Trifluoroacetic acid → HCID 178448286, compound

Participants

Reaction Steps

8-Bromo-2-{[(1S)-1-methylbutyl]oxy}-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-6-amine (1.26 kg, corrected for residual solvent) was dissolved in anhydrous methyl tetrahydrofuran (MeTHF) (11.4 L) and 25% sodium methoxide in methanol (2.65 L, 3.5 eq) was added. The resultant reaction mixture was heated to 65+/−5° C. for 3 hrs. The complete reaction was cooled to room temperature and washed with 20% w/v aqueous ammonium chloride solution (2×6.3 L) and brine (6.3 L). The organic phase was dried with MgSO4 (1.8 kg) and filtered, washing through with MeTHF (6.3 L). The combined organic phases were evaporated to 6.3 L by vacuum distillation. MeOH (2.5 L) and TFA (1.26 L, 5 eq) were added and the mixture heated to 60° C. for 1.5 hours. Cyclopentyl methyl ether (CPME) (6.3 L) was added and the mixture reduced to 6.3 L by vacuum distillation. CPME (6.3 L) was again added and the reaction further concentrated to 6.3 L, when solids precipitated. The slurry was cooled to 10° C. then aged for 30 min. The product was filtered and washed with TBME (2×3.8 L) and dried in vacuo at 40° C. to afford a white solid (886 g, 74% theoretical yield).

Provenance & Evidence