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0 °C

A solution of 4-chloro-2-methylthio-5-pyrimidinecarboxylate (900 mg, 3.87 mmol) (Aldrich) and triethylamine (1.1 mL, 870 mg, 7.74 mmol) (Aldrich) in dioxane (50 mL) was treated with (±)-trans-3-(tert-butyl-dimethyl-silanyloxy)-cyclopentylamine (840 mg, 3.87 mmol) (from Example 9c supra). The mixture was stirred at reflux for 1 hour, then cooled and partitioned between brine and ethyl acetate. The organic layer was collected, dried over sodium sulfate, filtered and concentrated to a residue that was purified by silica gel column chromatography using a 0–20% ethyl acetate in hexanes gradient. The product isolated from this purification was then dissolved in anhydrous tetrahydrofuran (80 mL) and the resulting solution was cooled to 0° C. Followed addition in-portions of lithium aluminum hydride (440 mg, 11.61 mmol) (Aldrich) and the resulting mixture was allowed to warm to room temperature. After overnight stirring the reaction mixture was poured slowly into a vigorously stirred mixture of ethyl acetate and saturated aqueous potassium sodium tartrate solution. The organic layer was collected, dried over sodium sulfate, filtered and concentrated to an off white solid. This intermediate was then dissolved in dichloromethane (80 mL) and the resulting solution was treated with manganese dioxide (3.36 g, 38.70 mmol) (Aldrich). After overnight stirring the solids were filtered off, washed with tetrahydrofuran (approximately 30 mL) and the combined organic layer was concentrated to a residue that upon a silica gel column purification with 0–50% diethyl ether in hexanes gradient gave (±)-4-[trans-3-(tert-butyl-dimethyl-silanyloxy)-cyclopentylamino]-2-methylsulfanyl-pyrimidine-5-carbaldehyde as a viscous colorless oil. (Yield 888 mg, 62%).

1. temperatureat reflux for 1 hour
2. temperaturecooled
3. custompartitioned between brine and ethyl acetate
4. customThe organic layer was collected
5. dry with materialdried over sodium sulfate
6. filtrationfiltered
7. concentrationconcentrated to a residue that
8. customwas purified by silica gel column chromatography
9. customThe product isolated from this purification
10. temperatureto warm to room temperature
11. stirringAfter overnight stirring the reaction mixture
12. customThe organic layer was collected
13. dry with materialdried over sodium sulfate
14. filtrationfiltered
15. concentrationconcentrated to an off white solid
16. dissolutionThis intermediate was then dissolved in dichloromethane (80 mL)
17. stirringAfter overnight stirring the solids
18. filtrationwere filtered off
19. washwashed with tetrahydrofuran (approximately 30 mL)
20. concentrationthe combined organic layer was concentrated to a residue that upon a silica gel column purification with 0–50% diethyl ether in hexanes gradient