Nitrogen → HCID 178495865, compound

Participants

Reaction Conditions

Reaction Steps

To a mixture of (3-bromo-pyrazolo[1,5-a]pyrimidin-5-yl)-(2-methoxy-ethyl)-amine (307.7 mg, 1.1 mmol), (4-(1H-tetrazol-5-yl)phenyl)boronic acid [179942-55-3] (259.6 mg, 1.4 mmol), potassium phosphate tribasic monohydrate [27176-10-9] (522.4 mg, 2.3 mmol), and [1,1′-bis(diphenylphosphino)ferrocene]dichloro-palladium(II), complex with dichloromethane [95464-05-4] (106.3 mg, 0.1 mmol) contained in a 50 mL round bottomed flask was added a solution of 30% (v/v) water in 1,2-dimethoxyethane (12 mL) and a magnetic stir bar. The reaction pot was fitted to a reflux condenser, lowered into an ambient temperature oil bath, and the system taken through 10 evacuation/N2 blanket cycles while being rapidly stirred. The rapidly stirred, N2 blanketed, reaction was heated to an oil bath temperature of 85° C. for 4 h then cooled, diluted with methanol, and gravity filtered. The filtrate was preabsorbed on silica gel and flash chromatographed (silica gel eluted with 1% NH4OH in 10% (v/v) methanol/ethyl acetate). Desired chromatography fractions were combined, evaporated, redissolved in 2-propanol and gravity filtered into stirring heptane to precipitate purified product. (2-Methoxy-ethyl)-{3-[4-(1H-tetrazol-5-yl)-phenyl]-pyrazolo[1,5-a]pyrimidin-5-yl}-amine was isolated by filtration as 96.3 mg of solid material, mp. 264-265° C. (dec.). 1H NMR (400 MHz, DMSO-d6) δ ppm 3.63 (t, J=4.29 Hz, 5 H) 6.41 (d, J=7.58 Hz, 1 H) 7.88 (br. s., 1 H) 8.04 (m, J=8.59 Hz, 2 H) 8.31 (m, J=8.34 Hz, 2 H) 8.47 (s, 1 H) 8.53 (d, J=7.58 Hz, 1 H). 13C NMR (100 MHz, DMSO-d6) δ ppm 40.69, 58.48, 70.48, 100.86, 103.75, 119.86, 125.23, 127.61, 135.97, 137.08, 142.42, 145.63, 156.60, LRMS (ESI) m/z 337.2 [(M+H)]+, calc'd for C16H16N8O: 336.36.

Provenance & Evidence