3-苯氧基-1-丙胺盐酸盐

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: A flask containing 1-(4-bromophenyl)-N-pyridin-3-ylmethyl-1H-benzimidazole-5-carboxamide (EXAMPLE C2, 100 mg, 0.25 mmol) and 3-phenoxypropylamine hydrochloride (54 mg, 0.29 mmol) was evacuated and refilled with N2 (2×). To this was added BINAP (112 mg, 0.18 mmol), Pd2 dba3 (55 mg, 0.06 mmol) and t-BuONa (68 mg, 0.7 mmol) in one portion as a mixture, with minimum exposure to air. The flask was again evacuated and refilled with N2 (3×). Degassed, anhydrous dioxane (2 mL) was added via syringe and the solution was stirred under N2 for 10 min at rt and then at 80° C. for 18 h. Later, the reaction was cooled to rt, filtered through Celite (using MeOH and CH2Cl2 to rinse the Celite), concentrated under reduced pressure and purified using the Waters mass-directed HPLC purification system to provide 1-{4-[(3-phenoxypropyl)amino]phenyl}-N-pyridin-3-ylmethyl-1H-benzimidazole-5-carboxamide as a white solid. MS (ES+): m/z 478 (100) [MH+]. was evacuated refilled with N2 (2×) The flask was again evacuated refilled with N2 (3×) Degassed anhydrous dioxane (2 mL) was added via syringe at 80° C. for 18 h Later, the reaction was cooled to rt filtered through Celite ( to rinse the Celite), concentrated under reduced pressure purified the Waters mass-directed HPLC purification system

反应条件: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

实验步骤: Methyl chloro(oxo)acetate (1.77 mL) was added to a stirred solution of (3-phenoxypropyl)amine hydrochloride (3000 mg) and pyridine (2.98 mL) in DCM (100 mL) at 0° C. After the addition was complete the solution was allowed to warm to ambient temperature and stirred for 16 hours. Water (50 mL) was added and the mixture was extracted with DCM (2×75 mL). The organic extracts were combined, washed with brine (50 mL), dried and concentrated in vacuo to give an oil. This was purified by flash chromatography on a 90 g Biotage™ silica column using a gradient of 10-60% EtOAc in hexane as the eluent to give methyl oxo[(3-phenoxypropyl)amino]acetate (3212 mg) as a solid; 1H NMR δ (CDCl3) 7.60 (1H, bs), 7.28 (2H+CHCl3, m), 6.94 (3H, m), 4.07 (2H, t), 3.90 (3H, s), 3.58 (2H, quartet), 2.08 (2H, m), +0.1 mole of EtOAc; MS m/e MH+ 238. After the addition the mixture was extracted with DCM (2×75 mL) washed with brine (50 mL) dried concentrated in vacuo to give an oil This was purified by flash chromatography on a 90 g Biotage™ silica column