81% |
With triethylamine; HATU; In acetonitrile; at 20℃; for 16h; |
Example 79 2-(1H-benzo[d]imidazole-2-yl)-N-(5-isopropyl-2-methylphenyl)acetamide 2-(1H-benzo[d]imidazole-2-yl)acetic acid (100 mg, 0.57 mmol), O-(7-azabenzotriazol-1-yl)-M,M,N',N'-tetramethyluronium hexafluorophosphate (HATU, 433 mg, 1.14 mmol) are dissolved into acetonitrile (7 mL). Triethylamine (TEA, 160 muL, 1.14 mmol) is added thereto and 5-isopropyl-2-methylaniline (127 mg, 0.85 mmol) is further added dropwise thereto. After the reaction mixture is allowed to react for 16 hours at room temperature, TLC is performed to determine the completion of the reaction. The reaction mixture is concentrated under reduced pressure and extracted with water and ethyl acetate. The organic layer is dried with dry sodium sulfate. Column chromatography (EA:n-Hex=1:2) is carried out to obtain 170 mg of the target compound (yield: 81%). 1H NMR (400 MHz, DMSO-d6) delta ppm 12.37 (s, 1H) 9.91 (s, 1H) 7.56 (d, J=7.28 Hz, 1H) 7.47 (d, J=7.16 Hz, 1H) 7.43 (s, 1H) 7.14 (m, 3H) 6.95 (d, J=7.64 Hz, 1H) 4.02 (s, 2H) 2.82 (q, J=7.01 Hz, 1H) 2.20 (s, 2H) 1.17 (s, 3H) 1.15 (s, 3H) |
81% |
With triethylamine; HATU; In acetonitrile; at 20℃;Inert atmosphere; |
A mixture of <strong>[13570-08-6]2-(1H-benzo[d]imidazol-2-yl)acetic acid</strong> 46 (100 mg, 0.57 mmol), 5-isopropyl-2-methylaniline 47, HATU (433 mg, 1.14 mmol), and Et3N (160 muL, 1.14 mmol) in MeCN (7 mL) was stirred at room temperature for 4 h. And then, isopropyl-2-methylaniline (127 mg, 0.85 mmol) was added. After stirring at room temperature for 12 h, the mixture was extracted with EtOAc (3 ~ 30 mL) and washed with H2O (~ 30 mL). The organic layer was dried over anhydrous MgSO4, and concentrated in vacuo to yield the title product 48 (170 mg, 81%); 1H NMR (400 MHz, DMSO-d6) delta ppm 12.37 (br s, 1H) 9.91 (s, 1H) 7.56 (d, J = 7.2 Hz, 1H) 7.47 (d, J = 7.2 Hz, 1H) 7.43 (s, 1H) 7.14 (m, 3H) 6.95 (d, J = 7.6 Hz, 1H) 4.02 (s, 2H) 2.82 (m, 1H) 2.20 (s, 3H) 1.17 (s, 3H) 1.15 (s, 3H); LC/MS (ESI+, MeCN/H2O): m/z: calcd for C19H22N3O: 308.17 [M + H]+; found: 308.2. |