Potassium Carbonate → (R)-2-Chloro-3-(2-methylpiperazin-1-YL)pyrazine

Temperature

110 °C

A mixture of the product obtained in Step 1 above, 2,3-dichloropyrazine (154 g, 1.00 mol) and K2CO3 (160 g, 1.20 mol) in DMF (1 L) was heated at 110° C. for 20 h with vigorous stirring. (TLC monitoring system: CHCl3: EtOH (20:1); silica). The mixture was cooled and poured slowly into water (6 L) with stirring. The solid was collected, washed with water, dried, dissolved in CHCl3 (1 L), diluted with n-heptane (1 L), and filtered through SiO2. Solvents were evaporated off. The resulting oil was dried under vacuum (3 mm/50° C., 30 min) to remove the DMF. The oil was dissolved in hot ethanol (1 L), and HCl (10% aqueous solution, 300 mL) was added slowly. Trityl carbinol began to crystallize out after 10 min. After 30 min, the formed trityl carbinol was filtered off and the ethanol was evaporated. The aqueous solution was extracted by ether (2×200 mL) and made basic by addition of K2CO3 to pH 12. The alkaline layer was extracted with CHCl3 (3×200 mL). The combined organic layers were dried (K2CO3) and concentrated to give 140 g (66%) of the title compound.

1. temperatureThe mixture was cooled
2. customThe solid was collected
3. washwashed with water
4. customdried
5. dissolutiondissolved in CHCl3 (1 L)
6. additiondiluted with n-heptane (1 L)
7. filtrationfiltered through SiO2
8. customSolvents were evaporated off
9. customThe resulting oil was dried under vacuum (3 mm/50° C., 30 min)
10. customto remove the DMF
11. dissolutionThe oil was dissolved in hot ethanol (1 L)
12. additionHCl (10% aqueous solution, 300 mL) was added slowly
13. customto crystallize out after 10 min
14. filtrationthe formed trityl carbinol was filtered off
15. customthe ethanol was evaporated
16. extractionThe aqueous solution was extracted by ether (2×200 mL)
17. additionmade basic by addition of K2CO3 to pH 12
18. extractionThe alkaline layer was extracted with CHCl3 (3×200 mL)
19. dry with materialThe combined organic layers were dried (K2CO3)
20. concentrationconcentrated

ORD record

ord-831f8982e12643a3be706b60f8174cff

Source dataset

uspto-grants-2002_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US06465467B1