1,1'-Carbonyldiimidazole → HCID 86629517, compound

Participants

Reaction Conditions

Reaction Steps

To a solution of glycine t-butyl ester hydrochloride (74 mg, 0.44 mmol) in CH3CN (5 ml) was added CDI (71 mg, 0.44 mmol), followed by DIPEA (0.077 mL, 0.44 mmol), and the mixture was stirred at 60° C. for 2 h. A solution of 2,6-dichloro-4-methyl-N—((R)-3-{4-[(thiophen-3-ylmethyl)-amino]-piperidin-1-yl}-butyl)-nicotinamide (50 mg, 0.11 mmol) in CH3CN (5 ml) was then added to the previous mixture. After stirring at 60° C. overnight, the mixture was concentrated in vacuo and diluted with CH2Cl2 (15 ml) and saturated NaHCO3 (20 ml). The aqueous layer was extracted with CH2Cl2 (3×10 ml), then the combined organic extracts were dried over Na2SO4 and concentrated. The crude product was purified by flash chromatography (CH2Cl2, 5% MeOH, 1% NH4OH) to afford [3-(1-{(R)-3-[(2,6-dichloro-4-methyl-pyridine-3-carbonyl)-amino]-1-methyl-propyl}-piperidin-4-yl)-3-thiophen-3-ylmethyl-ureido]-acetic acid tert-butyl ester as a clear oil (95 mg). 1H NMR (CDCl3) δ 0.96-0.98 (d, 3H, J=6 Hz), 1.11-1.38 (m, 2H), 1.42 (s, 9H), 1.48-1.57 (m, 1H), 1.61-1.79 (m, 3H), 2.10-2.23 (m, 1H), 2.34 (s, 3H), 2.50-2.58 (m, 1H), 2.73-2.93 (m, 3H), 3.24-3.38 (m, 1H), 3.81-3.85 (d, 2H, J=12 Hz), 3.89 (s, 2H), 4.11-4.23 (m, 1H), 4.76-4.82 (m, 1H), 7.04-7.06 (d, 1H, J=6 Hz), 7.09 (s, 1H), 7.20 (s, 1H), 7.33-7.35 (d, 1H, J=6 Hz), 7.66 (br s, 1H), 8.90 (br s, 1H).

Provenance & Evidence