Acetonitrile → 5-Ethynylpyrimidin-2-amine

A flask was charged with 5-iodopyrimidin-2-amine (25.0 g, 110 mmol), acetonitrile (900 ml, 110 mmol), trimethylsilylacetylene (35 ml, 241 mmol), triethylamine (93 ml, 658 mmol), Pd(PPh3)4Cl2 (3.9 g, 5.5 mmol) and finally copper(I) iodide (1.1 g, 5.5 mmol). The flask was put under vacuum then filled with argon and stirred at RT overnight using a mechanical stirrer. The solvent was removed under vacuum, the residue taken up in methanol (600 ml) and potassium carbonate (152 g, 1097 mmol) was added. The mixture was stirred at RT using mechanical stirring for 2 hrs. Activated carbon (˜50 mL) was added to the reaction and stirring continued for 15 min. The reaction mixture was then filtered through a plug of celite and the filtrate was concentrated to a volume of ˜400 mL and the precipitate was filtered. The filtrate was concentrated down to a thick paste which was slurried in ˜150 mL of 10% MeOH/H2O for 20 min at RT. The solids were then filtered off to afford 5-ethynylpyrimidin-2-amine.

1. additionthen filled with argon
2. customThe solvent was removed under vacuum
3. stirringThe mixture was stirred at RT
4. stirringusing mechanical stirring for 2 hrs
5. additionActivated carbon (˜50 mL) was added to the reaction
6. stirringstirring
7. waitcontinued for 15 min
8. filtrationThe reaction mixture was then filtered through a plug of celite
9. concentrationthe filtrate was concentrated to a volume of ˜400 mL
10. filtrationthe precipitate was filtered
11. concentrationThe filtrate was concentrated down to a thick paste which
12. waitwas slurried in ˜150 mL of 10% MeOH/H2O for 20 min at RT
13. filtrationThe solids were then filtered off

ORD record

ord-79debf2e8a7e4b6cbe86f6faf9e1868c

Source dataset

uspto-grants-2011_02

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US07893061B2