2-Amino-5-bromopyrimidine → Tert-butyl (2-aminopyrimidin-5-yl)acetate

Temperature

60 °C

A 1 L RB flask was charged with 2-amino-5-bromopyrimidine (8.75 g, 50.3 mmol). THF (262 ml) was added followed by tris(dibenzylideneacetone)dipalladium(0) (0.94 g, 1.027 mmol), X—PHOS (0.978 g, 2.05 mmol) and 2-(tert-butoxy)-2-oxoethylzinc chloride (262 mL, 131 mmol). It was heated at 60° C. (oil bath temperature) overnight. An additional tris(dibenzylideneacetone)dipalladium(0) (500 mg, 0.546 mmol) was added followed by X—PHOS (520 mg, 1.09 mmol). The reaction mixture was heated at reflux for 42 hours. The reaction mixture was then cooled to RT and quenched by addition of saturated NH4Cl solution and the layers separated. The aqueous phase was extracted with EtOAc(2×200 mL). The organic extracts were combined, washed with brine, dried (MgSO4), filtered and the solvent evaporated. The crude product was purified by flash chromatography on silica using a gradient from EtOAc: Hex. 3:2 to EtOAc to afford the title compound.

1. temperatureThe reaction mixture was heated
2. temperatureat reflux for 42 hours
3. temperatureThe reaction mixture was then cooled to RT
4. customquenched by addition of saturated NH4Cl solution
5. customthe layers separated
6. extractionThe aqueous phase was extracted with EtOAc(2×200 mL)
7. washwashed with brine
8. dry with materialdried (MgSO4)
9. filtrationfiltered
10. customthe solvent evaporated
11. customThe crude product was purified by flash chromatography on silica using a gradient from EtOAc

ORD record

ord-0e610e47ebe44fac8a33c9a45d57ff91

Source dataset

uspto-grants-2015_12

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09206199B2