Trifluoroacetic acid → 6-[2-(2-Oxopiperazin-1-yl)ethyl]pyridine-3-carbonitrile

TEA (1 eq) was added dropwise to a solution of tert-Butyl (2-{[2-(5-cyanopyridin-2-yl)ethyl]amino}ethyl)carbamate (1 eq) and chloroacetyl chloride (1 eq) in 200 mL of DCM at 0° C. The mixture was stirred at room temperature for 30 minutes and washed with water and brine, dried over anhydrous Na2SO4 and condensed under vacuum. The resulting solid (1.0 g, 2.7 mmol) was added to the mixture of 10 mL TFA and 10 mL of DCM and stirred at RT for 1 hour then concentrated by vacuum. The residue was re-dissolved in CH3CN, K2CO3 was added and the mixture was stirred at RT for 2 hours. The mixture was poured into water and extracted with EtOAc twice. The combined organic layers were concentrated and the residue was purified by flash chromatography (DCM:MeOH=10:1) to afford the title compound 1H-NMR (400 MHz, CDCl3) δ ppm 8.74 (d, J=1.6 Hz, 1H), 7.81-7.83 (m, 1H), 7.31 (d, J=8.0 Hz, 1H), 3.71 (t, J=7.2 Hz, 2H), 3.42 (d, J=7.2 Hz, 2H), 3.24 (t, J=5.6 Hz, 2H), 3.09 (t, J=7.2 Hz, 2H), 2.98 (t, J=5.6 Hz, 2H).

1. washwashed with water and brine
2. dry with materialdried over anhydrous Na2SO4 and condensed under vacuum
3. stirringstirred at RT for 1 hour
4. concentrationthen concentrated by vacuum
5. dissolutionThe residue was re-dissolved in CH3CN
6. additionK2CO3 was added
7. stirringthe mixture was stirred at RT for 2 hours
8. additionThe mixture was poured into water
9. extractionextracted with EtOAc twice
10. concentrationThe combined organic layers were concentrated
11. customthe residue was purified by flash chromatography (DCM:MeOH=10:1)

ORD record

ord-26792eb4f3b44751b79f7e7510341d7b

Source dataset

uspto-grants-2015_04

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08999990B2