2,2,2-Trifluoroethanol → 6-(2-Chlorophenyl)-7-(4-chlorophenyl)-3-(2,2,2-trifluoroethoxy)-[1,2,4]triazolo[4,3-b]pyridazine

HRID 1867874Notes

Reaction equation

HRID 1867874 reaction equation
Cl[C:2]1[N:6]2[N:7]=[C:8]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][C:19]=3[Cl:24])[C:9]([C:11]3[CH:16]=[CH:15][C:14]([Cl:17])=[CH:13][CH:12]=3)=[CH:10][C:5]2=[N:4][N:3]=1.[F:25][C:26]([F:30])([F:29])[CH2:27][OH:28].C(N=P1(N(CC)CC)N(C)CCCN1C)(C)(C)C>C1COCC1>[Cl:24][C:19]1[CH:20]=[CH:21][CH:22]=[CH:23][C:18]=1[C:8]1[C:9]([C:11]2[CH:12]=[CH:13][C:14]([Cl:17])=[CH:15][CH:16]=2)=[CH:10][C:5]2[N:6]([C:2]([O:28][CH2:27][C:26]([F:30])([F:29])[F:25])=[N:3][N:4]=2)[N:7]=1

Participants

5

Reactant 3

HCID 64092,2,2-TrifluoroethanolHCID 35138512-((1,1-Dimethylethyl)imino)-N,N-diethylhexahydro-1,3-dimethyl-2lambda5-1,3,2-diazaphosphorin-2-amineHCID 579797573-Chloro-6-(2-chlorophenyl)-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazine

Product 1

HCID 119931076-(2-Chlorophenyl)-7-(4-chlorophenyl)-3-(2,2,2-trifluoroethoxy)-[1,2,4]triazolo[4,3-b]pyridazineYield 68.3%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent

Procedure

A mixture 3-chloro-6-(2-chlorophenyl)-7-(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazine (38 mg, 0.1 mmol), 2,2,2-trifluoroethanol (22 μL, 0.2 mmol), 2-tert-butylimino-2-diethylamino-1,3-dimethyl-perhydro-1,3,2-diazaphosphorine (60 μL, 0.3 mmol) and anhydrous THF (0.5 mL) in a sealed tube was stirred at 70° C. for 3 days. After cooling to room temperature, the reaction mixture was concentrated under reduced pressure. The obtained residue was purified using reverse phase preparative HPLC (Conditions: Phenomenex Luna 5μ C18 21.2×100 mm; Eluted with 60% to 100% B, 10 min gradient, 100% B hold for 5 min, (A=90% H2O, 10% MeOH and B=10% H2O, 90% MeOH); Flow rate at 20 mL/min, UV detection at 220 nm) to yield 30 mg of the desired product with 90% purity. The impure product was further purified using a silica gel cartridge (4 g) eluting with a gradient of EtOAc (30-100%) in hexanes to afford 24 mg (55%) of the title compound as a white solid. HPLC/MS (method A): retention time=3.81 min, (M+H)+=439.1. 1H NMR (CDCl3, 400 MHz): δ 7.92 (s, 1H), 7.40-7.49 (m, 1H), 7.29-7.33 (m, 2H), 7.14-7.30 (m, 3H), 7.09 (d, J=8.56 Hz, 2H), 5.05-5.07 (m, 2H).

Workup

  1. concentrationthe reaction mixture was concentrated under reduced pressure
  2. customThe obtained residue was purified
  3. washEluted with 60% to 100% B, 10 min gradient, 100% B hold for 5 min

Sources & evidence

ORD record
ord-bf70253dd5124cb1a074762b1401c396
Source dataset
uspto-grants-2009_12
Patent number
US07632837B2

Reaction notes

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