تفاعل #42293

معادلة التفاعل

HOBt

EDC

1-carboxy-5-piperdinylglutaramide

3-(aminocarbonyl)-5-[(dipropylamino)carbonyl]benzoic acid

1-9H-fluoren-9-ylmethyl(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl(3-iodobenzyl)carbamate hydrochloride

NMM

→

title compound

1-9H-fluoren-9-ylmethyl(2R,3S)-4-(3,5-difluorophenyl)-2-hydroxy-3-{[5-oxo-5-(1-piperidinyl)pentanoyl]amino}butyl(3-iodobenzyl)carbamate

المذيبات

DMF

ظروف التفاعل

المعالجة

1. 1
   تركيزthen concentrated under reduced pressure
2. 2
   أخرىThe residue is partitioned between ethyl acetate and saturated aqueous bicarbonate
3. 3
   غسيلThe organic phases are washed with aqueous potassium bisulfate, saline
4. 4
   تجفيفdried over sodium sulfate
5. 5
   تركيزfinally concentrated under reduced pressure
6. 6
   أخرىto give crude product
7. 7
   أخرىPurification via flash chromatography with ethyl acetate/hexane (50/50)

الإجراء التجريبي

HOBt (81 mg, 0.6 mmole) and EDC (105 mg, 0.55 mmole) are added to 1-carboxy-5-piperdinylglutaramide (IX, 100 mg, 0.5 mmole) in DMF (2 ml). The acid is activated 60 minutes then treated with 1-9H-fluoren-9-ylmethyl(2R,3S)-3-amino-4-(3,5-difluorophenyl)-2-hydroxybutyl(3-iodobenzyl)carbamate hydrochloride (XXXV, EXAMPLE 590, 300 mg, 0.43 mmole) and NMM (0.19 ml, 1.72 mmole). The reaction is stirred 3 hours then concentrated under reduced pressure. The residue is partitioned between ethyl acetate and saturated aqueous bicarbonate. The organic phases are washed with aqueous potassium bisulfate, saline, dried over sodium sulfate and finally concentrated under reduced pressure to give crude product. Purification via flash chromatography with ethyl acetate/hexane (50/50) then methanol/ethyl acetate (10/90) gives the title compound, M+H=838.

المصدر