Nitrogen → 7-(1-Ethyl-propyl)-3-(2,4-dichloro-thiazol-5-yl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine

Temperature

120 °C

Charge 7-(1-ethyl-propyl)-3-iodo-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine (1.03 g, 3.00 mmoles), K3PO4 (1.95 g, 9.00 mmoles), 2,4-dichlorothiazole (0.58 g, 3.75 mmoles), 1,10 phenanthroline (0.05 g, 0.30 mmoles) and anhydrous DMAC (5 mL) to a round bottom flask equipped with a magnetic stir bar, thermal couple and N2 inlet. Degas the yellow heterogeneous reaction mixture with N2 (gas) for 30 min. and then add CuI (0.06 g, 0.30 mmoles) in one portion followed by additional 30 min. degassing with N2 (gas). Stir the reaction mixture at 120° C. for about 6 hr. Cool the reaction mixture to room temperature overnight, add toluene (10 mL) and stir for 1 hr. Purify the mixture through silica gel eluting with toluene (10 ml). Extract with 1 M HCl (10 mL), water (10 mL), brine (10 mL) and concentrate under reduced pressure to give a yellow solid. Recrystallize the solid from methanol (5 ml) to yield the title compound as a yellow crystalline solid. (0.78 g, 70% yield, >99% pure by LC) MS (ES)=369 (M+1). 1H NMR (CDCl3)=6.5 (1H, s); 3.6 (1H, m); 2.6 (3H, s); 2.5 (3H, s); 1.9 (4H, m); 0.9 (6H, t).

1. customequipped with a magnetic stir bar
2. customDegas the yellow heterogeneous reaction mixture with N2 (gas) for 30 min.
3. customdegassing with N2 (gas)
4. temperatureCool the reaction mixture to room temperature overnight
5. additionadd toluene (10 mL)
6. stirringstir for 1 hr
7. customPurify the mixture through silica gel eluting with toluene (10 ml)
8. extractionExtract with 1 M HCl (10 mL), water (10 mL), brine (10 mL)
9. concentrationconcentrate under reduced pressure
10. customto give a yellow solid
11. customRecrystallize the solid from methanol (5 ml)

ORD record

ord-e81da3655835453dae1e8e6d9352def3

Source dataset

uspto-grants-2013_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08563718B2