| 75.4% |
With ammonium chloride; N-ethyl-N,N-diisopropylamine; HATU; In N,N-dimethyl-formamide; at 20℃; for 4h; |
To a stirred solution of compound 0419-1 (2.0 g, 9.3 mmol) in DMF (25 ml) was added (2173) NH4CI (497 mg, 9.3 mmol), HATU (5.3 g, 13.95 mmol), and DIEA (3.6 g, 27.9 mmol) was stirred at rt for 4 h. Then added water, the aqueous phase was extracted with dichloromethane, the combined organic phases were dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo , purified by C.C. to give 419-2 (1.5 g, yield: 75.4%) as a white solid. |
|
|
Example 1 Synthesis of 2-(3-bromophenyl)acetamide 1-Hydroxybenzotriazole (HOBT, 13.82 g, 102.3 mmol), N-ethyldiisopropyl amine (Hunig's base, 13.22 g, 102.3 mmol) and ammonium carbonate (27.0 g, 279.0 mmol) were added to a solution of (3-bromophenyl)acetic acid (20.0 g, 93.0 mmol) in freshly dried and distilled tetrahydrofuran (80 mL) under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for about 5 minutes and then cooled to 0 C and stirred at the same temperature for about 1 hour. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI.HCl, 19.61 g, 102.3 mmol) was added at 0 C under nitrogen atmosphere. The reaction mixture was stirred at room temperature for about 12 hours. The solvent was evaporated under vacuum and water was added. A white solid was obtained which was filtered, washed with water and dried. Yield: 12.69 g. 1H NMR (400 MHz, DMSO-d6): δ 7.52 (brs, 1H, -NH), 7.46 (s, 1H, Ar-H), 7.43-7.40 (m, 2H, Ar-H), 7.25-7.18 (m, 2H, Ar-H), 6.95 (brs, 1H, -NH) and 3.34 (s, 2H, -CH2). Mass Spectrum (m/z, +ve ion mode): 214 [M++1] |
|
|
1-Hydroxybenzotriazole (HOBT, 13.82 g, 102.3 mmol), N-ethyldiisopropyl amine (Hunig's base, 13.22 g, 102.3 mmol) and ammonium carbonate (27.0 g, 279.0 mmol) were added to a solution of (3-bromophenyl)acetic acid (20.0 g, 93.0 mmol) in freshly dried and distilled tetrahydrofuran (80 ml) under a nitrogen atmosphere. The reaction mixture was stirred at room temperature for about 5 min and then cooled to 0 C. and stirred at the same temperature for about 1 hour. 1-(3-Dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (EDCI.HCl, 19.61 g, 102.3 mmol) was added to it at 0 C. under nitrogen atmosphere. The reaction mixture was stirred at room temperature for about 12 hours. The solvent was evaporated under vacuum and water was added to it. A white solid was obtained which was filtered, washed with water and dried. Yield: 12.69 g. 1H NMR (400 MHz, DMSO-d6): δ 7.52 (brs, 1H, -NH), 7.46 (s, 1H, Ar-H), 7.43-7.40 (m, 2H, Ar-H), 7.25-7.18 (m, 2H, Ar-H), 6.95 (brs, 1H, -NH) and 3.34 (s, 2H, -CH2). Mass Spectrum (m/z, +ve ion mode): 214 [M++1] |
Chemistry
Pharmaceutical Intermediates
Inhibitors/Agonists
Material Science
For Research Only
120K+ Compounds
Competitive Price
1-2 Day Shipping
