Sodium hydride → HCID 22609942, compound

HRID 1369431Notes

Reaction equation

HRID 1369431 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:29]2[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=O)C>[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]([N:29]3[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 22609939HCID 22609939, compound

Product 1

HCID 22609942HCID 22609942, compoundYield 30%

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 (prepared using the conditions described in EP-A-421210) (38 mg, 0.33 mmol) in dry DMF (2 ml) at room temperature. After 1 h at room temperature a solution of 6-chloro-3-(2,4-difluorophenyl)-7-(pyrrolidin-1-yl)-1,2,4-triazolo[4,3-b]pyridazine (102 mg, 0.30 mmol) was added and the reaction stirred for 18 hours. 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 0-2% ethyl acetate-methanol to afford the title pyridazine (42 mg, 30%). 1H NMR (250 MHz, CDCl3) 1.73-1.78 (4H, m), 3.51-3.55 (4H, m), 3.93 (3H, s), 5.40 (2H, s), 6.65 (1H, s), 6.95-7.03 (2H, m), 7.92-7.94 (1H, m), 8.04 (1H, s), MS (ES+) 413 [MH]+.

Workup

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

Sources & evidence

ORD record
ord-0267d437508d4a419c4376766010ebcf
Source dataset
uspto-grants-2003_06
Patent number
US06579875B1

Reaction notes

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