Hydrochloric Acid → (3-amino-2-phenoxymethyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl)-(4-fluoro-phenyl)-methanone

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Reaction Steps

Tris(dibenzylideneacetone)dipalladium(0) (9.6 mg, 0.01 mmol) was added to a stirred suspension of (4-fluoro-phenyl)-(3-iodo-2-phenoxymethyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl)-methanone (50 mg, 0.1 mmol), sodium tert-butoxide (30 mg, 0.31 mmol) and rac-2,2′-bis(diphenylphosphino)-1,1′-binaphthyl (19.6 mg, 0.031 mmol) in toluene (2 mL) in a sealed tube and under N2. The mixture was stirred at room temperature for 5 minutes and then benzophenone imine (0.035 mL, 0.21 mmol) was added. The mixture was stirred at 100° C. for 2.5 hours. Then a 1M aqueous solution of HCl (3 mL) was added and the mixture was stirred at room temperature for 16 hours. The mixture was diluted with a saturated solution of Na2CO3 and water and extracted with DCM. The organic layer was separated, dried (MgSO4), filtered and the solvents evaporated in vacuo. The crude product was purified by flash column chromatography (silica; MeOH in DCM 0/100 to 6/94). The desired fractions were collected and the solvents evaporated in vacuo. The desired product was triturated with diethyl ether to yield (3-amino-2-phenoxymethyl-6,7-dihydro-4H-pyrazolo[1,5-a]pyrazin-5-yl)-(4-fluoro-phenyl)-methanone (18 mg, 47% yield) as a white solid. C20H19FN4O21H NMR (500 MHz, CDCl3) δ ppm 1.53 (s, 1H), 2.86 (br. s., 1H), 3.99 (br. s., 2H), 4.18 (br. s., 2H), 4.70 (br. s., 2H), 5.08 (s, 2H), 6.97 (t, J=7.4 Hz, 1H), 7.02 (d, J=8.1 Hz, 2H), 7.15 (t, J=8.7 Hz, 2H), 7.30 (dd, J=8.4, 7.5 Hz, 2H), 7.49 (dd, J=8.5, 5.3 Hz, 2H).

Provenance & Evidence