反应详情

温度

90 °C

To a 2 L Erlenmeyer flask were added 3,5-dimethyl-benzene-1,2-diamine.2HCl (54.85 g, 262.3 mmol) and Na2S2O5 (64.82 g, 341.0 mmol), as well as 4-methyl-2-[3-(1-methyl-piperidin-4-yl)-propylamino]-pyrimidine-5-carbaldehyde (prepared as in Example 3 above) (72.5 g, 262.3 mmol) in DMF (725 mL). After addition of triethylamine (73.1 mL, 524.6 mmol), the resultant mixture 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 (0.7 L) and 1 N NaOH (1 L). The resultant mixture was stirred for 1 hour and then filtered to isolate the voluminous solid which had formed. The solids were dried and then partitioned between chloroform (700 mL) and saturated aqueous NaHCO3 (700 mL). The layers were separated, the organic layer was dried over sodium sulfate and concentrated to a residue. The residue was recrystallized in hot heptane/ethyl acetate (1.8:1, 840 mL total volume) with initial hot filtration (˜1 g of oily residues removed) and final filter cake washing with heptane/ethyl acetate (3:1, 250 mL total volume) to yield the title compound as a crystalline solid.

1. concentrationThe resultant mixture was then concentrated
2. custompartitioned between dichloromethane (0.7 L) and 1 N NaOH (1 L)
3. stirringThe resultant mixture was stirred for 1 hour
4. filtrationfiltered
5. customto isolate the voluminous solid which
6. customhad formed
7. customThe solids were dried
8. custompartitioned between chloroform (700 mL) and saturated aqueous NaHCO3 (700 mL)
9. customThe layers were separated
10. dry with materialthe organic layer was dried over sodium sulfate
11. concentrationconcentrated to a residue
12. customThe residue was recrystallized in hot heptane/ethyl acetate (1.8:1, 840 mL total volume) with initial
13. filtrationhot filtration (˜1 g of oily residues removed)
14. filtrationfinal filter cake
15. washwashing with heptane/ethyl acetate (3:1, 250 mL total volume)