% yield) To a solution of sulfamate (2.0 g, 4.07 mmole, 1 eq), DCC (0.841 g, 4.07 mmol, 1 eq), DMAP (050 g, 4.07 mmol, 1.0 eq) in DCM (45 mL) was added Boc-Phe-OH (1.1 g, 4.07 mmol, 1 eq) and the reaction mixture was stirred at room temperature for 10 h. The reaction mixture was diluted with ethyl acetate (450 mL), washed with saturated aqueous NaHCO3, water, brine, dried over MgSO4, and evaporated. The crude product was dissolved in MeOH/n-butylamine (30 mL/30 mL) and stirred at room temperature for 3 h. The solvents were evaporated and the crude product was purified by flash chromatography (EtOAc to 10% MeOH/EtOAc) to give the Phe-SA inhibitor (0.90 g, 1.4 mmol, 35% yield)

1. washwashed with saturated aqueous NaHCO3, water, brine
2. dry with materialdried over MgSO4
3. customevaporated
4. dissolutionThe crude product was dissolved in MeOH/n-butylamine (30 mL/30 mL)
5. stirringstirred at room temperature for 3 h
6. customThe solvents were evaporated
7. customthe crude product was purified by flash chromatography (EtOAc to 10% MeOH/EtOAc)

ORD record

ord-de5ca147591c491b99589b9c97b6f148

Source dataset

uspto-grants-2014_07

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08778631B2