تفاعل #75963

معادلة التفاعل

4-((2R)-2-{[[(2S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-3-(phenyloxy)propyl](phenylmethyl)amino]methyl}-3,4-dihydro-2H-chromen-6-yl)-2-pyridinecarboxylic acid

4-fluorobenzylamine

1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride

1-hydroxybenzotriazole

→

title compound

4-((2R)-2-{[[(2S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-3-(phenyloxy)propyl](phenylmethyl)amino]methyl}-3,4-dihydro-2H-chromen-6-yl)-N-[(4-fluorophenyl)methyl]-2-pyridinecarboxamide

المذيبات

dichloromethane

ظروف التفاعل

المعالجة

1. 1
   تركيزbefore being concentrated in vacuo
2. 2
   أخرىto remove volatile components
3. 3
   أخرىThe crude residue was purified by flash chromatography on silica gel
4. 4
   غسيلeluted with 75:25 hexanes/ethyl acetate

الإجراء التجريبي

Into a solution of 4-((2R)-2-{[[(2S)-2-{[(1,1-dimethylethyl)(dimethyl)silyl]oxy}-3-(phenyloxy)propyl](phenylmethyl)amino]methyl}-3,4-dihydro-2H-chromen-6-yl)-2-pyridinecarboxylic acid (Example 90, 82 mg, 0.13 mmol) in dichloromethane (2 mL) was added 4-fluorobenzylamine (33 mg, 0.26 mmol, 2.0 eq.), 1-[3-(dimethylamino)propyl]-3-ethylcarbodiimide hydrochloride (50 mg, 0.26 mmol, 2.0 eq.), and 1-hydroxybenzotriazole (35 mg, 0.26 mmol, 2.0 eq.). The solution was stirred overnight at room temperature before being concentrated in vacuo to remove volatile components. The crude residue was purified by flash chromatography on silica gel eluted with 75:25 hexanes/ethyl acetate. The title compound was obtained as a yellow oil (34 mg, 35%): 1H NMR (300 MHz, CDCl3) δ8.47 (d, 1 H), 8.40 (s, 2 H), 7.55 (dd, 1 H), 7.44-7.39 (m, 2 H), 7.34-7.29 (m, 4 H), 7.25-7.20 (m, 4 H), 7.01 (t, 2 H), 6.93-6.80 (m, 4 H), 4.64 (d, 2 H), 4.22-4.16 (m, 1 H), 4.11-4.05 (m, 1 H), 3.83 (s, 2 H), 3.75 (dd, 1 H), 2.94-2.80 (m, 2 H), 2.73-2.67 (m, 4 H), 1.71-1.57 (m, 2 H), 0.86 (s, 9H), 0.09 (s, 3 H), 0.05 (s, 3 H); MS m/z 746.5 (M+).

المصدر