Methanol → HCID 59716562, compound

HRID 2224290Notes

Reaction equation

HRID 2224290 reaction equation
[F:1][C:2]([F:35])([F:34])[C:3]1[CH:33]=[CH:32][C:6]([CH2:7][N:8]2[C:30](=[O:31])[N:11]3[N:12]=[CH:13][C:14]([C:23]4[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=4)=[C:15]([C:16]4[CH:21]=[CH:20][C:19]([Cl:22])=[CH:18][CH:17]=4)[C:10]3=[N:9]2)=[CH:5][CH:4]=1.[CH3:36][Mg]Br.CO>C1COCC1>[F:35][C:2]([F:1])([F:34])[C:3]1[CH:33]=[CH:32][C:6]([CH2:7][N:8]2[C:30](=[O:31])[N:11]3[NH:12][CH:13]([CH3:36])[C:14]([C:23]4[CH:28]=[CH:27][C:26]([Cl:29])=[CH:25][CH:24]=4)=[C:15]([C:16]4[CH:17]=[CH:18][C:19]([Cl:22])=[CH:20][CH:21]=4)[C:10]3=[N:9]2)=[CH:5][CH:4]=1

Participants

5

Reactant 3

HCID 887MethanolHCID 11988491HCID 11988491, compoundHCID 178418573HCID 178418573, compound

Product 1

HCID 59716562HCID 59716562, compoundYield 98.6%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Conditions

Temperature
-20 °C

Procedure

To a solution of 2-(4-(trifluoromethyl)benzyl)-7,8-bis(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one, (250 mg, 0.485 mmol), prepared as described in Example 17, in THF (4 mL) at −20° C. was added methyl magnesium bromide (0.81 mL, 2.43 mmol, 3.0 M in Et2O). The reaction was stirred at −20° C. for 30 min. LC-MS showed that the reaction was complete. To the reaction mixture was added 20 mL of MeOH to quench the reaction. The reaction was allowed to warm to RT and the solvent was evaporated. The residue was diluted with EtOAc (100 mL), washed with H2O (10 mL) and saturated aqueous NaCl (5 mL×2). The organic layer was dried (MgSO4), filtered and concentrated under reduced pressure. The crude product was purified by silica gel column chromatography using an automated system, eluting with a gradient of (0% to 80% EtOAc for 40 min. and holds at 80% for 10 min.) to give the title compound, 2-(4-(Trifluoromethyl)benzyl)-7,8-bis(4-chlorophenyl)-6-methyl-5,6-dihydro-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (254 mg), as a beige solid in 98% yield. HPLC retention time: 4.23 min; MS [M+H]+: found 531. 1HNMR (CDCl3, 400 MHz) 67.52 (d, 2H), 7.38 (d, 2H), 7.17-7.11 (m, 4H), 7.05 (dd, 2H), 6.94 (dd, 2H), 4.94 (s, 2H), 4.16 (q, 1H), 1.24 (d, 3H).

Workup

  1. customto quench
  2. customthe reaction
  3. temperatureto warm to RT
  4. customthe solvent was evaporated
  5. additionThe residue was diluted with EtOAc (100 mL)
  6. washwashed with H2O (10 mL) and saturated aqueous NaCl (5 mL×2)
  7. dry with materialThe organic layer was dried (MgSO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe crude product was purified by silica gel column chromatography
  11. washeluting with a gradient of (0% to 80% EtOAc for 40 min. and holds at 80% for 10 min.)

Sources & evidence

ORD record
ord-0f71e0d77c3b4d0fbf7a534e176c4bb6
Source dataset
uspto-grants-2008_05
Patent number
US07378418B2

Reaction notes

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