Sodium hydride → HCID 9929611, compound

HRID 1596200Notes

Reaction equation

HRID 1596200 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]([N:27]2[CH2:31][CH2:30][CH2:29][CH2:28]2)=[CH:14][C:15]2[N:16]([C:18]([C:21]3[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=3)=[N:19][N:20]=2)[N:17]=1>CN(C=O)C>[CH3:3][N:4]1[C:8]([CH2:9][O:10][C:12]2[C:13]([N:27]3[CH2:31][CH2:30][CH2:29][CH2:28]3)=[CH:14][C:15]3[N:16]([C:18]([C:21]4[CH:22]=[N:23][CH:24]=[CH:25][CH:26]=4)=[N:19][N:20]=3)[N:17]=2)=[N:7][CH:6]=[N:5]1

Participants

5

Reactant 3

HCID 24758Sodium hydrideHCID 10979520HCID 10979520, compoundHCID 11073377(1-methyl-1H-1,2,4-triazol-5-yl)methanol

Product 1

HCID 9929611HCID 9929611, compoundYield 60.2%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

Sodium hydride (60% dispersion in oil, 16 mg, 0.41 mmol) was added to a solution of (2-methyl-2H-1,2,4-triazol-3-yl)methanol (EP-A-421210; 40 mg, 0.35 mmol) in dry DMF (2 ml) at room temperature. After 1 h at room temperature a solution of 6-chloro-3-(pyridin-3-yl)-7-(pyrrolidin-1-yl)-1,2,4-triazolo[4,3-b]pyridazine (100 mg, 0.33 mmol) was added and the reaction stirred for 18 h. The residue was partitioned between dichloromethane and water. The aqueous was further extracted with dichloromethane (2×100 ml). The combined extracts were dried (Na2SO4), filtered and evaporated. The residue was purified by chromatography on silica gel, eluting with 0-10% ethyl acetate-methanol to afford the title pyridazine (75 mg, 60%). 1H NMR (250 MHz, CDCl3) 1.99-2.04 (4H, m), 3.52-3.57 (4H, m), 4.01 (3H, s), 5.65 (2H, s), 6.69 (1H, s), 7.57 (1H, q, J=7.7, 4.8 Hz), 7.97 (1H, s), 8.60-8.68 (2H, m), 9.51 (1H, d, J=1.6 Hz); MS (ES+) 378 [MH]+.

Workup

  1. customThe residue was partitioned between dichloromethane and water
  2. extractionThe aqueous was further extracted with dichloromethane (2×100 ml)
  3. dry with materialThe combined extracts were dried (Na2SO4)
  4. filtrationfiltered
  5. customevaporated
  6. customThe residue was purified by chromatography on silica gel
  7. washeluting with 0-10% ethyl acetate-methanol

Sources & evidence

ORD record
ord-559c918ea37f42729aa59a9b93dd2734
Source dataset
uspto-grants-2001_09
Patent number
US06291460B1

Reaction notes

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