Reaction #2335

Reaction equation

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

HOBt

HBTU

diisopropylethylamine

DMF

→

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

Solvents

H2O

Conditions

Workup

1. 1
   OtherThe 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
   OtherThe organic layer was separated
6. 6
   Extractionthe aqueous layer was re-extracted with dichloromethane (30 ml)
7. 7
   WashThe combined organic extracts were washed with water, saturated sodium bicarbonate solution, water
8. 8
   Dryingdried (MgSO4)
9. 9
   Otherevaporated
10. 10
    FiltrationThe residue was purified by filtration through a short bed of activated (grade II) alumina by elution with ethyl acetate/methanol, 5:1

Procedure

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)+.

Source