تفاعل #58582

معادلة التفاعل

acid 4

2(R)-cyclopentylmethyl-3 (S)-hydroxyl-5-phenylpentanoic acid

3-amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one p-toluenesulfonate salt

1-Hydroxy-benzotriazole hydrate

triethylamine

→

3-(2(R)-Cyclopentylmethyl-3 (S)-hydroxyl-1-oxo-5-phenylpentyl)amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one

المذيبات

ethyl acetate

methylene chloride

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGAfter the mixture was stirred for 16 h
2. 2
   غسيلThe organic layer was washed with 1 M HCl (15 mL), 5% NaHCO3 (30 mL) and brine (30 mL)
3. 3
   تجفيفdried over anhydrous magnesium sulfate
4. 4
   تركيزconcentrated under reduced pressure
5. 5
   أخرىPurification by chromatotron (30% ethyl acetate-hexane)
6. 6
   أخرىafforded two diastereomers A and B

الإجراء التجريبي

A mixture of acid 4 (250 mg, 0.900 mmol) and 3-amino-1-methyl-5-phenyl-2,3-dihydro-1H-1,4-benzodiazepin-2-one p-toluenesulfonate salt (364 mg, 0.820 mmol) in 4 mL of methylene chloride was stirred at 0° C. 1-Hydroxy-benzotriazole hydrate (133 mg, 0.980 mmol), 1-[3-(dimethylamine)propyl]-3-ethylcarbodiimide hydrochloride (314 mg, 1.64 mmol) and triethylamine (0.51 mL, 3.7 mmol) were added sequentially. After the mixture was stirred for 16 h, 30 mL of ethyl acetate was added. The organic layer was washed with 1 M HCl (15 mL), 5% NaHCO3 (30 mL) and brine (30 mL), dried over anhydrous magnesium sulfate and concentrated under reduced pressure. Purification by chromatotron (30% ethyl acetate-hexane) afforded two diastereomers A and B. A: 120 mg (25%); 1H NMR (300 MHz, CDCl3) δ 7.20-7.70 (15H, m), 5.54 (1H, d, J=8.0 Hz), 4.02 (1H, m), 3.48 (3H, s), 2.83-3.00 (1H, m), 2.62-2.74 (1H, m), 2.40-2.48 (1H, m), 1.00-2.00 (13H, m); MS (ESI): 524 (M+H), 546 (M+Na), 522 (M−H), 558 (M+Cl). B: 120 mg (25%); 1H NMR (300 MHz, CDCl3) δ 7.60 (1H, d, J=6.9 Hz), 7.20-7.45 (14H, m), 5.56 (1H, d, J=8.4 Hz), 3.84 (1H, m), 3.48 (3H, s), 2.83-3.00 (1H, m), 2.62-2.74 (1H, m), 2.50-2.60 (1H, m), 1.00-1.95 (13H, m); MS (ESI): 524 (M+H), 546 (M+Na), 522 (M−H).

المصدر