1-Hydroxybenzotriazole → HCID 69006888, compound

HRID 2102300Notes

Reaction equation

HRID 2102300 reaction equation
[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][C:10](=[O:14])[CH:9]1[CH2:15]C(O)=O)=[O:7])([CH3:4])([CH3:3])[CH3:2].[Cl:19][C:20]1[CH:21]=[C:22]([CH:27]=[CH:28][CH:29]=1)[C:23]([NH:25][OH:26])=[NH:24].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>CN(C=O)C.C(OCC)(=O)C>[C:1]([O:5][C:6]([N:8]1[CH2:13][CH2:12][NH:11][C:10](=[O:14])[CH:9]1[C:15]1[O:26][N:25]=[C:23]([C:22]2[CH:27]=[CH:28][CH:29]=[C:20]([Cl:19])[CH:21]=2)[N:24]=1)=[O:7])([CH3:2])([CH3:3])[CH3:4]

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 27560512-CARBOXYMETHYL-3-OXO-PIPERAZINE-1-CARBOXYLIC ACID TERT-BUTYL ESTERHCID 178513296HCID 178513296, compound

Product 1

HCID 69006888HCID 69006888, compoundYield 53.9%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
135 °C

Procedure

2-Carboxymethyl-3-oxo-piperazine-1-carboxylic acid tert-butyl ester (1.87 g, 7.25 mmol), 3-chloro-N-hydroxy-benzamidine (1.36 g, 7.98 mmol), HOBt (1.08 g, 7.98 mmol) and EDCl (1.53 g, 7.98 mmol) in DMF (20 mL) were stirred at room temperature overnight. The reaction mixture was diluted with ethyl acetate, washed with water (3 times), saturated sodium bicarbonate (2 times) and brine, dried over anhydrous sodium sulfate, filtered and concentrated. The residue was dissolved in DMF (20 mL) and then heated at 135° C. for 4 hours. After cooling, the reaction mixture was diluted with ethyl acetate, washed with water (3 times) and brine, dried over anhydrous sodium sulfate, filtered and concentrated. Purification was performed by flash chromatography on silica gel using hexanes:dichloromethane (1:1) to afford the titled compound (1.48 g, 52%, white foam solid). 1H NMR (CDCl3) δ (ppm): 8.08 (m, 1H), 7.97 (m, 1H), 7.46 (m, 2H), 6.35 (m, 1H), 5.04 (m, 1H), 4.31 (m, 1H), 3.68 (m,1H), 3.50 ( m, 2H), 3.27 (m, 2H), 1.35 (bs, 9H).

Workup

  1. washwashed with water (3 times), saturated sodium bicarbonate (2 times) and brine
  2. dry with materialdried over anhydrous sodium sulfate
  3. filtrationfiltered
  4. concentrationconcentrated
  5. dissolutionThe residue was dissolved in DMF (20 mL)
  6. temperatureAfter cooling
  7. additionthe reaction mixture was diluted with ethyl acetate
  8. washwashed with water (3 times) and brine
  9. dry with materialdried over anhydrous sodium sulfate
  10. filtrationfiltered
  11. concentrationconcentrated
  12. customPurification

Sources & evidence

ORD record
ord-888477187112469191994bf825daba66
Source dataset
uspto-grants-2009_08
Patent number
US07576077B2

Reaction notes

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