تفاعل #53516

معادلة التفاعل

2-Chloro-N-methylpyridinium iodide

N-(4-methoxy-thiobenzoyl)acetamide

2-amino-N-(4-cyano-1-methyl-piperidin-4-yl)-3-cyclohexyl-propionamide bis hydrochloride salt

N,N-diisopropylethylamine

→

desired product

2-{[Acetylimino-(4-methoxy-phenyl)-methyl]-amino}-N-(4-cyano-1-methyl-piperidin-4-yl)-3-cyclohexyl-propionamide

المذيبات

dichloromethane

dichloromethane

ظروف التفاعل

المعالجة

1. 1
   غسيلwashed with 2×150 mL of saturated sodium bicarbonate
2. 2
   تجفيفThe organic phase was dried (MgSO4)
3. 3
   تركيزconcentrated
4. 4
   أخرىThe resulting residue was chromatographed over 100 g of flash silica first using EtOAc

الإجراء التجريبي

2-Chloro-N-methylpyridinium iodide (660 mg, 2.58 mmol), was added to a solution of N-(4-methoxy-thiobenzoyl)acetamide (420 mg, 2.01 mmol), 2-amino-N-(4-cyano-1-methyl-piperidin-4-yl)-3-cyclohexyl-propionamide bis hydrochloride salt (730 mg, 2.00 mmol), and N,N-diisopropylethylamine (1.05 mL, 6.02 mmol) in dichloromethane (8.0 mL). The reaction mixture was stirred at room temperature for 2 h, then diluted with dichloromethane (100 mL)and washed with 2×150 mL of saturated sodium bicarbonate. The organic phase was dried (MgSO4) and concentrated. The resulting residue was chromatographed over 100 g of flash silica first using EtOAc, then dichloromethane/methanol 9:1 as the eluant to provide the desired product as an off white solid (377 mg, 40%). 1H NMR (400 MHz, DMSO-d6) δ 0.70-0.90 (m, 2H), 1.00-1.30 (m, 4H), 1.35-1.65 (m, 8H), 1.72 (s, 3H), 1.85-2.20 (m, 6H), 2.48-2.60 (m, 1H), 3.78 (s, 3H), 4.20-4.35 (m, 1H), 6.95-6.99 (m, 2 H), 7.33 (d, J=8.4 Hz, 1H), 7.72 (d, J=8.4 Hz, 1H). MS, m/z 468=M+1.

المصدر