Tetrahydrofuran → 1-(1-(6-(1-(2-ethoxyethyl)-1H-pyrazol-4-yl)pyridazin-3-yl)piperidin-4-yl)-6-fluoroindoline

HRID 512849Notes

Reaction equation

HRID 512849 reaction equation
[NH:1]1[CH:5]=[C:4]([C:6]2[N:11]=[N:10][C:9]([N:12]3[CH2:17][CH2:16][CH:15]([N:18]4[C:26]5[C:21](=[CH:22][CH:23]=[C:24]([F:27])[CH:25]=5)[CH2:20][CH2:19]4)[CH2:14][CH2:13]3)=[CH:8][CH:7]=2)[CH:3]=[N:2]1.[CH2:28]([O:30][CH2:31][CH2:32]Br)[CH3:29].C1COCC1.[H-].[Na+]>CCOCC.O.CN(C=O)C>[CH2:28]([O:30][CH2:31][CH2:32][N:1]1[CH:5]=[C:4]([C:6]2[N:11]=[N:10][C:9]([N:12]3[CH2:17][CH2:16][CH:15]([N:18]4[C:26]5[C:21](=[CH:22][CH:23]=[C:24]([F:27])[CH:25]=5)[CH2:20][CH2:19]4)[CH2:14][CH2:13]3)=[CH:8][CH:7]=2)[CH:3]=[N:2]1)[CH3:29]

Participants

7

Reactant 4

HCID 8028TetrahydrofuranHCID 24758Sodium hydrideHCID 611412-Bromoethyl ethyl etherHCID 896139441-(1-(6-(1H-pyrazol-4-yl)pyridazin-3-yl)piperidin-4-yl)-6-fluoroindoline

Product 1

HCID 763111101-(1-(6-(1-(2-ethoxyethyl)-1H-pyrazol-4-yl)pyridazin-3-yl)piperidin-4-yl)-6-fluoroindoline

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 21584184Diethylether waterSolvent

Procedure

To a mixture of 1-(1-(6-(1H-pyrazol-4-yl)pyridazin-3-yl)piperidin-4-yl)-6-fluoroindoline (55 mg, 0.15 mmol, 1.0 equiv) and 2-ethoxyethylbromide (0.17 mL, 1.5 mmol, 10 equiv) was added THF (2 mL) and DMF (0.5 mL). NaH (30 mg, 60% in mineral oil, 0.75 mmol, 5 equiv) was then added. The resulting mixture was stirred at room temperature for 1.5 h and then poured into Et2O/H2O (20 mL/20 mL). The organic layer was washed with brine (20 mL), dried (Na2SO4), and filtered. The solvent was removed and the resulting residue was purified by column using 90-100% EtOAc/hexane as the eluent to yield 1-(1-(6-(1-(2-ethoxyethyl)-1H-pyrazol-4-yl)pyridazin-3-yl)piperidin-4-yl)-6-fluoroindoline.

Workup

  1. washThe organic layer was washed with brine (20 mL)
  2. dry with materialdried (Na2SO4)
  3. filtrationfiltered
  4. customThe solvent was removed
  5. customthe resulting residue was purified by column

Sources & evidence

ORD record
ord-0d17f6b4a32c499f882eb99c70bb1555
Source dataset
uspto-grants-2015_08
Patent number
US09102669B2

Reaction notes

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