Isopropylamine → HCID 118159347, compound

Temperature

0 °C

To a solution of 2,3-dichloropyrido[3,4-b]pyrazine (2.5 g, 12.50 mmol) and DIPEA (6.53 mL, 37.5 mmol) in DCM (25 mL) was added propan-2-amine (1.065 mL, 12.50 mmol) at 0° C. The mixture was stirred at 0° C. for 30 min, warmed slowly to 23° C., and stirred for 12 h. The crude mixture was partitioned between EtOAc (100 mL) and saturated aqueous NH4Cl (100 mL). The layers were separated and the aqueous phase was washed with EtOAc (4×100 mL). The organic extracts were combined, washed with brine (50 mL), dried over Na2SO4, filtered, rinsed with EtOAc, and dried in vacuo. The crude material was dissolved in toluene (5 mL) and purified via medium pressure chromatography using a gradient eluant of 50% to 75% EtOAc in heptane on a 80 g silica gel column (Single Step™) to give the title compound (1.828 g, 65.7%) as a yellow-orange solid. 1H NMR (400 MHz, DMSO-d6) δ ppm 1.28 (d, J=6.6 Hz, 6H), 4.39-4.49 (m, 1H), 7.49 (dd, J=5.8, 0.8 Hz, 1H), 7.73 (d, J=7.8 Hz, 1H), 8.52 (d, J=5.6 Hz, 1H), 8.95 (d, J=0.8 Hz, 1H); ESI-MS m/z [M+H]+ 223.1.

1. temperaturewarmed slowly to 23° C.
2. stirringstirred for 12 h
3. customThe crude mixture was partitioned between EtOAc (100 mL) and saturated aqueous NH4Cl (100 mL)
4. customThe layers were separated
5. washthe aqueous phase was washed with EtOAc (4×100 mL)
6. washwashed with brine (50 mL)
7. dry with materialdried over Na2SO4
8. filtrationfiltered
9. washrinsed with EtOAc
10. customdried in vacuo
11. dissolutionThe crude material was dissolved in toluene (5 mL)
12. custompurified via medium pressure chromatography

ORD record

ord-4d2321cc5bcd48239ebf73c26eac423d

Source dataset

uspto-grants-2015_11

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09181249B2