Water → HCID 19437750, compound

HRID 1734519Notes

Reaction equation

HRID 1734519 reaction equation
[CH2:1]([N:8]1[C:12]2=[C:13]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[N:14]=[N:15][CH:16]=[C:11]2[C:10](Br)=[C:9]1[CH3:27])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.C([Li])CCC.CN(C)[CH:35]=[O:36].O>O1CCCC1.CCCCCC>[CH2:1]([N:8]1[C:12]2=[C:13]([O:17][CH2:18][C:19]3[CH:24]=[CH:23][C:22]([F:25])=[CH:21][CH:20]=3)[N:14]=[N:15][CH:16]=[C:11]2[C:10]([CH:35]=[O:36])=[C:9]1[CH3:27])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

7

Reactant 4

HCID 962WaterHCID 6228DimethylformamideHCID 194377591-Benzyl-3-bromo-7-(4-fluorobenzyloxy)-2-methylpyrrolo[2,3-d]pyridazineHCID 178418339Butyllithium

Product 1

HCID 19437750HCID 19437750, compound

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8058HexaneSolvent

Conditions

Temperature
-70 °C

Procedure

A solution of 810 mg (1.9 mmol) of 1-benzyl-3-bromo-7-(4-fluorobenzyloxy)-2-methylpyrrolo[2,3-d]pyridazine in 30 ml of anhydrous tetrahydrofuran is cooled to -70° C. under argon and treated with 1.65 ml (2.7 mmol) of a 15% strength solution of n-butyllithium in hexane. The mixture is subsequently stirred at -70° C. for a further 30 min. After addition of 215 μl (2.7 mmol) of anhydrous dimethylformamide, the temperature is kept at -70° C. for a further 30 min and subsequently slowly increased to 20° C. The solution is then treated with 100 ml of water and extracted with 3×50 ml of ethyl acetate. The organic extracts are washed with 50 ml of water, dried over magnesium sulfate and concentrated. The residue which remains is chromatographed on silica gel (eluent: ethyl acetate). After concentration of the fractions of Rf=0.4 and crystallization from diisopropyl ether, 150 mg (21%) of the title compound are isolated. M.p.: 136°-141° C.

Workup

  1. waitthe temperature is kept at -70° C. for a further 30 min
  2. temperaturesubsequently slowly increased to 20° C
  3. extractionextracted with 3×50 ml of ethyl acetate
  4. washThe organic extracts are washed with 50 ml of water
  5. dry with materialdried over magnesium sulfate
  6. concentrationconcentrated
  7. customThe residue which remains is chromatographed on silica gel (eluent: ethyl acetate)
  8. customAfter concentration of the fractions of Rf=0.4 and crystallization from diisopropyl ether, 150 mg (21%) of the title compound
  9. customare isolated

Sources & evidence

ORD record
ord-05ef312851ee4d18bbe8b953987564da
Source dataset
uspto-grants-1996_07
Patent number
US05534515

Reaction notes

Loading…