تفاعل #49241

معادلة التفاعل

dipropylamine

3-(((1S,2S)-1-((2R,4R)-1-(tert-butoxycarbonyl)-4-propoxypyrrolidin-2-yl)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propan-2-yl)carbamoyl)-5-methylbenzoic acid

Hunig's base

( A )

(2R,4R)-tert-butyl 2-((1S,2S)-2-(3-(benzamido)-5-methylbenzamido)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propyl)-4-propoxypyrrolidine-1-carboxylate

(2R,4R)-tert-butyl 2-((1S,2S)-2-(3-(benzamido)-5-methylbenzamido)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propyl)-4-propoxypyrrolidine-1-carboxylate

HATU

→

title compound

المردود 90.0%

N1-((1R,2S)-3-(3,5-difluorophenyl)-1-hydroxy-1-((2R,4R)-4-propoxypyrrolidin-2-yl)propan-2-yl)-5-methyl-N3,N3-dipropylisophthalamide

المردود 90.0%

المذيبات

dichloromethane

ظروف التفاعل

المعالجة

1. 1
   workup.ADDITIONwas then added
2. 2
   workup.STIRRINGthe reaction mixture was stirred at rt for 6 h
3. 3
   أخرىThe crude mixture was purified by silica gel Flash Chromatography (0% to 10% to 30% EtOAc/Hexane step gradient)

الإجراء التجريبي

Step 10 (A): Preparation of (2R,4R)-tert-butyl 2-((1S,2S)-2-(3-(benzamido)-5-methylbenzamido)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propyl)-4-propoxypyrrolidine-1-carboxylate. To a solution of 3-(((1S,2S)-1-((2R,4R)-1-(tert-butoxycarbonyl)-4-propoxypyrrolidin-2-yl)-1-(tert-butyldimethylsilyloxy)-3-(3,5-difluorophenyl)propan-2-yl)carbamoyl)-5-methylbenzoic acid (Preparation G, 26 mg, 0.037 mmol) in dichloromethane (1 mL) was added Hunig's base (15 mg, 0.114 mmol) to make a clear solution and HATU (18 mg, 0.05 mmol) was then added. After stirring for 20 min, the reaction mixture was added dipropylamine (6 mg, 0.057 mmol) and the reaction mixture was stirred at rt for 6 h. The crude mixture was purified by silica gel Flash Chromatography (0% to 10% to 30% EtOAc/Hexane step gradient) to give 27 mg of the title compound (90% yield): 1H NMR (CDCl3, 500 MHz) δ ppm 0.02 (3H, s), 0.06 (3H, s), 0.71 (3H, m), 0.85 (9H, s), 0.88 (3H, m), 0.96 (3H, m), 1.48-1.54 (12H, m), 1.67 (2H, m), 1.74 (2H, m), 2.03-2.09 (1H, m), 2.19 (1H, m), 2.38 (3H, s), 2.62 (1H, m), 2.94 (1H, m), 3.13 (2H, brd s), 3.26-3.36 (3H, m), 3.43 (2H, brd s), 3.76 (1H, m), 3.97 (1H, m), 4.04-4.07 (1H, m), 4.10-4.12 (1H, m), 4.58 (1H, m), 6.59 (1H, m), 6.76 (2H, d, J=5 Hz), 7.25 (1H, s), 7.60 (1H, s), 7.70 (1H, s), 7.98 (1H, brd s). MS (ESI) (M+H)+ 774.63.

المصدر