Reaction #11687

Reaction equation

(S)-3-amino-2,3-dihydro-1,5-benzoxazepin-4(5H)-one hydrochloride salt

5-chloroindole-2-carboxylic acid

1-hydroxy-7-azabenzotriazole

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

diisopropylethylamine

→

title compound

Yield 88.8%

(S)-3-(5-chloroindole-2-carbonylamino)-2,3-dihydro-1,5-benzoxazepin-4(5H)-one

Yield 88.8%

Solvents

tetrahydrofuran

Conditions

Workup

1. 1
   workup.STIRRINGThe resulting yellow suspension was stirred for 30 min, during which a solution
2. 2
   Otherformed
3. 3
   OtherAfter evaporation under vacuum
4. 4
   workup.DISSOLUTIONthe residue was redissolved in ethyl acetate (50 mL)
5. 5
   Washthe resulting solution was washed sequentially with 1.0 M aqueous hydrochloric acid (25 mL), 1.0 M aqueous sodium hydroxide (25 mL), water (25 mL) and brine (25 mL)
6. 6
   Dryingdried over anhydrous sodium sulfate
7. 7
   Otherevaporated under vacuum
8. 8
   OtherThe resulting solid crude product was triturated with diethyl ether (20 mL three times)
9. 9
   Otherby drying under vacuum

Procedure

Alternatively, to a mixture of (S)-3-amino-2,3-dihydro-1,5-benzoxazepin-4(5H)-one hydrochloride salt (54 mg) (prepared in Itoh, et al., Chem. Pharm. Bull. 1986, 34, 1128–1147), tetrahydrofuran (10 mL), 5-chloroindole-2-carboxylic acid (39 mg), 1-hydroxy-7-azabenzotriazole (31 mg), and 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (57 mg) stirring at room temperature under argon was added diisopropylethylamine (65 mg). The resulting yellow suspension was stirred for 30 min, during which a solution formed. After evaporation under vacuum, the residue was redissolved in ethyl acetate (50 mL) and the resulting solution was washed sequentially with 1.0 M aqueous hydrochloric acid (25 mL), 1.0 M aqueous sodium hydroxide (25 mL), water (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 (20 mL three times), followed by drying under vacuum to provide the title compound (63 mg).

Source