Hydrochloric Acid → N-({5-Hydroxy-6-(1-methylethyl)-2-[(2-nitrophenyl)methyl]-3-oxo-2,3-dihydro-4-pyridazinyl}carbonyl)glycine

HRID 1822386Notes

Reaction equation

HRID 1822386 reaction equation
[OH:1][C:2]1[C:7]([CH:8]([CH3:10])[CH3:9])=[N:6][N:5]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N+:18]([O-:20])=[O:19])[C:4](=[O:21])[C:3]=1[C:22](OCC)=[O:23].[H-].[Na+].[N+:29](C1C=CC=CC=1CBr)([O-])=O.Cl.CC[O:43][C:44]([CH3:46])=[O:45]>CN(C)C=O.O>[OH:1][C:2]1[C:7]([CH:8]([CH3:9])[CH3:10])=[N:6][N:5]([CH2:11][C:12]2[CH:17]=[CH:16][CH:15]=[CH:14][C:13]=2[N+:18]([O-:20])=[O:19])[C:4](=[O:21])[C:3]=1[C:22]([NH:29][CH2:46][C:44]([OH:43])=[O:45])=[O:23]

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 8857Ethyl AcetateHCID 24758Sodium hydrideHCID 77569alpha-Bromo-2-nitrotolueneHCID 68812174HCID 68812174, compound

Product 1

HCID 54747358N-({5-Hydroxy-6-(1-methylethyl)-2-[(2-nitrophenyl)methyl]-3-oxo-2,3-dihydro-4-pyridazinyl}carbonyl)glycineYield 65%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

Ethyl 5-hydroxy-6-(1-methylethyl)-2-[(2-nitrophenyl)methyl]-3-oxo-2,3-dihydro-4-pyridazinecarboxylate. Sodium hydride (88 mg, 2.21 mmol) was added to a solution of the compound from example 14a) (200 mg, 0.88 mmol) in N,N-Dimethylformamide (DMF) (3.5 mL) at 0° C. The reaction was brought to room temperature and stirred for 30 minutes. The temperature was then reduced to 0° C. and 2-nitrobenzyl bromide (191 mg, 0.88 mmol) was added. The reaction was brought to room temperature and stirred for 3 h followed by the addition of 1N HCl. The solution was diluted with EtOAc and H2O and the layers separated. The aqueous layer was backextracted with EtOAc several times. The combined organic layers were washed with Brine, dried (MgSO4), filtered and concentrated. The product was purified by column chromatography (SiO2, 30-60% EtOAc/Hexanes) to give the title compound (206 mg, 65%). 1H NMR (400 MHz, DMSO-d6) δ ppm 12.37 (s, 1H) 8.07 (dd, J=8.21, 1.14 Hz, 1H) 7.72 (td, J=7.58, 1.26 Hz, 1H) 7.54-7.62 (m, 1H) 7.29 (dd, J=7.71, 1.14 Hz, 1H) 5.46 (s, 2H) 4.27 (q, J=7.07 Hz, 2H) 3.13 (sept, J=6.78 Hz, 1H) 1.25 (t, J=7.20 Hz, 3H) 1.09 (d, J=6.82 Hz, 6H).

Workup

  1. customwas brought to room temperature
  2. customwas then reduced to 0° C.
  3. customwas brought to room temperature
  4. stirringstirred for 3 h
  5. customthe layers separated
  6. washThe combined organic layers were washed with Brine
  7. dry with materialdried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe product was purified by column chromatography (SiO2, 30-60% EtOAc/Hexanes)

Sources & evidence

ORD record
ord-c22c27fc29e6407190bc242c1c2e9f89
Source dataset
uspto-grants-2009_10
Patent number
US07608621B2

Reaction notes

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