반응 #2335

반응 방정식

4-[(4-pyridyl)piperazin-1-yl]benzoic acid

HOBt

HBTU

diisopropylethylamine

DMF

→

ethyl N-(4-[(4-pyridyl)piperazin-1-yl]benzoyl)-N-methylglycinate

용매

H2O

반응 조건

후처리

1. 1
   기타The ice-bath was removed
2. 2
   workup.ADDITIONwas added
3. 3
   workup.STIRRINGThe reaction mixture was stirred at room temperature under argon overnight
4. 4
   workup.ADDITIONthen diluted with dichloromethane (30 ml) and water (30 ml)
5. 5
   기타The organic layer was separated
6. 6
   추출the aqueous layer was re-extracted with dichloromethane (30 ml)
7. 7
   세척The combined organic extracts were washed with water, saturated sodium bicarbonate solution, water
8. 8
   건조dried (MgSO4)
9. 9
   기타evaporated
10. 10
    여과The residue was purified by filtration through a short bed of activated (grade II) alumina by elution with ethyl acetate/methanol, 5:1

실험 절차

To a stirred mixture of 4-[(4-pyridyl)piperazin-1-yl]benzoic acid (prepared as in Example 30(i)) (311 mg), HOBt.H2O (170 mg) and HBTU (416 mg) in DMF (5 ml) at 0°-5° C. under argon was added diisopropylethylamine (0.75 ml). The ice-bath was removed and the reaction mixture was stirred at room temperature for 15 minutes before solid sarcosine, ethyl ester hydrochloride (154 mg) was added. The reaction mixture was stirred at room temperature under argon overnight then diluted with dichloromethane (30 ml) and water (30 ml). The organic layer was separated and the aqueous layer was re-extracted with dichloromethane (30 ml). The combined organic extracts were washed with water, saturated sodium bicarbonate solution, water, dried (MgSO4) and evaporated. The residue was purified by filtration through a short bed of activated (grade II) alumina by elution with ethyl acetate/methanol, 5:1, to give ethyl N-(4-[(4-pyridyl)piperazin-1-yl]benzoyl)-N-methylglycinate (92 mg) as an amorphous solid: NMR (d6 -DMSO+CD3CO2D) δ 1.18 (3H, t), 2.98 (3H, s), 3.44 (4H, m), 3.79 (4H, m), 4.11 (4H, m), 6.94 (2H, d), 7.12 (2H, d), 7.31 (2H, br, d), 8.19 (2H, d); m/Z 383 (M+H)+.

출처