Dimethylformamide → Ethyl 2-(2-biphenylylmethyl)-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinecarboxylate

HRID 2046278Notes

Reaction equation

HRID 2046278 reaction equation
[C:1]1([C:24]2[CH:29]=[CH:28][CH:27]=[CH:26][CH:25]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][N:8]1[C:13](=[O:14])[C:12]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:11]([OH:20])[C:10]([CH:21]([CH3:23])[CH3:22])=[N:9]1.OC1C(C(C)C)=NNC(=O)[C:32]=1[C:41]([O:43]CC)=[O:42].[H-].[Na+].C1(C2C=CC=CC=2CBr)C=CC=CC=1.C[N:63](C)C=O>>[C:1]1([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][N:8]1[C:13](=[O:14])[C:12]([C:15]([NH:63][CH2:32][C:41]([OH:43])=[O:42])=[O:16])=[C:11]([OH:20])[C:10]([CH:21]([CH3:23])[CH3:22])=[N:9]1.[C:1]1([C:24]2[CH:25]=[CH:26][CH:27]=[CH:28][CH:29]=2)[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[CH2:7][N:8]1[C:13](=[O:14])[C:12]([C:15]([O:17][CH2:18][CH3:19])=[O:16])=[C:11]([OH:20])[C:10]([CH:21]([CH3:22])[CH3:23])=[N:9]1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 2633651-(Bromomethyl)-2-phenylbenzeneHCID 68813243Ethyl 2-(2-biphenylylmethyl)-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinecarboxylateHCID 68815345Ethyl 5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinecarboxylate

Product 2

HCID 54739219N-{[2-(2-Biphenylylmethyl)-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinyl]carbonyl}glycineHCID 68813243Ethyl 2-(2-biphenylylmethyl)-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinecarboxylateYield 58%

Procedure

Ethyl 2-(2-biphenylylmethyl)-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinecarboxylate. To a solution of ethyl 5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinecarboxylate (example 46(a), 125 mg, 0.55 mmol) in N,N-Dimethylformamide (DMF) (5 ml) at 0° C. was added sodium hydride (55 mg, 0.138 mmol) in portions. The reaction mixture was stirred at room temperature for 45 minutes and then cooled back to 0° C. and 2-phenylbenzyl bromide (101 μl, 0.55 mmol) was added. The mixture was stirred at ambient temperature for 3 hours then quenched with 1N HCl (3 ml) extracted with ethyl acetate (2×20 ml). The organic layers were combined, dried over Magnesium sulfate, filtered and solvents removed with rotary evaporation. The crude oil was purified by flash column chromatography (10-100% ethyl acetate in hexanes) to provide the title compound ethyl 2-(2-biphenylylmethyl)-5-hydroxy-6-(1-methylethyl)-3-oxo-2,3-dihydro-4-pyridazinecarboxylate (126 mg, 0.32 mmol, 58% yield) as a pale yellow oil that was used immediately in the next step. MS (ES+) m/e 393 [M+H]+.

Workup

  1. temperaturecooled back to 0° C.
  2. stirringThe mixture was stirred at ambient temperature for 3 hours
  3. customthen quenched with 1N HCl (3 ml)
  4. extractionextracted with ethyl acetate (2×20 ml)
  5. dry with materialdried over Magnesium sulfate
  6. filtrationfiltered
  7. customsolvents removed with rotary evaporation
  8. customThe crude oil was purified by flash column chromatography (10-100% ethyl acetate in hexanes)

Sources & evidence

ORD record
ord-a29373af92794b3b94e4474bd6443108
Source dataset
uspto-grants-2013_11
Patent number
USRE044613E1

Reaction notes

Loading…