With the rapid development and complex challenges of chemical substances, new drug synthesis pathways are usually the most effective.69999-16-2,2,3-Dihydrobenzofuranyl-5-acetic acid,as a common compound, the synthetic route is as follows.
Step 3. 2~(2,3-dihydro-l~benzofuran-5-ylmethyl)-l-(3-rnethylbutyl)-N,N-bis(2,2,2-trifluoro- ethyI)-lH-benzimidazole-5-carboxamide[0168] To a mixture of 3-amino-4-[(3-methylbutyl)amino]-N,N-bis(2,2,2- trifluoroethyl)benzamide (Step 2 of the Example 1, 0.175g, 0.454 mmol, lequiv), 2,3-dihydro-l- benzofuran-5-ylacetic acid (0.089g, 0.50 mmol, 1.1 equiv) and HATU (0.19Og, 0.500 mmol, 1.1 equpsiloniv) was added a solution of DIPEA (160 muL, 0.92 mmol, 2equiv) in DMF (5 mL). The mixture was stirred overnight at room temperature. Complete consumption of the starting material was confirmed by LC-MS. DMF was removed under reduced pressure. Ethyl acetate was added to the resulting residue. The organic layer was washed once with a saturated aqueous <n=”54″/>NaHCtheta3 solution, once with brine and dried over anhydrous Na2SO4. Ethyl acetate was removed under reduce pressure. The resulting residue was dissolved in dichloroethane and a few drops of concentrated HCl were added. The mixture was stirred at 80 C for 3 hours. Complete consumption of the starting material was confirmed by LC-MS. Dichloromethane was added. The organic layer was washed once with a 2M aqueous NaOH solution, once with brine and dried over anhydrous Na2SO4. Dichloromethane was removed under reduced pressure. The resulting residue was purified by column chromatography on silica gel (hexanes/EtOAc, 50:50) to afford 2-(2,3-dmydro-l-benzofuran-5-ylmethyl)-l-(3-methylbutyl)-N,N-bis(2,2,2-trifluoro- ethyl)-lH-benzimidazole-5-carbochiamide (0.173 mg) in 72% yield. The product was dissolved in methanol (about 5 mL) and 1 equivalent of TFA was added. The mixture was stirred at room temperature for about 30 minutes. Methanol was removed under reduced pressure. Water was added and the resulting residue was lyophilized to afford 2-(2,3-dihydro-l-benzofuran-5- ymiethyl)-l-(3-me1hylbu1yl)-N,N-bis(2,2,2-trifluoro-e&yl)-lH-benzimidazole-5-carboxamide as the corresponding TFA salt. 1H NMR (400 MHz, METHANOL-D4) 6 ppm 0.96 (d, /=6.64 Hz, 6 H) 1.45 – 1.54 (m, 2 H) 1.63 – 1.75 (m, 1 H) 3.18 (t, /=8.79 Hz, 2 H) 4.32 – 4.44 (m, 6 H) 4.49 (s, 2 H) 4.54 (t, J=8.79 Hz, 2 H) 6.75 (d; /=8.20 Hz, 1 H) 7.07 (dd, J=8.20, 1.95 Hz, 1 H) 7.20 (s, 1 H) 7.58 (dd, /=8.50, 1.46 Hz, 1 H) 7.79 (d, /=0.78 Hz, 1 H) 7.87 (d, /=8.59 Hz, 1 H); MS (ESI) m/z 527.8 (MHhH)+; Anal. Calcd (%) for C26H27F6N3O2 + 1.0 TFA: C, 52.42; H, 4.40; N, 6.55. Found: C, 52.52; H, 4.27; N 6.18.
As the paragraph descriping shows that 69999-16-2 is playing an increasingly important role.
Reference£º
Patent; ASTRAZENECA AB; WO2007/91950; (2007); A1;,
Benzofuran – Wikipedia
Benzofuran | C8H6O – PubChem