Sodium hydride → 6-(2-Methyl-2 H-1,2,4-triazol-3-ylmethoxy)-3-phenyl-7-(pyrrolidin-1-vl)-1,2,4-triazolo[4,3-b]pyridazine

HRID 1383852Notes

Reaction equation

HRID 1383852 reaction equation
Cl[C:2]1[C:3]([N:17]2[CH2:21][CH2:20][CH2:19][CH2:18]2)=[CH:4][C:5]2[N:6]([C:8]([C:11]3[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=3)=[N:9][N:10]=2)[N:7]=1.[OH:22][CH2:23][C:24]1[N:25]([CH3:29])[N:26]=[CH:27][N:28]=1.[H-].[Na+]>CN(C=O)C.O>[CH3:29][N:25]1[C:24]([CH2:23][O:22][C:2]2[C:3]([N:17]3[CH2:21][CH2:20][CH2:19][CH2:18]3)=[CH:4][C:5]3[N:6]([C:8]([C:11]4[CH:16]=[CH:15][CH:14]=[CH:13][CH:12]=4)=[N:9][N:10]=3)[N:7]=2)=[N:28][CH:27]=[N:26]1

Participants

6

Reactant 3

HCID 24758Sodium hydrideHCID 11073377(1-methyl-1H-1,2,4-triazol-5-yl)methanolHCID 227441646-Chloro-3-phenyl-7-(1-pyrrolidinyl)-1,2,4-triazolo[4,3-b]pyridazine

Product 1

HCID 98859896-(2-Methyl-2 H-1,2,4-triazol-3-ylmethoxy)-3-phenyl-7-(pyrrolidin-1-vl)-1,2,4-triazolo[4,3-b]pyridazineYield 55%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 6228DimethylformamideSolvent

Procedure

To a solution of 6-chloro-3-phenyl-7-(pyrrolidin-1-yl)-1,2,4-triazolo[4,3-b]pyridazine (100 mg, 0.33 mmol) and 3-hydroxymethyl-2-methyl-1,2,4-triazole in dry DMF (5 ml) was added sodium hydride (60% dispersion in oil, 20 mg, 0.36 mmol). The mixture was stirred at room temperature for 2 hours. The reaction mixture was diluted with water (50 ml) and extracted with dichloromethane (3×25 ml). The combined extracts were washed with brine, dried over magnesium sulphate, filtered and evaporated. The solid was triturated with methanol, and collected by filtration to afford the title pyridazine (68 mg, 55%). 1H NMR (360 MHz, CDCl3) δ1.93-1.97 (4 H, m), 3.41-3.45 (4 H, m), 4.00 (3 H, s), 5.58 (2 H, s), 6.66 (1 H, s), 7.43-7.53 (3 H, m), 7.94 (1 H, s), 8.28 (2 H, d, J=8.3 Hz). MS (ES+) 377 [MH]+.

Workup

  1. extractionextracted with dichloromethane (3×25 ml)
  2. washThe combined extracts were washed with brine
  3. dry with materialdried over magnesium sulphate
  4. filtrationfiltered
  5. customevaporated
  6. customThe solid was triturated with methanol
  7. filtrationcollected by filtration

Sources & evidence

ORD record
ord-933efefd08ea47288979dbfa9c362ad9
Source dataset
uspto-grants-2001_07
Patent number
US06255305B1

Reaction notes

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