Reaction #1145568

Reaction equation

Diisopropylethylamine

3-bromo-4-(methoxycarbonyl)benzoic acid

O-(benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate

1H-indole-4-methanamine hydrochloride salt

1H-indole-4-methanamine hydrochloride

1-hydroxybenzotriazole

→

2-bromo-4-[[[(1H-indol-4-yl)methyl]amino]carbonyl]benzoic acid methyl ester

Yield 70.0%

Solvents

N,N-dimethylformamide

Conditions

Workup

1. 1
   ConcentrationAfter the reaction mixture was concentrated under vacuum
2. 2
   Otherto remove most of the N,N-dimethylformamide
3. 3
   workup.ADDITIONthe residue was diluted with ethyl acetate (50 mL)
4. 4
   Washwashed with 1N hydrochloric acid solution (10 mL), water (10 mL), saturated aqueous sodium bicarbonate solution (10 mL) and brine (10 mL)
5. 5
   DryingThe organic layer was dried (MgSO4)
6. 6
   Filtrationfiltered
7. 7
   Otherevaporated
8. 8
   Otherthe residue was chromatographed (silica gel, 25-35% ethyl acetate in petroleum ether)

Procedure

Diisopropylethylamine (2.3 mL, 13.2 mmol) was added dropwise to a solution of 3-bromo-4-(methoxycarbonyl)benzoic acid (Example 76; 861 mg, 3.32 mmol), O-(benzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (1.39 g, 3.65 mmol), 1H-indole-4-methanamine hydrochloride salt (Example 68; 528 mg, 3.98 mmol) and 1-hydroxybenzotriazole (493 mg, 3.65 mmol) in N,N-dimethylformamide (6.5 mL) at 0° C. The solution was allowed to warm to room temperature and then was stirred for 24 h. After the reaction mixture was concentrated under vacuum to remove most of the N,N-dimethylformamide, the residue was diluted with ethyl acetate (50 mL) and washed with 1N hydrochloric acid solution (10 mL), water (10 mL), saturated aqueous sodium bicarbonate solution (10 mL) and brine (10 mL). The organic layer was dried (MgSO4), filtered, evaporated and the residue was chromatographed (silica gel, 25-35% ethyl acetate in petroleum ether) to provide 2-bromo-4-[[[(1H-indol-4-yl)methyl]amino]carbonyl]benzoic acid methyl ester (900 mg, 70% yield) as an off-white solid.

Source