反応 #2335

反応方程式

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

HOBt

HBTU

diisopropylethylamine

DMF

→

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

溶媒

H2O

反応条件

後処理

1. 1
   その他The 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
   その他The organic layer was separated
6. 6
   抽出the aqueous layer was re-extracted with dichloromethane (30 ml)
7. 7
   洗浄The combined organic extracts were washed with water, saturated sodium bicarbonate solution, water
8. 8
   乾燥dried (MgSO4)
9. 9
   その他evaporated
10. 10
    ろ過The residue was purified by filtration through a short bed of activated (grade II) alumina by elution with ethyl acetate/methanol, 5:1

実験手順

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)+.

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