Diisopropylethylamine → (5-Bromo-[1,2,4]triazolo[1,5-a]pyrazin-8-yl)-[4-(1-isopropylpiperidin-4-yl)phenyl]amine

N,N-Diisopropylethylamine (200 μL, 1.2 mmol) is added to a mixture of 4-(1-isopropylpiperidin-4-yl)phenylamine (220 mg, 1.0 mmol) and 5,8-dibromo-[1,2,4]triazolo[1,5-a]pyrazine (280 mg, 1.0 mmol) in iPrOH (5 mL) and heated at reflux for 48 h. The mixture is cooled and the solvent evaporated under reduced pressure to afford an orange-brown solid. This is partitioned between DCM (50 mL) and water (20 mL) and the layers are separated. The organic phase is washed with citric acid (10% aq., 3×25 mL). The combined washings are extracted with DCM (25 mL) and then made basic by addition of NaHCO3 (s). The mixture is extracted with DCM (3×25 mL) and the combined extracts dried over MgSO4 and evaporated. The crude product was purified by chromatography on silica gel, eluting with 5%-10% MeOH in DCM to afford the desired compound, contaminated with the starting aniline. This was recrystallised from MeOH to afford the pure title compound (110 mg).

1. temperatureheated
2. temperatureat reflux for 48 h
3. temperatureThe mixture is cooled
4. customthe solvent evaporated under reduced pressure
5. customto afford an orange-brown solid
6. customThis is partitioned between DCM (50 mL) and water (20 mL)
7. customthe layers are separated
8. washThe organic phase is washed with citric acid (10% aq., 3×25 mL)
9. extractionThe combined washings are extracted with DCM (25 mL)
10. additionmade basic by addition of NaHCO3 (s)
11. extractionThe mixture is extracted with DCM (3×25 mL)
12. dry with materialthe combined extracts dried over MgSO4
13. customevaporated
14. customThe crude product was purified by chromatography on silica gel
15. washeluting with 5%-10% MeOH in DCM

ORD record

ord-54fc59c1e7734eaa913bb1ff1fa7bf79

Source dataset

uspto-grants-2011_03

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07915256B2