反応 #72806

反応方程式

1-(bromomethyl)-2,3-dichlorobenzene

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

potassium carbonate

→

desired product

収率 6.1%

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

収率 6.1%

溶媒

N,N-Dimethylformamide

反応条件

後処理

1. 1
   その他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
   その他The precipitate formed
7. 7
   ろ過was collected by filtration and air
8. 8
   その他dried
9. 9
   その他to give crude product (2.2 g, 4.51 mmol, 99% yield) (91% pure)
10. 10
    その他A portion of this material (230 mg) was purified by reverse phase-HPLC (25 to 95% AcCN in water, plus 0.1% TFA)

実験手順

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]+.

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