반응 #11693

반응 방정식

Diisopropylethylamine

5-chloroindole-2-carboxylic acid

1-hydroxy-7-azabenzotriazole

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

(R)-4-amino-2, 3,4,5-tetrahydro-2-benzazepin-3 (1H)-one hydrochloride salt

→

title compound

수율 44.0%

(R)-4-(5-chloroindole-2-carbonylamino)-2,3,4,5-tetrahydro-2-benzazepin-3(1H)-one

수율 44.0%

용매

tetrahydrofuran

반응 조건

후처리

1. 1
   기타formed
2. 2
   기타The solution was evaporated under vacuum
3. 3
   workup.DISSOLUTIONthe residue was redissolved in ethyl acetate (100 mL)
4. 4
   세척This was washed sequentially with 1.0 M aqueous hydrochloric acid (50 mL), 1.0 M aqueous sodium hydroxide (50 mL), water (50 mL) and brine (50 mL)
5. 5
   건조dried over anhydrous sodium sulfate
6. 6
   기타evaporated under vacuum
7. 7
   기타The resulting solid crude product was triturated with 20% methanol in diethyl ether (20 mL four times)
8. 8
   기타Drying under vacuum

실험 절차

(R)-4-amino-2, 3,4,5-tetrahydro-2-benzazepin-3 (1H)-one hydrochloride salt (387 mg) (amine free base prepared in U.S. Pat. No. 5,545,735) was added to a mixture of tetrahydrofuran (40 mL), 5-chloroindole-2-carboxylic acid (356 mg), 1-hydroxy-7-azabenzotriazole (272 mg), and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (382 mg) at room temperature. Diisopropylethylamine (202 mg) was added, and the resulting yellow suspension was stirred under argon for 16 h, during which a solution formed. The solution was evaporated under vacuum and the residue was redissolved in ethyl acetate (100 mL). This was washed sequentially with 1.0 M aqueous hydrochloric acid (50 mL), 1.0 M aqueous sodium hydroxide (50 mL), water (50 mL) and brine (50 mL), dried over anhydrous sodium sulfate, and evaporated under vacuum. The resulting solid crude product was triturated with 20% methanol in diethyl ether (20 mL four times). Drying under vacuum provided pure title compound (283 mg). HPLC/MS [M+H]+, 354.

출처