Phosphorus oxychloride → 6-Bromo-4-chloropyrido[2,3-d]pyrimidine

6-Bromopyrido[2,3-d]pyrimidin-4(3H)-one (3.0 g) and POCl3 (15 mL) were heated at 130° C. under nitrogen for 3 h. The homogeneous dark solution was concentrated under reduced pressure and diluted with EtOAc (150 mL). The heterogeneous brown slurry was poured onto mixture of ice/aq. NaHCO3 and allowed the mixture warm to room temperature. The heterogeneous brown mixture was further diluted with EtOAc (75 mL) and separated the organic layer. The organic layer was partitioned with aq. NaCl, separated, stirred with MgSO4 and filtered through a pad of Celite® and silica gel. The pale yellow filtrate was concentrated and the crude solid was stirred in 50% EA/hexanes. 6-Bromo-4-chloropyrido[2,3-d]pyrimidine was obtained as a pale yellow crystalline solid (1.8 g, purity: 95%) upon filtration.

1. concentrationThe homogeneous dark solution was concentrated under reduced pressure
2. additiondiluted with EtOAc (150 mL)
3. additionThe heterogeneous brown slurry was poured onto mixture of ice/aq
4. additionThe heterogeneous brown mixture was further diluted with EtOAc (75 mL)
5. customseparated the organic layer
6. customThe organic layer was partitioned with aq. NaCl
7. customseparated
8. filtrationfiltered through a pad of Celite® and silica gel
9. concentrationThe pale yellow filtrate was concentrated
10. stirringthe crude solid was stirred in 50% EA/hexanes

ORD record

ord-8f38e3a1d88f4e6e99f6d1c36bd0fcfa

Source dataset

uspto-grants-2015_09

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09145433B2