تفاعل #57454

معادلة التفاعل

(2S)-4-Amino-4-oxo-2-[(2-quinolinylcarbonyl)amino]butanamido N-(1S,2R)-1-benzyl-3-[(cyclopentyloxy)-amino]-2-hydroxypropylcarbamate

(2S)-4-Amino-4-oxo-2-[(2-quinolinylcarbonyl)amino]butanamido N-(1S,2R)-1-benzyl-3-[(cyclopentyloxy)amino]-2-hydroxypropylcarbamate

methyl N-[5-(chlorosulfonyl)-1H-benzimidazol-2-yl]carbamate

diisopropylethylamine

→

desired product

المردود 17.0%

(2S)-4-Amino-4-oxo-2-[(2-quinolinylcarbonyl)amino]butanamido N-(1S,2R)-1-benzyl-3-[(cyclopentyloxy)(2-{(methoxycarbonyl)amino]-1H-benzimidazol-5-ylsulfonyl)amino]-2-hydroxypropylcarbamate

المردود 17.0%

المذيبات

tetrahydrofuran

methanol

ظروف التفاعل

المعالجة

1. 1
   تركيزconcentrated in vacuo
2. 2
   workup.ADDITIONEthyl acetate (30 mL) and water (10 mL) were added
3. 3
   أخرىthe layers were separated
4. 4
   غسيلThe organic layer was washed with brine (10 mL)
5. 5
   تجفيفdried over anhydrous sodium sulfate
6. 6
   ترشيحfiltered
7. 7
   تركيزconcentrated in vacuo
8. 8
   أخرىThe residue was purified by preparative silica gel

الإجراء التجريبي

(2S)-4-Amino-4-oxo-2-[(2-quinolinylcarbonyl)amino]butanamido N-(1S,2R)-1-benzyl-3-[(cyclopentyloxy)-amino]-2-hydroxypropylcarbamate (Step 1, above), (44 mg, 0.0825 mmol), methyl N-[5-(chlorosulfonyl)-1H-benzimidazol-2-yl]carbamate (24 mg, 0.0825 mmol), and anhydrous diisopropylethylamine (0.05 mL, 0.280 mmol) were combined in anhydrous tetrahydrofuran (3 mL) in a 25 mL round bottomed flask under nitrogen. The reaction was stirred for 24 hours and concentrated in vacuo. Ethyl acetate (30 mL) and water (10 mL) were added and the layers were separated. The organic layer was washed with brine (10 mL), dried over anhydrous sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by preparative silica gel TLC using 90:10 chloroform:methanol as an eluent to provide the desired product as a white solid (11 mg, 0.014 mmol, 17%). 1HNMR (d6-DMSO) δ: 8.86 (d, J=8.4 Hz, 1H), 8.62 (d, J=8.4 Hz, 1H), 8.22-6.94 (m, 12H), 5.19 (d, J=6.2 Hz, 1H), 4.77-4.72 (m, 2H), 4.02-1.35 (m, 17H), 3.80 (s, 3H). MS(ES): 787 (M+1), 785 (M−1).

المصدر