Reaction #11674

Reaction equation

Diisopropylethylamine

(R)-3-amino-1-carbomethoxymethyl-3,4-dihydrocarbostyril hydrochloride

5-chloroindole-2-carboxylic acid

1-hydroxy-7-azabenzotriazole

1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride

→

title compound

Yield 26.3%

(R)-1-carbomethoxymethyl-3-(5-chloroindole-2-carbonylamino)-3,4-dihydrocarbostyril

Yield 26.3%

Solvents

ethyl acetate

tetrahydrofuran

Conditions

Workup

1. 1
   Otherformed
2. 2
   Washwashed sequentially with 1.0 M aqueous hydrochloric acid (25 mL twice), 1.0 M aqueous sodium hydroxide (20 mL) and brine (20 mL)
3. 3
   Dryingdried over anhydrous sodium sulfate
4. 4
   Otherevaporated under vacuum
5. 5
   OtherOne half of the residue was purified by reverse phase preparative HPLC

Procedure

Alternatively, (R)-3-amino-1-carbomethoxymethyl-3,4-dihydrocarbostyril hydrochloride (19 mg) was added to a mixture of tetrahydrofuran (10 mL), 5-chloroindole-2-carboxylic acid (15 mg), 1-hydroxy-7-azabenzotriazole (12 mg), and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (16 mg) at room temperature. Diisopropylethylamine (19 mg) was added, and the resulting yellow suspension was stirred under argon for 16 h, during which a solution formed. The solution was diluted with ethyl acetate (50 mL) and washed sequentially with 1.0 M aqueous hydrochloric acid (25 mL twice), 1.0 M aqueous sodium hydroxide (20 mL) and brine (20 mL), dried over anhydrous sodium sulfate and evaporated under vacuum. One half of the residue was purified by reverse phase preparative HPLC to provide the title compound (7.6 mg).

Source