反应详情

To a solution of 2-{2-[{2-[2-(dimethylamino)ethoxy]pyridin-3-yl}oxy]ethoxy}-3-[(2R)-2-methylpiperazin-1-yl]pyrazine (from Example 1; 0.48 g, 1.19 mmol) in 1,2-dichloroethane (4 mL) was added sodium triacetoxyborohydride (1.3 g, 6.2 mmol) and 37% aqueous formaldehyde (0.072 g, 2.4 mmol), the slightly exothermic reaction was stirred at ambient temperature overnight. Water was added and the mixture was made basic (pH>13) by addition of 8 M NaOH. After being stirred for five minutes, the phases were separated and the aqueous phase was extracted twice with CHCl3. The combined organic phases were dried (MgSO4) and the solvent was removed under reduced pressure. The resulting oil was chromatographed on a column of silica (80 mm, i.d.=30 mm) with CHCl3/MeOH/NH4OH (95:5:0.2; 100 mL, followed by 90:10:0.2) as eluent to give 0.33 (67%) of the title compound as a colorless oil. HRMS m/z calcd for C21H32N6O3 (M)+ 416.2536. found 416.2523.

1. customthe slightly exothermic reaction
2. stirringAfter being stirred for five minutes
3. customthe phases were separated
4. extractionthe aqueous phase was extracted twice with CHCl3
5. dry with materialThe combined organic phases were dried (MgSO4)
6. customthe solvent was removed under reduced pressure
7. customThe resulting oil was chromatographed on a column of silica (80 mm, i.d.=30 mm) with CHCl3/MeOH/NH4OH (95:5:0.2; 100 mL, followed by 90:10:0.2) as eluent