反应详情

温度

90 °C

To a 2 L Erlenmeyer flask were added 4-fluoro-3-methyl-benzene-1,2-diamine.HCl (46.32 g, 262.3 mmol), Na2S2O5 (64.82 g, 341.0 mmol), and 4-methyl-2-[3-(1-methyl-piperidin-4-yl)-propylamino]-pyrimidine-5-carbaldehyde (72.5 g, 262.3 mmol) in DMF (725 mL). To the resultant mixture was then added triethylamine (36.6 mL, 262.3 mmol), and the reaction was warmed on a hot plate with stirring to 90° C. and held at this temperature for 2 hours. The resultant mixture was then concentrated to near dryness and partitioned between dichloromethane (1 L) and 1 N NaOH (1 L). After separation of the layers, the aqueous layer was extracted a second time with dichloromethane (1 L). The combined organic layers were then washed with saturated aqueous NaHCO3 (1.6 L). The organics were then extracted with a 1 M mono/dibasic phosphate buffer (pH 5.62, 1.23 L). The aqueous layer was then basified with 50% NaOH (80 mL) to pH 10.8. The resultant heterogeneous layer was then extracted with dichloromethane (1.5 L and 500 mL), and the combined organics were concentrated to yield the title compound.

1. concentrationThe resultant mixture was then concentrated
2. custompartitioned between dichloromethane (1 L) and 1 N NaOH (1 L)
3. customAfter separation of the layers
4. extractionthe aqueous layer was extracted a second time with dichloromethane (1 L)
5. washThe combined organic layers were then washed with saturated aqueous NaHCO3 (1.6 L)
6. extractionThe organics were then extracted with a 1 M mono/dibasic phosphate buffer (pH 5.62, 1.23 L)
7. extractionThe resultant heterogeneous layer was then extracted with dichloromethane (1.5 L and 500 mL)
8. concentrationthe combined organics were concentrated