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

HRID 1291888

Reaction equation

HRID 1291888 reaction equation
[N:1]1[CH:6]=[CH:5][C:4]([CH:7]2[CH2:12][NH:11][CH2:10][CH2:9][N:8]2[C:13]2[CH:21]=[CH:20][C:16](C(O)=O)=[CH:15][CH:14]=2)=[CH:3][CH:2]=1.C1C=CC2N([OH:31])N=NC=2C=1.CN([C:35]([O:39]N1N=NC2C=CC=CC1=2)=[N+:36]([CH3:38])[CH3:37])C.F[P-](F)(F)(F)(F)F.C(N([CH:62]([CH3:64])C)CC)(C)C.CN([CH:68]=[O:69])C>O>[N:1]1[CH:2]=[CH:3][C:4]([CH:7]2[CH2:12][NH:11][CH2:10][CH2:9][N:8]2[C:13]2[CH:21]=[CH:20][C:16]([C:35]([N:36]([CH3:37])[CH2:38][C:68]([O:69][CH2:62][CH3:64])=[O:31])=[O:39])=[CH:15][CH:14]=2)=[CH:5][CH:6]=1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 757711-HydroxybenzotriazoleHCID 81531DiisopropylethylamineHCID 2733084Methanaminium, N-((1H-benzotriazol-1-yloxy)(dimethylamino)methylene)-N-methyl-, hexafluorophosphate(1-) (1:1)HCID 189183004-((4-Pyridyl)piperazin-1-yl)benzoic acid

Product 1

HCID 18918248ethyl N-(4-[(4-pyridyl)piperazin-1-yl]benzoyl)-N-methylglycinate

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

To a stirred mixture of 4-[(4-pyridyl)piperazin-1-yl]benzoic acid (prepared as in Example 56(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)+.

Workup

  1. customThe ice-bath was removed
  2. additionwas added
  3. stirringThe reaction mixture was stirred at room temperature under argon overnight
  4. additionthen diluted with dichloromethane (30 ml) and water (30 ml)
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was re-extracted with dichloromethane (30 ml)
  7. washThe combined organic extracts were washed with water, saturated sodium bicarbonate solution, water
  8. dry with materialdried (MgSO4)
  9. customevaporated
  10. filtrationThe residue was purified by filtration through a short bed of activated (grade II) alumina by elution with ethyl acetate/methanol, 5:1

Sources & evidence

ORD record
ord-92e044bf43de40678c94c751a0a7b616
Source dataset
uspto-grants-1998_05
Patent number
US05753659

Linked notes

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