Reaction #11670

Reaction equation

Diisopropylethylamine

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

5-chloroindole-2-carboxylic acid

1-hydroxy-7-azabenzotriazole

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

→

title compound

Yield 81.2%

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

Yield 81.2%

Solvents

ethyl acetate

tetrahydrofuran

Conditions

Workup

1. 1
   Otherformed
2. 2
   Washwashed sequentially with 1.0 M aqueous hydrochloric acid (25 mL), 1.0 M aqueous sodium hydroxide (25 mL), and brine (25 mL)
3. 3
   Dryingdried over anhydrous sodium sulfate
4. 4
   Otherevaporated under vacuum
5. 5
   OtherThe resulting solid crude product was triturated with diethyl ether (5 mL twice), then 50% methanol in diethyl ether (5 mL twice)
6. 6
   OtherDrying under vacuum

Procedure

Alternatively, (R)-3-amino-3,4-dihydrocarbostyril hydrochloride (95 mg) was added to a mixture of tetrahydrofuran (10 mL), 5-chloroindole-2-carboxylic acid (103 mg), 1-hydroxy-7-azabenzotriazole (85 mg), and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (120 mg) at room temperature. Diisopropylethylamine (186 mg) was added, and the resulting yellow suspension was stirred for 2 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), 1.0 M aqueous sodium hydroxide (25 mL), and brine (25 mL), dried over anhydrous sodium sulfate, and evaporated under vacuum. The resulting solid crude product was triturated with diethyl ether (5 mL twice), then 50% methanol in diethyl ether (5 mL twice). Drying under vacuum provided pure title compound (132 mg).

Source