Acetonitrile → 4-chloro-5-isopropyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine

Temperature

80 °C

A solution of 5-isopropyl-6,7-dihydro-5H-cyclopenta[d]pyrimidin-4-ol (4.29 g, 24.09 mmol) in acetonitrile (94.75 mL, 1814 mmol) was treated with POCl3 (6.62 mL, 72.28 mmol). The mixture was heated at 80° C. overnight. No reaction was observed by LC-MS or HPLC. An additional 3 equivalents of POCl3 were added, and the reaction was heated at 80° C. for 4 hours. The reaction was charged with an additional 10 equivalents of POCl3 and TEA (6.716 mL, 48.18 mmol) and heated at 80° C. overnight. The reaction was cooled to room temperature, and the solvent and POCl3 were removed under reduced pressure. The residue was taken up in DCM and was carefully added to stirring saturated NaHCO3. The mixture was stirred for 1 hour to confirm complete neutralization. The organics were combined and washed with brine, dried Na2SO4, filtered, and concentrated under reduced pressure. The crude material was purified by column chromatography (25% EtOAc/Hexane) to yield 4-chloro-5-isopropyl-6,7-dihydro-5H-cyclopenta[d]pyrimidine (1.23 g, 26%). LCMS (APCI+) m/z 196.9 [M+H]+; Rt=3.57 min.

1. temperaturethe reaction was heated at 80° C. for 4 hours
2. temperatureheated at 80° C. overnight
3. temperatureThe reaction was cooled to room temperature
4. customthe solvent and POCl3 were removed under reduced pressure
5. additionwas carefully added
6. stirringThe mixture was stirred for 1 hour
7. washwashed with brine, dried Na2SO4
8. filtrationfiltered
9. concentrationconcentrated under reduced pressure
10. customThe crude material was purified by column chromatography (25% EtOAc/Hexane)

ORD record

ord-7070a0ffde994fe5bb4e274b9811e97a

Source dataset

uspto-grants-2016_05

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US09346805B2