反应详情

A solution of 6-methylpicolinic acid (9.4 mg, 0.07 mmol) in methylene chloride was treated with 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (84 mg) and DMAP (2 mg) at 23° C. After stirring for 10 min, N-[1-(cis-3-amino-cyclobutyl)-1H-imidazol-4-yl]-2-naphthalen-1-yl-acetamide (Example 6, 20 mg, 0.06 mmol), was added. The resulting mixture was then stirred for 3 h. Water was added, the solution was made neutral with aqueous NaOH and was extracted with ethyl acetate. The organic layer was dried (MgSO4), filtered, and concentrated in vacuo. Purification by silica gel chromatography (20:1 CHCl3—MeOH) gave 26 mg (95% yield) of 6-methyl-pyridine-2-carboxylic acid {3-[4-(2-naphthalen-1-yl-acetylamino)-imidazol-1-yl]-cyclobutyl}-amide; 1H NMR (400 MHz, CDCl3) δ9.15 (s, 1H), 8.28 (d, J=8.3 Hz, 1H), 8.01 (d, J=7.5 Hz, 1H), 7.96 (d, J=7.5 Hz, 1H), 7.97 (d, J=7.5 Hz, 1H), 7.81 (dd, J=2.4, 6.6 Hz, 1H), 7.72 (m, 1H), 7.5 (m, 5H), 7.2 (m, 1H), 7.16 (s, 1H), 4.45 (m, 1H), 4.25 (m, 1H), 4.18 (s, 2H), 2.98 (m, 2H), 2.60 (s, 3H), 2.40 (m, 2H); MS (AP/Cl): 440.3 (M+H)+.

1. stirringThe resulting mixture was then stirred for 3 h
2. extractionwas extracted with ethyl acetate
3. dry with materialThe organic layer was dried (MgSO4)
4. filtrationfiltered
5. concentrationconcentrated in vacuo
6. customPurification by silica gel chromatography (20:1 CHCl3—MeOH)