Reaction Steps
To a solution of 4,6-dimethyl-pyrimidine-5-carboxylic acid (3-{4-[(4-amino-phenyl)-(3-cyano-benzyl)-amino]-piperidin-1-yl}-butyl)-amide (see EXAMPLE 154) (54 mg, 0.10 mmol) in toluene (1 mL) was added phosgene (20% in toluene, 82 μL, 0.15 mmol) and the resultant slurry was stirred at room temperature for 3.5 hours. The mixture was concentrated under reduced pressure and the residue was dissolved in DMF (1 mL). To the solution were added ammonium chloride (28 mg, 0.53 mmol) and DIPEA (110 μL, 0.64 mmol) and the mixture was stirred at room temperature for 25 hours. Standard work-up and purification afforded COMPOUND 159 as a white solid (23 mg, 39%). 1H NMR (CDCl3) δ0.90-1.10 (m, 5H), 1.54 (d, 1H, J=13.5 Hz), 1.74-1.83 (m, 3H), 2.17 (t, 1H, J=11.1 Hz), 2.50 (s, 6H), 2.56 (t, 1H, J=11.1 Hz), 2.73-2.84 (m, 3H), 3.31 (m, 1H), 3.56 (m, 1H), 3.82-3.89 (m, 1H), 3.89 (s, 2H), 4.72 (s, 2H), 6.51 (d, 2H, J=8.1 Hz), 6.58 (s, 1H), 7.05 (d, 2H, J=8.1 Hz), 7.41-7.56 (m, 4H), 8.62 (br s, 1H), 8.85 (s, 1H). 13C NMR (CDCl3) δ 13.44, 21.94, 29.21, 30.42, 30.73, 40.05, 43.58, 48.57, 51.99, 53.45, 56.55, 60.24, 112.55, 117.73, 118.98, 125.26, 128.41, 129.36, 129.93, 130.67, 130.88, 131.02, 141.60, 145.94, 157.52, 157.75, 163.11, 166.29. ES-MS m/z 555 (M+H). Anal. Calcd. for C31H38N8O2.0.8CH2Cl2: C, 61.34; H, 6.41; N, 18.00. Found. C, 61.52; H, 6.49; N, 17.93.
