反应详情

温度

21 °C

To a reactor was charged, 3-Amino-6-bromo-N-(pyridin-3-yl)pyrazine-2-carboxamide (1580 g), tert-butyl (3-methoxypropyl){3-[4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)phenyl]propyl}carbamate (2778 g) 1-butanol (23.7 L), potassium phosphate, tribasic, N-hydrate (2740 g) and water (1.58 L). The contents were stirred under nitrogen at ambient (21° C.). In a second reactor was made up a solution of 3-(di-tert-butylphosphonium)propane sulphonate (DTBPPS) (83.04 g); sodium tetrachloropalladate (45.52 g) and water (1.58 L). The catalyst/ligand solution was poured into the reaction; the reaction was inerted and heated up to 80° C. The reaction was stirred for 2 hours at 80° C. The batch was cooled to 60° C. and water (22.1 L) was added. The contents washed with water at 60° C. The organic layer and interface were filtered through perlite (500 g) made up with 1-Butanol (3.95 L). The organic liquors were recharged to the vessel and washed with water (11.1 L) at 60° C. The organic liquor was washed with 10% w/v aqueous sodium chloride (11.2 L) at 60° C. The organic liquors were heated up to 60° C. and distilled under vacuum to ˜10 relative volumes. The batch was cooled to 20° C. and left to stir for 16 hours under nitrogen. The contents were filtered and washed with 1-Butanol (4 L×2). The yellow free flowing solid was discharged and dried in vacuum oven at 40° C. overnight (tert-butyl (3-{4-[5-amino-6-(pyridin-3-ylcarbamoyl)pyrazin-2-yl]phenyl}propyl)(3-methoxypropyl)carbamate (2428 g)).

1. additionTo a reactor was charged
2. customIn a second reactor was made up
3. additionThe catalyst/ligand solution was poured into the reaction
4. temperatureheated up to 80° C
5. stirringThe reaction was stirred for 2 hours at 80° C
6. temperatureThe batch was cooled to 60° C.
7. washThe contents washed with water at 60° C
8. filtrationThe organic layer and interface were filtered through perlite (500 g)
9. washwashed with water (11.1 L) at 60° C
10. washThe organic liquor was washed with 10% w/v aqueous sodium chloride (11.2 L) at 60° C
11. temperatureThe organic liquors were heated up to 60° C.
12. distillationdistilled under vacuum to ˜10 relative volumes
13. temperatureThe batch was cooled to 20° C.
14. waitleft
15. stirringto stir for 16 hours under nitrogen
16. filtrationThe contents were filtered
17. washwashed with 1-Butanol (4 L×2)
18. dry with materialdried in vacuum oven at 40° C. overnight (tert-butyl (3-{4-[5-amino-6-(pyridin-3-ylcarbamoyl)pyrazin-2-yl]phenyl}propyl)(3-methoxypropyl)carbamate (2428 g))