반응 #577183

반응 방정식

1-Methyl-5-[4′-(trifluoromethyl)[1,1′-biphenyl]-2-carboxamido]-1H-indole-2-carboxylic acid sodium salt

(S)-N-benzyl-N-methyl-2-phenylglycinamide hydrochloride

1-hydroxybenzotriazole hydrate

3-(dimethylamino)propyl-N′-ethylcarbodimide hydrochloride

methanesulfonic acid

→

(S)-N-{2-[benzyl(methyl)amino]-2-oxo-1-phenylethyl}-1-methyl-5-[4′-(trifluoromethyl)[1,1′-biphenyl]-2-carboxamido]-1H-indole-2-carboxamide

용매

dichloromethane

dichloromethane

Triethylamine

triethylamine

반응 조건

후처리

1. 1
   workup.ADDITIONwas added slowly
2. 2
   온도to warm to room temperature overnight
3. 3
   workup.WAITAfter approximately 2 hours
4. 4
   세척the mixture was twice washed with saturated aqueous sodium hydrogen carbonate (2×200 mL)
5. 5
   세척once washed with 0.5M aqueous hydrochloric acid solution (200 mL)
6. 6
   세척once washed with demineralized water (200 mL)

실험 절차

1-Methyl-5-[4′-(trifluoromethyl)[1,1′-biphenyl]-2-carboxamido]-1H-indole-2-carboxylic acid sodium salt (16.0 g), from step (d) alternative A, methanesulfonic acid (2.24 mL), 1-hydroxybenzotriazole hydrate (5.32 g) and N-[3-(dimethylamino)propyl-N′-ethylcarbodimide hydrochloride (8.66 g) were combined in dichloromethane (384 mL) at 0-5° C. and the mixture stirred for 1 hour. Triethylamine (4.78 ml mL) was added followed by a slurry of (S)-N-benzyl-N-methyl-2-phenylglycinamide hydrochloride (11.1 g), from step (e), in dichloromethane (48 mL) was added slowly, maintaining 0-5° C. The resulting slurry was allowed to warm to room temperature overnight. Further triethylamine (2.4 mL) was added at 0° C. After approximately 2 hours, the mixture was twice washed with saturated aqueous sodium hydrogen carbonate (2×200 mL), once washed with 0.5M aqueous hydrochloric acid solution (200 mL) and once washed with demineralized water (200 mL) adjusting to pH=6 with aqueous sodium hydrogen carbonate solution, providing a dichloromethane solution of (S)-N-{2-[benzyl(methyl)amino]-2-oxo-1-phenylethyl}-1-methyl-5-[4′-(trifluoromethyl)[1,1′-biphenyl]-2-carboxamido]-1H-indole-2-carboxamide.

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