反应详情

Combine a mixture of 4-chloro-7-(2,4-dimethoxybenzyl)-5H-pyrrolo[2,3-d]pyrimidin-6(7H)-one (1.10 equiv; 868.3 mmol; 277.63 g) in methanol (62.44 mol; 2.53 L) at RT, a solution of 2-(4-(4-fluoro-3-(trifluoromethyl)phenyl)-2-(piperidin-4-yl)-1H-imidazol-1-yl)-N,N-dimethylethanamine dihydrochloride (1.00 equiv; 789.35 mmol; 361.0 g) and TEA (9077 mmol; 1265 mL) in methanol (62.44 mol; 2.53 L) and stir the mixture overnight at 55-60° C. Partition the reaction mixture between water (10 L) and EA (10 L). Extract the organic layer with 2 N HCl (5 L). Separate and extract the aqueous layer with EA (5 L). An oil separates in the aqueous layer. Decant the aqueous liquid and hold the oil for recovery of product. Stir the decanted aqueous layer with EA (5 L) and adjust the pH of the mixture to 10-11 with 2 N NaOH. Separate the organic layer, wash with brine, and dry over Na2SO4. Filter and evaporate the solvent to give the title compound (473.3 mmol; 316.0 g; 60%).

1. customPartition the reaction mixture between water (10 L) and EA (10 L)
2. extractionExtract the organic layer with 2 N HCl (5 L)
3. customSeparate
4. extractionextract the aqueous layer with EA (5 L)
5. customDecant the aqueous liquid
6. customSeparate the organic layer
7. washwash with brine
8. dry with materialdry over Na2SO4
9. filtrationFilter
10. customevaporate the solvent