反应 #72806

反应方程式

1-(bromomethyl)-2,3-dichlorobenzene

methyl 5-(4-morpholinyl)-2-(trifluoromethyl)-1H-benzimidazole-7-carboxylate

potassium carbonate

→

desired product

收率 6.1%

methyl 1-[(2,3-dichlorophenyl)methyl]-6-(4-morpholinyl)-2-(trifluoromethyl)-1H-benzimidazole-4-carboxylate

收率 6.1%

溶剂

N,N-Dimethylformamide

反应条件

后处理

1. 1
   其他prepared
2. 2
   温度the mixture was warmed to 80° C.
3. 3
   workup.STIRRINGstirred for 3 h at this temperature
4. 4
   温度The resulting mixture was cooled to rt
5. 5
   workup.ADDITIONpoured over ice
6. 6
   其他The precipitate formed
7. 7
   过滤was collected by filtration and air
8. 8
   其他dried
9. 9
   其他to give crude product (2.2 g, 4.51 mmol, 99% yield) (91% pure)
10. 10
    其他A portion of this material (230 mg) was purified by reverse phase-HPLC (25 to 95% AcCN in water, plus 0.1% TFA)

实验过程

A mixture of methyl 5-(4-morpholinyl)-2-(trifluoromethyl)-1H-benzimidazole-7-carboxylate, prepared as described in Example 45 (1.5 g, 4.56 mmol) and potassium carbonate (1.889 g, 13.67 mmol) in N,N-Dimethylformamide (DMF) (10 mL) was stirred at rt for 10 min. After addition of 1-(bromomethyl)-2,3-dichlorobenzene (1.639 g, 6.83 mmol), the mixture was warmed to 80° C. and stirred for 3 h at this temperature. The resulting mixture was cooled to rt and poured over ice. The precipitate formed was collected by filtration and air dried to give crude product (2.2 g, 4.51 mmol, 99% yield) (91% pure). A portion of this material (230 mg) was purified by reverse phase-HPLC (25 to 95% AcCN in water, plus 0.1% TFA) to give the desired product (137.4 mg, 0.276 mmol, 6.05% yield). 1H NMR (400 MHz, DMSO-d6) δ ppm 7.65 (d, J=2.27 Hz, 1H), 7.61 (dd, J=8.08, 1.26 Hz, 1H), 7.48 (d, J=2.27 Hz, 1H), 7.24 (t, J=7.96 Hz, 1H), 6.25 (dd, J=7.83, 1.26 Hz, 1H), 5.77 (s, 2H), 3.93 (s, 3H), 3.68-3.81 (m, 4H), 3.13-3.24 (m, 4H). MS (ES+) m/e 488 [M+H]+.

来源