Dimethylformamide → (S)-3-((5-((6-Bromobenzo[d]thiazol-2-yl)methyl)-1,3,4-oxadiazol-2-yl)amino)pyrrolidin-2-one

Temperature

35 °C

To a solution of Compound 51a (145 mg, 0.47 mmol) in DMF (4 mL) was added DIEA (0.243 mL, 1.39 mmol) followed by (S)-3-aminopyrrolidin-2-one, HCl (70 mg, 0.51 mmol). To the stirring solution was added BOP (247 mg, 0.56 mmol) and the reaction mixture stirred at 35° C. for 18 h. The reaction mixture was diluted with EtOAc and the solution washed with saturated NH4Cl. The aqueous portion was washed with EtOAc, and the combined organic extracts washed with brine. The organic portion was dried (Na2SO4), filtered and concentrated under reduced pressure then the residue purified on silica gel chromatography eluting with 0.5 to 12% MeOH to give Compound 51b (92 mg, 50% yield) as a light orange solid. LCMS=0.75 min using analytical method (M), 396.0 (M+H). 1H NMR (400 MHz CDCl3 containing CD3OD) δ 8.02 (d, J=1.8 Hz, 1H), 7.82 (d, J=8.8 Hz, 1H), 7.58 (dd, J=8.7, 1.9 Hz, 1H), 4.26 (dd, J=10.4, 8.4 Hz, 1H), 3.43-3.38 (m, 1H), 2.68 (dddd, J=12.6, 8.3, 6.1, 2.0 Hz, 1H), 2.18-1.96 (m, 1H).

1. washthe solution washed with saturated NH4Cl
2. washThe aqueous portion was washed with EtOAc
3. washthe combined organic extracts washed with brine
4. dry with materialThe organic portion was dried (Na2SO4)
5. filtrationfiltered
6. concentrationconcentrated under reduced pressure
7. customthe residue purified on silica gel chromatography
8. washeluting with 0.5 to 12% MeOH

ORD record

ord-e5fb79b413e245e0adeea13c36034b38

Source dataset

uspto-grants-2015_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09169240B2