Sodium hydride → 3-(2-Fluorophenyl)-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-7-(thien-2-yl)-1,2,4-triazolo[4,3-b]pyridazine

HRID 2306587Notes

Reaction equation

HRID 2306587 reaction equation
[CH3:1][N:2]1[C:6]([CH2:7][OH:8])=[N:5][CH:4]=[N:3]1.[H-].[Na+].Cl[C:12]1[C:13]([C:28]2[S:29][CH:30]=[CH:31][CH:32]=2)=[CH:14][C:15]2[N:16]([C:18]([C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][C:22]=3[F:27])=[N:19][N:20]=2)[N:17]=1>CN(C=O)C.O>[F:27][C:22]1[CH:23]=[CH:24][CH:25]=[CH:26][C:21]=1[C:18]1[N:16]2[N:17]=[C:12]([O:8][CH2:7][C:6]3[N:2]([CH3:1])[N:3]=[CH:4][N:5]=3)[C:13]([C:28]3[S:29][CH:30]=[CH:31][CH:32]=3)=[CH:14][C:15]2=[N:20][N:19]=1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 11073377(1-methyl-1H-1,2,4-triazol-5-yl)methanolHCID 226098966-Chloro-3-(2-fluorophenyl)-7-(thien-2-yl)-1,2,4-triazolo[4,3-b]pyridazine

Product 1

HCID 226099153-(2-Fluorophenyl)-6-(2-methyl-2H-1,2,4-triazol-3-ylmethoxy)-7-(thien-2-yl)-1,2,4-triazolo[4,3-b]pyridazine

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of (2-methyl-2H-1,2,4-triazol-3-yl)methanol (0.11 g, 1.0 mmol) (prepared using the conditions described in EP-A-421210) in DMF (5 ml) was added sodium hydride (0.04 g of a 60% dispersion in oil, 1 mol eq) and the reaction mixture was stirred at room temperature for 30 min. After this time 6-chloro-3-(2-fluorophenyl)-7-(thien-2-yl)-1,2,4-triazolo[4,3-b]pyridazine (0.19 g, 0.57 mmol) was added and the reaction mixture was stirred at room temperature for 18 h. The reaction mixture was diluted with water (70 ml) and the precipitate was collected. The solid was purified by boiling in ethyl acetate and collecting the title compound as a yellow solid (0.01 g, 12%). 1H NMR (250 MHz, d6-DMSO) δ 3.83 (3H, s), 5.64 (2H, s), 7.24 (1H, dd, J 4 and 4 Hz), 7.44-7.55 (2H, m), 7.66-7.71 (1H, m), 7.82 (1H, d, J=5 Hz), 7.96-8.01 (3H, m), 8.23 (1H, s). MS (ES+) m/e 408 [MH]+. Anal. Found C, 53.81; H, 3.62; N, 23.42%. C19H14FN7OS.0.9(H2O) requires C, 53.87; H, 3.76; N, 23.14% m.p. 189-190° C.

Workup

  1. stirringthe reaction mixture was stirred at room temperature for 18 h
  2. customthe precipitate was collected
  3. customThe solid was purified
  4. customcollecting the title compound as a yellow solid (0.01 g, 12%)

Sources & evidence

ORD record
ord-ab9f4f2c95774b7c907423494f2f75f2
Source dataset
uspto-grants-2004_12
Patent number
US06828322B2

Reaction notes

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