Diisopropylethylamine → N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-[4-(1,3-oxazol-2-ylmethyl)piperazin-1-yl]-2-oxoethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide

Participants

Reaction Steps

To a solution of 2-[3-[5-chloro-2-(difluoromethoxy)phenyl]-4-[pyrazolo[1,5-a]-pyrimidine-3-amido]-1H-pyrazol-1-yl]acetic acid (100 mg, 0.22 mmol) in DMF (10 mL) was added 1-(1,3-oxazol-2-ylmethyl)piperazine hydrochloride (132 mg, 0.65 mmol), HATU (123 mg, 0.32 mmol), DIEA (139 mg, 1.08 mmol). The resulting solution was stirred at room temperature overnight. Water (50 mL) and DCM (30 mL) was added. Phases were separated. The aqueous phase was extracted with DCM (×2) and the organic layers combined. The organic layers were washed with brine, dried over Na2SO4 and concentrated under vacuum. The crude product (150 mg) was purified by Prep-HPLC with the following conditions (2#-AnalyseHPLC-SHIMADZU(HPLC-10)): Column, XBridge BEH130 Prep C18 OBD Column, 19� 100 mm 5 um 13 nm; mobile phase, Water with 10 mM NH4HCO3 and ACN (28% ACN up to 38% in 6 min); Detector, UV 254/220 nm. This resulted in 68.2 mg (52%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-[4-(1,3-oxazol-2-ylmethyl)piperazin-1-yl]-2-oxoethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as an off-white solid. LCMS (Method 25) [M+H]+=612.1, RT=1.70 min. 1H NMR (300 MHz, DMSO-d6) δ: (ppm) 9.75 (s, 1H), 9.34 (dd, 1H, J=1.7, 7.1 Hz), 8.69-8.67 (m, 2H), 8.30 (s, 1H), 8.09 (d, 1H, J=0.6 Hz), 7.62 (dd, 1H, J=2.7, 8.7 Hz), 7.55 (d, 1H, J=2.7 Hz), 7.45 (d, 1H, J=9.0 Hz), 7.28 (dd, 1H, J=4.2, 7.2 Hz), 7.18 (d, 1H, J=0.6 Hz), 7.01 (t, 1H, J=73.2 Hz), 5.23 (s, 2H), 3.76 (s, 2H), 3.54-3.48 (m, 4H), 2.45-2.42 (m, 4H).

Provenance & Evidence