Diisopropylethylamine → (R)-5-(6-cyclohexyl-1-(hydroxyamino)-1-oxohexan-3-yl)-N-propyl-1,2,4-oxadiazole-3-carboxamide

A solution of (3R)-6-cyclohexyl-3-{3-[(propylamino)carbonyl]-1,2,4-oxadiazol-5-yl}hexanoic acid (Preparation 9) (66 mg, 0.18 mmol) and N,N-diisopropylethylamine (31 μl, 0.18 mmol) in N-methyl-2-pyrrolidinone (3 ml) was treated with O-(7-azabenzotriazol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (102 mg, 0.27 mmol) and the resulting mixture was stirred at room temperature under a nitrogen atmosphere for 1 hour. N,N-diisopropylethylamine (93 μl, 0.54 mmol) was then added, followed by hydroxylamine hydrochloride (37.5 mg, 0.54 mmol) and the mixture was stirred at room temperature for 18 hours. The mixture was partitioned between ethyl acetate and pH 7 aqueous buffer. The combined organic layers were washed sequentially with aqueous citric acid solution (5% w/v) and brine, dried over anhydrous sodium sulphate, filtered and the solvent removed under reduced pressure. The residue was purified by column chromatography on silica gel eluting with a gradient system of dichloromethane:ethyl acetate (90:10) gradually changing to dichloromethane:ethyl acetate (0:100) then to dichloromethane:methanol (95:5) to afford the title compound as an oil (31 mg).

1. stirringthe mixture was stirred at room temperature for 18 hours
2. customThe mixture was partitioned between ethyl acetate and pH 7 aqueous buffer
3. washThe combined organic layers were washed sequentially with aqueous citric acid solution (5% w/v) and brine
4. dry with materialdried over anhydrous sodium sulphate
5. filtrationfiltered
6. customthe solvent removed under reduced pressure
7. customThe residue was purified by column chromatography on silica gel eluting with a gradient system of dichloromethane:ethyl acetate (90:10)

ORD record

ord-972083d9f9f14d8d9de4d5a6ebadcf96

Source dataset

uspto-grants-2005_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06897306B2