تفاعل #72806

معادلة التفاعل

1-(bromomethyl)-2,3-dichlorobenzene

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

potassium carbonate

→

desired product

المردود 6.1%

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

المردود 6.1%

المذيبات

N,N-Dimethylformamide

ظروف التفاعل

المعالجة

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

الإجراء التجريبي

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]+.

المصدر