Phosphorus oxychloride → HCID 86662696, compound

Temperature

115 °C

To 2-[difluoro-(5-fluoro-pyridin-2-yl)-methyl]-8-methyl-3H-quinazolin-4-one (0.23 g, 0.76 mmol) were added DIEA (0.27 mL, 1.5 mmol) and POCl3 (5 mL, 55 mmol) and the mixture was heated at 115° C. for 6 h. The mixture was allowed to cool to rt and the mixture was concentrated under reduced pressure. The residue was treated with toluene and concentrated to dryness twice. The residue was partitioned between EtOAc (20 mL) and cold saturated aq NaHCO3 (10 mL). The separated EtOAc layer was diluted with of EtOAc (60 mL) and washed with saturated aq NaHCO3 (10 mL) and brine (10 mL×2), dried over MgSO4, filtered and concentrated under reduced pressure to afford 4-chloro-2-[difluoro-(5-fluoro-pyridin-2-yl)-methyl]-8-methyl-quinazoline as a brown viscous oil (242 mg, 99%).

1. temperatureto cool to rt
2. concentrationthe mixture was concentrated under reduced pressure
3. additionThe residue was treated with toluene
4. concentrationconcentrated to dryness twice
5. customThe residue was partitioned between EtOAc (20 mL) and cold saturated aq NaHCO3 (10 mL)
6. additionThe separated EtOAc layer was diluted with of EtOAc (60 mL)
7. washwashed with saturated aq NaHCO3 (10 mL) and brine (10 mL×2)
8. dry with materialdried over MgSO4
9. filtrationfiltered
10. concentrationconcentrated under reduced pressure

ORD record

ord-3d92083730354ec0a496a11126cfbe51

Source dataset

uspto-grants-2014_01

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08633207B2