Sodium hydride → HCID 22609931, compound

HRID 1369424Notes

Reaction equation

HRID 1369424 reaction equation
[H-].[Na+].[CH3:3][N:4]1[C:8]([CH2:9][OH:10])=[N:7][CH:6]=[N:5]1.Cl[C:12]1[C:13]([C:29]2([CH3:35])[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]2)=[CH:14][C:15]2[N:16]([C:18]([C:21]3[CH:26]=[CH:25][C:24]([F:27])=[CH:23][C:22]=3[F:28])=[N:19][N:20]=2)[N:17]=1>CN(C)C=O>[F:28][C:22]1[CH:23]=[C:24]([F:27])[CH:25]=[CH:26][C:21]=1[C:18]1[N:16]2[N:17]=[C:12]([O:10][CH2:9][C:8]3[N:4]([CH3:3])[N:5]=[CH:6][N:7]=3)[C:13]([C:29]3([CH3:35])[CH2:34][CH2:33][CH2:32][CH2:31][CH2:30]3)=[CH:14][C:15]2=[N:20][N:19]=1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 11073377(1-methyl-1H-1,2,4-triazol-5-yl)methanolHCID 22609916HCID 22609916, compound

Product 1

HCID 22609931HCID 22609931, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Procedure

Sodium hydride (60% dispersion in oil, 13 mg, 0.33 mmol) was added to a stirred solution of (2-methyl-2H-1,2,4-triazol-3-yl)methanol (prepared using the conditions described in EP-A-421210; 37 mg, 0.33 mmol) in anhydrous N,N-dimethylformamide (5 ml) at room temperature under nitrogen. This was stirred for 30 mins and 6-chloro-3-(2,4-difluorophenyl)-7-(1-methylcyclohexyl)-1,2,4-triazolo[4,3-b]pyridazine (100 mg, 0.275 mmol) in N,N-dimethylformamide (3 ml) was then added and the mixture stirred for a further 60 minutes. The reaction was quenched with water (20 ml) and stirred for an additional 60 minutes. The precipitated solid was collected by filtration and washed with water. The solid was dissolved in dichloromethane (20 ml), filtered and evaporated. The residue was recrystallised from ethyl acetate/hexane to give the title compound (38 mg): m.p.=196° C.; 1H NMR (360 MHz, CDCl3) δ1.32 (3H, s), 1.33-1.66 (6H, m), 1.72-1.81 (2H, m), 1.93-2.03 (2H, m), 3.87 (3H, s), 5.50 (2H, s), 7.00-7.14 (2H, m), 7.83-7.90 (1H, m), 7.91 (1H, s), 8.00 (1H, s MS (ES+) m/e 440 [MH]+; Anal. Found: C, 59.74; H, 5.23; N, 22.10. C22H23F2N7O requires: C, 60.13; H, 5.27; N, 22.31%.

Workup

  1. customprepared
  2. customat room temperature
  3. stirringthe mixture stirred for a further 60 minutes
  4. customThe reaction was quenched with water (20 ml)
  5. stirringstirred for an additional 60 minutes
  6. filtrationThe precipitated solid was collected by filtration
  7. washwashed with water
  8. dissolutionThe solid was dissolved in dichloromethane (20 ml)
  9. filtrationfiltered
  10. customevaporated
  11. customThe residue was recrystallised from ethyl acetate/hexane

Sources & evidence

ORD record
ord-f424319a242a4a55877cb29d8ae5438f
Source dataset
uspto-grants-2003_06
Patent number
US06579875B1

Reaction notes

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