反应详情

A mixture of 5-(2-(methoxymethyl)-4-methyl-1H-imidazol-5-yl)-2,4-dimethylbenzoic acid (compound 2.3, 140 mg, 0.51 mmol), EDC.HCl (150 mg, 0.78 mmol), 4-dimethylaminopyridine (190 mg, 1.56 mmol), and HOBT (80 mg, 0.59 mmol) in N,N-dimethylformamide (6 mL). The mixture was stirred at room temperature, then after 15 min, 4-(piperidin-4-yl)benzonitrile hydrochloride (compound 1.2, 100 mg, 0.45 mmol) was added. The resulting solution was stirred for 15 h at room temperature, then quenched with 20 mL of H2O. The aqueous was extracted with ethyl acetate (40 mL) and the combined organics was washed with brine (2×30 mL), dried (Na2SO4), filtered, and concentrated under reduced pressure. The residue was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU)): Column, SunFire Prep C18 OBD Column, 5 um, 19*150 mm; mobile phase, water with 0.05% TFA and CH3CN (23% CH3CN up to 38% in 7 min, up to 100% in 2 min, down to 23% in 1 min); Detector, Waters 2489, 254 &220 nm. The fractions containing pure compound were combined and lyophilized to yield the title compound as a white solid (70.4 mg, 35%).

1. stirringThe resulting solution was stirred for 15 h at room temperature
2. customquenched with 20 mL of H2O
3. extractionThe aqueous was extracted with ethyl acetate (40 mL)
4. washthe combined organics was washed with brine (2×30 mL)
5. dry with materialdried (Na2SO4)
6. filtrationfiltered
7. concentrationconcentrated under reduced pressure
8. customThe residue was purified by Prep-HPLC with the following conditions (1#-Pre-HPLC-001(SHIMADZU))
9. waitmobile phase, water with 0.05% TFA and CH3CN (23% CH3CN up to 38% in 7 min
10. waitup to 100% in 2 min
11. waitdown to 23% in 1 min)
12. additionThe fractions containing pure compound