Reaction #539343

Reaction equation

(E)-1-[11-(1-Cyanoethylidene)-6,11-dihydrodibenzo[b,e]oxepin-8-yl]methyl-2-propylbenzimidazole-4-carboxylic acid

sodium hydrogen carbonate

2-aminoethanol

1-ethyl-3-(3-dimethylaminopropyl)carbodiimide

1-hydroxybenzotriazole

→

(E)-N-(2-hydroxyethyl) 1-[11-(1-cyanoethylidene)-6,11-dihydrodibenzo[b,e]oxepin-8-yl]methyl-2-propylbenzimidazole-4-carboxamide

Yield 99.1%

Solvents

DMF

Conditions

Workup

1. 1
   Filtrationthe precipitated solid was collected by filtration
2. 2
   OtherThe residue was purified by silica gel column chromatography (chloroform/methanol=99/1 to 95/5)

Procedure

[step 1] (E)-1-[11-(1-Cyanoethylidene)-6,11-dihydrodibenzo[b,e]oxepin-8-yl]methyl-2-propylbenzimidazole-4-carboxylic acid (220 mg, 0.48 mmol) obtained in Example 100, step 2 was dissolved in DMF (4.0 mL), 2-aminoethanol (57 μL, 0.95 mmol), 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (109 mg, 0.57 mmol) and 1-hydroxybenzotriazole (87 mg, 0.57 mmol) were added, and the mixture was stirred at room temperature for 15 hr. Saturated aqueous sodium hydrogen carbonate solution (15 mL) was added to the mixture, and the precipitated solid was collected by filtration. The residue was purified by silica gel column chromatography (chloroform/methanol=99/1 to 95/5) to give (E)-N-(2-hydroxyethyl) 1-[11-(1-cyanoethylidene)-6,11-dihydrodibenzo[b,e]oxepin-8-yl]methyl-2-propylbenzimidazole-4-carboxamide (241 mg, 99%). [step 2] Using (E)-N-(2-hydroxyethyl) 1-[11-(1-cyanoethylidene)-6,11-dihydrodibenzo[b,e]oxepin-8-yl]methyl-2-propylbenzimidazole-4-carboxamide (240 mg, 0.47 mmol) obtained in step 1 and in the same manner as in Example 5, the title compound (compound 102) (70 mg, 26%) was obtained.

Source