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0 °C

Dissolve 3-(3-methyl-thiophene-2-yl)-7-(1-ethyl-propyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine (0.419 g, 1.33 mmol) in dichloromethane (2.5 mL), stir under an inert atmosphere, chill in an ice bath to 0° C. and add trifluoroacetic acid (5 mL). Add concentrated (70%) nitric acid (0.132 g, 1.47 mmol) to the reaction dropwise. The solution changes color from yellow to dark green. Stir 1 h under an inert atmosphere while in an ice bath and confirm the reaction is complete using TLC. Dilute the reaction with dichloromethane (80 mL) and quench with saturated sodium bicarbonate. Separate and extract the aqueous basic phase with dichloromethane (50 mL). Combine the organic phases, dry over anhydrous magnesium sulfate, filter, and concentrate under reduced pressure. Purify the resulting residue using flash chromatography, eluting with 100% hexane/0% (30% ethyl acetate/hexane) to 0% hexane/100% (30% ethyl acetate/hexane) in a step gradient of 10% increments to give a yellow solid (0.363 g, 76%). 1H NMR (400 MHz, CDCl3): δ 7.81 (s, 1H), 6.51 (s, 1H), 3.62-3.58 (m, 1H), 2.56 (s, 3H), 2.48 (s, 3H), 2.18 (s, 3H), 1.88-1.70 (m, 4H), 0.88 (t, J=7.5 Hz, 6H).

1. additionAdd
2. customto the reaction dropwise
3. stirringStir 1 h under an inert atmosphere while in an ice bath
4. additionDilute
5. customquench with saturated sodium bicarbonate
6. customSeparate
7. extractionextract the aqueous basic phase with dichloromethane (50 mL)
8. dry with materialCombine the organic phases, dry over anhydrous magnesium sulfate
9. filtrationfilter
10. concentrationconcentrate under reduced pressure
11. customPurify the resulting residue
12. washeluting with 100% hexane/0% (30% ethyl acetate/hexane) to 0% hexane/100% (30% ethyl acetate/hexane) in a step gradient of 10% increments