Methanol → 6-benzyl-7,8-bis(4-chlorophenyl)-2-methyl-5,6-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one

HRID 2224295Notes

Reaction equation

HRID 2224295 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[N:12][N:11]3[C:14](=[O:18])[N:15]([CH3:17])[N:16]=[C:10]3[C:9]=2[C:19]2[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=2)=[CH:4][CH:3]=1.[CH2:26]([Mg]Br)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1.CO>C1COCC1>[CH2:26]([CH:13]1[NH:12][N:11]2[C:14](=[O:18])[N:15]([CH3:17])[N:16]=[C:10]2[C:9]([C:19]2[CH:20]=[CH:21][C:22]([Cl:25])=[CH:23][CH:24]=2)=[C:8]1[C:5]1[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=1)[C:27]1[CH:32]=[CH:31][CH:30]=[CH:29][CH:28]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 59716854HCID 59716854, compoundHCID 178419663HCID 178419663, compound

Product 1

HCID 597166716-benzyl-7,8-bis(4-chlorophenyl)-2-methyl-5,6-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-oneYield 46.4%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of 7,8-bis(4-chlorophenyl)-2-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (50 mg, 0.135 mmol), prepared as described in Example 474, in THF (1 mL) at −20° C. was added benzyl magnesium bromide (0.34 mL, 0.675 mmol, 2.0 M in THF). The reaction was stirred at −20° C. for 30 min. After this time MeOH (5 mL) was added to quench the reaction. The reaction was allowed to warm to RT and the reaction mixture was concentrated under reduced pressure. The residue was purified by silica gel column chromatography using an automated system eluting with a gradient of (0% to 80% EtOAc for 20 min. and holds at 80% for 20 min.) to give the title compound, 6-benzyl-7,8-bis(4-chlorophenyl)-2-methyl-5,6-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (29 mg, 46%) as a beige solid. HPLC retention time: 4.10 min; MS [M+H]+: found 463. 1H NMR (CDCl3, 400 MHz) δ 7.30-6.90 (m, 13H), 4.22 (t, 1H), 3.36 (s, 3H), 2.90-2.75 (m, 2H).

Workup

  1. customto quench
  2. customthe reaction
  3. temperatureto warm to RT
  4. concentrationthe reaction mixture was concentrated under reduced pressure
  5. customThe residue was purified by silica gel column chromatography
  6. washeluting with a gradient of (0% to 80% EtOAc for 20 min. and holds at 80% for 20 min.)

Sources & evidence

ORD record
ord-fb1b737df3a54ae58b7f2ae392fea018
Source dataset
uspto-grants-2008_05
Patent number
US07378418B2

Reaction notes

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