تفاعل #49234

معادلة التفاعل

(1S,2S)-1-((2R,4R)-4-(allyloxy)-1-benzhydrylpyrrolidin-2-yl)-2-amino-3-(3,5-difluorophenyl)propan-1-ol

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

( A )

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

N1-((1S,2S)-1-((2R,4R)-4-(allyloxy)-1-benzhydrylpyrrolidin-2-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-N3,N3-dipropylisophthalamide

3-(dipropylcarbamoyl)benzoic acid

Hunig's base

HATU

→

title compound

المردود 89.0%

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

المردود 89.0%

المذيبات

dichloromethane

ظروف التفاعل

المعالجة

1. 1
   workup.STIRRINGthe reaction mixture was stirred at rt overnight
2. 2
   أخرىThe crude mixture was purified by silica gel Flash Chromatography (0% to 20% to 40% to 50% EtOAc/Hexane step gradient)

الإجراء التجريبي

Step 4 (A): N1-((1S,2S)-1-((2R,4R)-4-(allyloxy)-1-benzhydrylpyrrolidin-2-yl)-3-(3,5-difluorophenyl)-1-hydroxypropan-2-yl)-N3,N3-dipropylisophthalamide. To a solution of 3-(dipropylcarbamoyl)benzoic acid (31 mg, 0.12 mmol) in dichloromethane (3 mL) were added Hunig's base (43 mg, 0.33 mmol) and HATU (54 mg, 0.143 mmol). After stirring for 20 min, the reaction mixture was added (1S,2S)-1-((2R,4R)-4-(allyloxy)-1-benzhydrylpyrrolidin-2-yl)-2-amino-3-(3,5-difluorophenyl)propan-1-ol (Preparation (C), 54 mg, 0.11 mmol) and the reaction mixture was stirred at rt overnight. The crude mixture was purified by silica gel Flash Chromatography (0% to 20% to 40% to 50% EtOAc/Hexane step gradient) to give 70 mg of the title compound (89% yield): 1H NMR (CDCl3, 500 MHz) δ 0.74 (3H, brd s), 1.00 (3H, brd s), 1.53 (2H, brd s), 1.73 (2H, brd s), 2.02-2.09 (1H, m), 2.17 (1H, d, J=10 Hz), 2.26 (1H, dd, J=5, 10 Hz), 2.68 (1H, d, J=10 Hz), 2.84 (1H, dd, J=5, 15 Hz), 2.96 (1H, dd, J=5, 15 Hz), 3.09 (1H, d, J=10 Hz), 3.16 (2H, brd s), 3.25 (1H, d, J=10 Hz), 3.49 (2H, brd s), 3.91-3.93 (2H, m), 3.96-4.11 (3H, m), 4.50 (1H, s), 4.91 (1H, d, J=10 Hz), 5.22 (1H, dd, J=5, 10 Hz), 5.31 (1H, m), 5.90-5.98 (1H, m), 6.64-6.69 (3H, m), 6.91-6.97 (3H, m), 7.15-7.20 (3H, m), 7.22-7.25 (2H, m), 7.34 (2H, d, J=5 Hz), 7.47-7.57 (4H, m). MS (ESI) (M+H)+ 710.37.

المصدر