Toluene → 7,8-bis(4-chlorophenyl)-2-((5-(trifluoromethyl)pyridin-2-yl)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one

HRID 2224203Notes

Reaction equation

HRID 2224203 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:17])[NH:15][N:16]=[C:10]3[C:9]=2[C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=[CH:4][CH:3]=1.C1C=CC(P(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[F:44][C:45]([F:55])([F:54])[C:46]1[CH:47]=[CH:48][C:49]([CH2:52]O)=[N:50][CH:51]=1.N(C(OCC)=O)=NC(OCC)=O.C1(C)C=CC=CC=1>C1COCC1.O>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[CH:13]=[N:12][N:11]3[C:14](=[O:17])[N:15]([CH2:52][C:49]4[CH:48]=[CH:47][C:46]([C:45]([F:54])([F:44])[F:55])=[CH:51][N:50]=4)[N:16]=[C:10]3[C:9]=2[C:18]2[CH:23]=[CH:22][C:21]([Cl:24])=[CH:20][CH:19]=2)=[CH:4][CH:3]=1

Participants

8

Reactant 5

HCID 1140TolueneHCID 11776TriphenylphosphineHCID 220568ethyl N-ethoxycarbonyliminocarbamateHCID 3820787(5-(Trifluoromethyl)pyridin-2-yl)methanolHCID 111641617,8-bis(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one

Product 1

HCID 119890137,8-bis(4-chlorophenyl)-2-((5-(trifluoromethyl)pyridin-2-yl)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-oneYield 48%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent

Procedure

To a solution of 7,8-bis(4-chlorophenyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (100 mg, 0.28 mmol), prepared as described in Example 1, Ph3P (220 mg, 0.84 mmol) and (5-trifluoromethyl-pyridin-2-yl)methanol (50 mg, 0.28 mmol) in THF (2.0 mL) was added 40 wt % diethyl azodicarboxylate (DEAD) solution in toluene (0.33 mL, 0.84 mmol) at RT under argon. The reaction was stirred at RT for 30 min. Water (5.0 mL) was then added and the resulting mixture was extracted with EtOAc (3×5 mL). The combined organic layers were washed with water (2×5 mL) followed by saturated aqueous NaCl (2×5 mL). The combined organic layers were concentrated under reduced pressure to obtain the crude product. This crude product was purified using reverse phase preparative HPLC to give the title compound 7,8-bis(4-chlorophenyl)-2-((5-(trifluoromethyl)pyridin-2-yl)methyl)-[1,2,4]triazolo[4,3-b]pyridazin-3(2H)-one (69.2 mg, 48%) as a yellow solid. MS (M+H)=516; 1H NMR (CDCl3): δ 8.83 (1H, s), 8.20 (1H, s), 7.93 (1H, d, J=8.2 Hz), 7.40 (1H, d, J=10.0 Hz), 7.26-7.34 (6H, m), 7.11 (2H, d, J=10.0 Hz), 5.47 (2H, s).

Workup

  1. extractionthe resulting mixture was extracted with EtOAc (3×5 mL)
  2. washThe combined organic layers were washed with water (2×5 mL)
  3. concentrationThe combined organic layers were concentrated under reduced pressure
  4. customto obtain the crude product
  5. customThis crude product was purified

Sources & evidence

ORD record
ord-959104987e294ffd9d2919f622a60d75
Source dataset
uspto-grants-2008_05
Patent number
US07378418B2

Reaction notes

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