Hydrochloric Acid → HCID 16066664, compound

Participants

Reaction Steps

The 5,7-dichloro-1-(2-ethoxyethyl)-3-ethyl-1H-pyrazolo[4,3-d]pyrimidine prepared in step 4 (1 mmol), 2-amino-4-picoline (2 mmol), N,N-diisopropylethylamine (3 mmol), and N-methylpyrrolidone (1 mL) were added to each of two reaction vessels. Each vessel was irradiated in a CEM Discover microwave for 15 minutes at 150° C. Isonipecotic acid (3 mmol) was added to each reaction vessel and the resulting mixture irradiated for 15 minutes at 180° C. The contents of the two reaction vessels were combined. Water and ethyl acetate was added to the mixture and the mixture was shaken. Hydrochloric acid (1M) was added to the mixture and the mixture was shaken again. The layers were separated. The organic layer was washed with water, hydrochloric acid (1M) was added, and the layers were separated. The organic layer was dried over magnesium sulfate, filtered, and evaporated. The pH of the aqueous layer was raised to about six by adding saturated sodium carbonate and the aqueous layer was then extracted with ethyl acetate. The organic layer was dried over magnesium sulfate, filtered, added to the above organic residue and evaporated. The solution was purified by RP-HPLC on a Varian Dynamax C-18 column (250×41.4 mm) with a gradient of 10-95% acetonitrile/water (hydrochloric acid) over 15 minutes in two batches. Fractions were combined and evaporated to afford 0.26 g of the title compound. 1H NMR (400 MHz, DMSO-d6): 1.10 (t, 3 H), 1.30 (t, 3 H), 1.49-1.60 (m, 2 H), 1.84-1.95 (m, 2 H), 2.32-2.36 (m, 3 H), 2.52-2.57 (m, 1 H), 2.78 (q, 2 H), 2.99-3.08 (m, 2 H), 3.52 (q, 2 H), 3.78 (t, 2 H), 4.45-4.53 (m, 2 H), 4.56-4.64 (m, 2 H), 6.91 (d, 1 H), 8.05 (s, 1 H), 8.18 (d, 1 H), 9.63 (s, 1 H), 12.18 (s, 1 H). LCMS m/z 454.

Provenance & Evidence