Реакция #72806

Уравнение реакции

1-(bromomethyl)-2,3-dichlorobenzene

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

potassium carbonate

→

desired product

Выход 6.1%

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

Выход 6.1%

Растворители

N,N-Dimethylformamide

Условия реакции

Обработка

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

Методика

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]+.

Источник