Toluene → 4-Chloro-6-cyclopropylpyrimidine

Temperature

100 °C

To a stirred solution of 4,6-dichloropyrimidine (200 mg, 1.342 mmol) in toluene (5.00 mL) in a 2 mL microwave vial was added potassium cyclopropyl(trifluoro)borate (219 mg, 1.477 mmol) (Frontier Scientific Inc.), di(1-adamantyl)-n-butylphosphine (14.44 mg, 0.040 mmol), palladium(II) acetate (6.03 mg, 0.027 mmol) and cesium carbonate (1312 mg, 4.03 mmol) and stirred under argon at 100° C. for 24 hrs in a microwave reactor. The reaction mixture was washed with water (50 mL) and extracted with ethyl acetate (3×20 mL). The organic layers were collected, dried (MgSO4) and evaporated to dryness in vacuo to afford a crude residue. Crude residues were then purified on Biotage Isolera Four (25 g pre-packed cartridge) eluting with 0-15% ethyl acetate-isohexane. The appropriate fractions were combined and evaporated in vacuo to give the title compound as a pale yellow solid (80 mg).

1. washThe reaction mixture was washed with water (50 mL)
2. extractionextracted with ethyl acetate (3×20 mL)
3. customThe organic layers were collected
4. dry with materialdried (MgSO4)
5. customevaporated to dryness in vacuo
6. customto afford a crude residue
7. customCrude residues were then purified on Biotage Isolera Four (25 g pre-packed cartridge)
8. washeluting with 0-15% ethyl acetate-isohexane
9. customevaporated in vacuo

ORD record

ord-8f4e569c559f4e788572948b6f3a6ab9

Source dataset

uspto-grants-2014_08

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08796283B2