Ethyl Acetate → HCID 118081947, compound

Participants

Reaction Conditions

Reaction Steps

A mixture of 2-chloro-9-isopropyl-N-(4-(4-methylpiperazin-1-yl)phenyl)-9H-purin -6-amine (2.32 g, 6 mmol), (S)-pyrrolidin-3-yl-carbamic acid tert-butyl ester (1.45 g, 7.8 mmol, 1.3 mol eq), and Cs2CO3 (7.82 g, 24 mmol, 4 mol eq) in tert-pentyl alcohol (60 mL, 0.1 M) was degassed with nitrogen. Chloro(di-2-norbornylphosphino)(2-dimethylaminomethylferrocen-1-yl)palladium(II) (CAS #614753-51-4, 375 mg, 0.6 mmol, 0.1 mol eq) was added, and the mixture degassed for 1 additional min. The vial was capped, stirred and heated at 100° C. (block temperature) for 20 hr. The reaction was cooled, diluted with water (25 mL) and ethyl acetate (150 mL) and the organic layer was separated. The aqueous layer was extracted with more ethyl acetate (50 mL) and the combined organics were dried over Na2SO4 and evaporated to give a residue that was purified via silica flash chromatography with a gradient of 50% heptane-50% ethyl acetate to 100% ethyl acetate and then to 10% ammonia (7 N in methanol)-90% ethyl acetate to give the title product as a light yellow solid (3.20 g, 99% yield). 1H NMR (400 MHz, DMSO d6) δ ppm 9.14 (s, 1 H) 7.90 (s, 1 H) 7.85 (d, J=9.05 Hz, 2 H) 7.14 (d, J=5.01 Hz, 1 H) 6.87 (d, J=9.17 Hz, 2 H) 4.61 (quin, J=6.72 Hz, 1 H) 4.05-4.27 (m, 2 H) 3.60-3.80 (m, 2 H) 3.50 (dt, J=10.55, 7.08 Hz, 1 H) 3.35 (dd, J=10.82, 4.83 Hz, 1 H) 3.02-3.11 (m, 4 H) 2.40-2.48 (m, 4 H) 2.22 (s, 3 H) 1.79-1.92 (m, 1 H) 1.50 (d, J=6.85 Hz, 6 H) 1.40 (s, 9 H). m/z (APCI+) for C28H41N9O2 536.4 (M+H)+.

Provenance & Evidence