Phenol → HCID 86599006, compound

HRID 2224256Notes

Reaction equation

HRID 2224256 reaction equation
[F:1][C:2]([F:29])([F:28])[C:3]1[CH:27]=[CH:26][C:6]([CH2:7][N:8]2[C:24](=[O:25])[N:11]3[N:12]=[CH:13][C:14](Cl)=[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.[C:30]1([OH:36])[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=1.C([O-])([O-])=O.[K+].[K+]>CN(C=O)C.[OH-].[Na+]>[F:1][C:2]([F:28])([F:29])[C:3]1[CH:4]=[CH:5][C:6]([CH2:7][N:8]2[C:24](=[O:25])[N:11]3[N:12]=[CH:13][C:14]([O:36][C:30]4[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=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:26][CH:27]=1.[Cl:22][C:19]1[CH:18]=[CH:17][C:16]([C:15]2[C:10]3[N:11]([C:24](=[O:25])[NH:8][N:9]=3)[N:12]=[CH:13][C:14]=2[O:36][C:30]2[CH:35]=[CH:34][CH:33]=[CH:32][CH:31]=2)=[CH:21][CH:20]=1

Participants

7

Reactant 3

HCID 996PhenolHCID 11430Potassium CarbonateHCID 59716779HCID 59716779, compound

Product 2

HCID 59716751HCID 59716751, compoundHCID 86599006HCID 86599006, compoundYield 181.7%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 14798Sodium HydroxideSolvent

Procedure

To a solution of 2-(4-(trifluoromethyl)benzyl)-8-(4-chlorophenyl)-7-chloro-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (17 mg, 0.039 mmol), prepared as described in Example 274 in DMF (0.5 mL) was added phenol (7.2 mg, 0.077 mmol), followed by K2CO3 (11 mg, 0.077 mmol). The reaction mixture was stirred at RT for 16 h, and then diluted with 1M aqueous NaOH (3 mL). A yellow precipitate was formed. The solid was collected by filtration and washed thoroughly with H2O. The crude product was purified by reverse phase HPLC to give the title compound, 2-(4-trifluoromethyl)benzyl)-8-(4-chlorophenyl)-7-phenoxy-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (12 mg, 62%) as a yellow solid. HPLC: 99% at 8.31 min (retention time) (Conditions: Zorbax SB C18 (4.6×75 mm); Eluted with 0% to 100% B, 8 min gradient. (A=90% H2O—10% MeOH—0.1% H3PO4 and B=10% H2O—90% MeOH—0.1% H3PO4); Flow rate at 2.5 mL/min. UV detection at 220 nm). MS (ES): m/z 497 [M+H]+; 1H NMR (CDCl3, 400 MHz): δ 5.25 (s, 2H), 6.99 (d, J=8 Hz, 2H), 7.21 (t, J=8 Hz, 1H), 7.37-7.44 (m, 4H), 7.54 (d, J=8 Hz, 2H), 7.61 (d, J=8 Hz, 2H), 7.79-7.82 (m, 2H), 7.90 (s, 1H).

Workup

  1. customA yellow precipitate was formed
  2. filtrationThe solid was collected by filtration
  3. washwashed thoroughly with H2O
  4. customThe crude product was purified by reverse phase HPLC

Sources & evidence

ORD record
ord-df78e966b7ff4f958b5ede61e1946d86
Source dataset
uspto-grants-2008_05
Patent number
US07378418B2

Reaction notes

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