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

HRID 2046271Notes

Reaction equation

HRID 2046271 reaction equation
[OH:1][C:2]1[C:7]([CH:8]([CH3:10])[CH3:9])=[N:6][NH:5][C:4](=[O:11])[C:3]=1[C:12]([O:14]CC)=O.[H-].[Na+].[Br:19][C:20]1[CH:27]=[CH:26][C:23]([CH2:24]Br)=[CH:22][CH:21]=1.[Na+].[NH2:29][CH2:30][C:31]([O-:33])=[O:32].Cl>CN(C)C=O.O>[Br:19][C:20]1[CH:27]=[CH:26][C:23]([CH2:24][N:5]2[C:4](=[O:11])[C:3]([C:12]([NH:29][CH2:30][C:31]([OH:33])=[O:32])=[O:14])=[C:2]([OH:1])[C:7]([CH:8]([CH3:9])[CH3:10])=[N:6]2)=[CH:22][CH:21]=1

Participants

8

Reactant 5

HCID 313Hydrochloric AcidHCID 24758Sodium hydrideHCID 685274-Bromobenzyl bromideHCID 4684308Sodium GlycinateHCID 68815345Ethyl 5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinecarboxylate

Product 1

HCID 54739228N-{[2-[(4-Bromophenyl)methyl]-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycineYield 30.4%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of ethyl 5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinecarboxylate (example 46a, 1.32 g, 5.83 mmol) in N,N-Dimethylformamide (DMF) (30 ml) at 0° C. was added sodium hydride (0.5 g, 14.58 mmol) in portions. The reaction mixture was stirred at room temperature for 30 minutes and then cooled back to 0° C. and 4-bromobenzyl bromide (1.46 g, 5.83 mmol) was added. The mixture was stirred at ambient temperature for 2 hours then quenched with 1N HCl (10 ml). The aqueous solution was extracted with ethyl acetate (2×50 ml), the organic layers combined, dried over Magnesium sulfate, filtered and solvents removed with rotary evaporation. The crude residue was dissolved in 2-methoxyethanol (10 ml), place in a 20 ml microwave tube and glycine sodium salt (0.75 g, 7.7 mmol) was added. The mixture was irradiated at 150° C. for 20 minutes, diluted with water (15 ml) and acidified with 1N HCl to cause a precipitate. The precipitate was collected by filtration and dried to give the product as an off white solid (0.750 g, 1.77 mmol, 30.3%) 1H NMR (400 MHz, DMSO-d6) d ppm 15.89 (s, 1H), 12.97 (s, 1H), 10.16 (t, J=5.31 Hz, 1H), 7.55 (d, J=8.34 Hz, 2H), 7.26 (d, J=8.34 Hz, 2 H), 5.22 (s, 2H), 4.10 (d, J=5.81 Hz, 2H), 3.18 (m, 1H), 1.19 (d, J=6.82 Hz, 6H). MS (ES+) m/e 425 [M+H]+.

Workup

  1. temperaturecooled back to 0° C.
  2. stirringThe mixture was stirred at ambient temperature for 2 hours
  3. customthen quenched with 1N HCl (10 ml)
  4. extractionThe aqueous solution was extracted with ethyl acetate (2×50 ml)
  5. dry with materialdried over Magnesium sulfate
  6. filtrationfiltered
  7. customsolvents removed with rotary evaporation
  8. dissolutionThe crude residue was dissolved in 2-methoxyethanol (10 ml)
  9. customThe mixture was irradiated at 150° C. for 20 minutes
  10. filtrationThe precipitate was collected by filtration
  11. customdried

Sources & evidence

ORD record
ord-0a9c7b5345274e15ac9e2196e875347d
Source dataset
uspto-grants-2013_11
Patent number
USRE044613E1

Reaction notes

Loading…