Sodium cyanoborohydride → N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-[(1,3-oxazol-2-ylmethyl)amino]ethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide

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To a solution of N-[1-(2-aminoethyl)-3-[5-chloro-2-(difluoromethoxy)phenyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide (100 mg, 0.22 mmol) in MeOH (15 mL) was added 1,3-oxazole-2-carbaldehyde (21.7 mg, 0.22 mmol), followed by NaBH3CN (16 mg, 0.25 mmol). The resulting solution was stirred at room temperature for 12 h. The resulting mixture was concentrated under vacuum. The residue was passed through a short pad of silica gel eluting with 5% MeOH in DCM. The crude product 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 NH4CO3 and ACN (20% ACN up to 50% in 6 min); Detector, UV 254/220 nm. 52.7 mg product was obtained. This resulted in 52.7 mg (45%) of N-[3-[5-chloro-2-(difluoromethoxy)phenyl]-1-[2-[(1,3-oxazol-2-ylmethyl)amino]ethyl]-1H-pyrazol-4-yl]pyrazolo[1,5-a]pyrimidine-3-carboxamide as a light yellow solid. LCMS (Method 20) [M+H]+=529.2, RT=2.42 min. 1H NMR (300 MHz, CD3OD-d4) δ: (ppm) 9.08 (dd, 1H, J=1.7, 7.1 Hz), 8.66-8.63 (m, 2H), 8.34 (s, 1H), 7.87 (d, 1H, J=0.6 Hz), 7.67 (d, 1H, J=2.7 Hz), 7.53 (dd, 1H, J=2.4, 8.7 Hz), 7.38 (d, 1H, J=8.7 Hz), 7.19 (dd, 1H, J=4.2, 7.2 Hz), 7.13 (d, 1H, J=0.6 Hz), 6.55 (t, 1H, J=73.5 Hz), 4.33 (t, 2H, J=6.0 Hz), 3.95 (s, 2H), 3.14 (t, 2H, J=6.0 Hz).

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