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

HRID 864847

Reaktionsgleichung

Reaktionsgleichung von HRID 864847
[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

Komponenten

7

Edukt 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

Produkt 1

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

Reagenzien, Katalysatoren, Lösungsmittel 1

HCID 962WaterLösungsmittel

Versuchsvorschrift

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) δ1.18 (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)+.

Aufarbeitung

  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

Quellen und Nachweise

ORD-Eintrag
ord-f4003541246b472d8464728cff468a67
Quelldatensatz
uspto-grants-1996_10
Patentnummer
US05563141

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