反应详情

To a solution of ethyl 5-hydroxypyrazolo[1,5-a]pyrimidine-3-carboxylate (Preparation B, Step A, 372 mg, 1.8 mmol) in DMF (10 mL) was added (benzotriazol-1-yloxy)tris(dimethylamino)phosphonium hexafluorophosphate (874 mg, 1.98 mmol). The mixture was stirred at ambient temperature for 10 minutes then treated with DIEA (1.57 mL, 8.99 mmol) and (R)-5-fluoro-2-methyl-3-(pyrrolidin-2-yl)pyridine dihydrochloride (455 mg, 1.80 mmol). After stirring at ambient temperature for 4 hours the mixture was partitioned between 10% citric acid (50 mL) and EtOAc (50 mL). The layers were separated and the aqueous layer was extracted with EtOAc (2×30 mL). The combined organic phases were washed successively with water (30 mL), saturated NaHCO3 (30 mL), water (30 mL) and brine (2×30 mL), then dried over Na2SO4, filtered and concentrated. The residue was purified by silica gel column chromatography eluting with 1% MeOH/DCM to afford the product as white foam (480 mg, 72% yield). MS (apci) m/z=370.0 (M+H).

1. stirringAfter stirring at ambient temperature for 4 hours the mixture
2. customwas partitioned between 10% citric acid (50 mL) and EtOAc (50 mL)
3. customThe layers were separated
4. extractionthe aqueous layer was extracted with EtOAc (2×30 mL)
5. washThe combined organic phases were washed successively with water (30 mL), saturated NaHCO3 (30 mL), water (30 mL) and brine (2×30 mL)
6. dry with materialdried over Na2SO4
7. filtrationfiltered
8. concentrationconcentrated
9. customThe residue was purified by silica gel column chromatography
10. washeluting with 1% MeOH/DCM