反应详情

To a stirred solution of crude N-(4-fluorobenzyl)-3-hydroxy-9-(methylamino)-4-oxo-6,7,8,9-tetrahydro-4H-pyrido[1,2-a]pyrimidine-2-carboxamide (synthesized as described in Example 3, Step 3) in dichloromethane were added 6 eq. of triethylamine and 6 eq. of methyl chlorooxoacetate. The mixture was stirred at room temperature for 2 h, the solvent was removed under reduced pressure and the residue was dissolved in a solution of dimethylamine (2 M) in tetrahydrofuran. The mixture was stirred at 57° C. overnight. After cooling to room temperature, the solvent was removed under reduced pressure and the product was isolated by preparative RP-HPLC, using water (0.1% TFA) and acetonitrile (0.1% TFA) as eluents (column: C18). The pooled product fractions were lyophilized to afford the title compound as a fluffy, slightly pink material. The product was a mixture of rotamers by NMR.

1. customthe solvent was removed under reduced pressure
2. dissolutionthe residue was dissolved in a solution of dimethylamine (2 M) in tetrahydrofuran
3. stirringThe mixture was stirred at 57° C. overnight
4. temperatureAfter cooling to room temperature
5. customthe solvent was removed under reduced pressure
6. customthe product was isolated by preparative RP-HPLC