Diisopropylethylamine → N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-propyl-1,2-benzisoxazole-5-carboxamide

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Reaction Steps

To a stirred solution of 3-propyl-1,2-benzisoxazole-5-carboxylic acid (70 mg, 0.3 mmol) and HATU (130 mg, 0.3 mmol) in methylene chloride (5 mL) was added N,N-diisopropylethylamine (110 μL, 0.6 mmol). In a separate flask, N,N-diisopropylethylamine (110 μL, 0.6 mmol) was added to (2R,3S)-3-amino-4-(3,5-difluorophenyl)-1-[(3-ethylbenzyl)amino]butan-2-ol (EXA xxx)(140 mg, 0.3 mmol) in methylene chloride (2 mL). This solution was added to the above solution containing the acid and the resulting reaction mixture was stirred at room temperature for 18 h. The reaction mixture was partitioned between methylene chloride and water. The organic layer was washed with water, dried (sodium sulfate), filtered, and concentrated under reduced pressure to afford a crude oil. Purification by flash column chromatography (silica, gradient 97:3 to 94:6 methylene chloride/methanol) provided N-{(1S,2R)-1-(3,5-difluorobenzyl)-3-[(3-ethylbenzyl)amino]-2-hydroxypropyl}-3-propyl-1,2-benzisoxazole-5-carboxamide (30 mg). ESI-MS m/z 522 [M+H]+

Provenance & Evidence