Nitrogen → 1,1-Dimethylethyl (1S,4S)-5-[4-(5-fluoro-2-pyrimidinyl)phenyl]-2,5-diazabicyclo[2.2.1]heptane-2-carboxylate

Participants

Reaction Conditions

Reaction Steps

A mixed DMF/H2O (5 mL/5 mL) solution of (S,S)-5-[4-(4,4,5,5-Tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-2,5-diaza-bicyclo[2.2.1]heptane-2-carboxylic acid tert-butyl ester (800 mg, 2 mmol), 2-chloro-5-fluoro-pyrimidine (340 mg, 2.6 mmol), K2CO3 (552 mg, 4 mmol) and Cl2Pd(dppf)CH2Cl2 (160 mg) was evacuated and recharged with N2 several times. The reaction was heated at 70° C. over 18 hrs. After cooling down to rt, 40 mL ethyl acetate and 10 mL water was added. The mixture was filtered through a pad of Celite and washed with additional ethyl acetate. The separated organic layer was dried (MgSO4) and concentrated. The crude was purified on silica gel column eluting with 50% ethyl acetate/hexanes to yield the title compound (420 mg) as a light yellow solid.

Provenance & Evidence