Dimethylformamide → 2-cyclopropylmethyl-6-(3-fluoro-4-methoxyphenyl)-4-[3-(4-methyl-1-piperazinyl)propyl]-2H-pyridazin-3-one

HRID 982811

Reaction equation

HRID 982811 reaction equation
[CH:1]1([CH2:4][N:5]2[C:10](=[O:11])[C:9]([CH2:12][CH:13](C(OC(C)(C)C)=O)[C:14](OC(C)(C)C)=O)=[CH:8][C:7]([C:28]3[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[C:30]([F:36])[CH:29]=3)=[N:6]2)[CH2:3][CH2:2]1.[H-].[Na+].C(OC(C)(C)C)(=O)CC(OC(C)(C)C)=O.BrC[C:56]1[C:57](=O)[N:58]([CH2:71][CH:72]2CC2)N=C(C2C=CC(OC)=C(F)C=2)C=1.[CH3:76][N:77](C)C=O>O>[CH:1]1([CH2:4][N:5]2[C:10](=[O:11])[C:9]([CH2:12][CH2:13][CH2:14][N:58]3[CH2:57][CH2:56][N:77]([CH3:76])[CH2:72][CH2:71]3)=[CH:8][C:7]([C:28]3[CH:33]=[CH:32][C:31]([O:34][CH3:35])=[C:30]([F:36])[CH:29]=3)=[N:6]2)[CH2:3][CH2:2]1

Participants

7

Reactant 5

HCID 6228DimethylformamideHCID 24758Sodium hydrideHCID 68324Di-tert-butyl malonateHCID 219916102-cyclopropylmethyl-4-[2,2-di(tert-butoxycarbonyl)ethyl]-6-(3-fluoro-4-methoxyphenyl)-2H-pyridazin-3-oneHCID 219917104-bromomethyl-2-cyclopropylmethyl-6-(3-fluoro-4-methoxyphenyl)-2H-pyridazin-3-one

Product 1

HCID 101365362-cyclopropylmethyl-6-(3-fluoro-4-methoxyphenyl)-4-[3-(4-methyl-1-piperazinyl)propyl]-2H-pyridazin-3-oneYield 61.8%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Procedure

Preparation of 2-cyclopropylmethyl-4-[2,2-di(tert-butoxycarbonyl)ethyl]-6-(3-fluoro-4-methoxyphenyl)-2H-pyridazin-3-one After 55% sodium hydride (322 mg, 7.38 mmol) was added to a solution of di-tert-butyl malonate (970 mg, 4.48 mmol) in N,N-dimethylformamide (10 mL), 4-bromomethyl-2-cyclopropylmethyl-6-(3-fluoro-4-methoxyphenyl)-2H-pyridazin-3-one (1.8 g, 4.90 mmol) was added under ice-cold stirring. The reaction mixture was stirred at room temperature for 1 hour, poured into water, and extracted with ethyl acetate. The extract was washed with brine and dried over anhydrous sodium sulfate. The solvent was distilled off under reduced pressure. The residue was isolated and purified by chromatography on silica gel (hexane/ethyl acetate=3/1) to yield the title compound as a yellow powder (yield: 1.39 mg, 61.8%).

Workup

  1. additionwas added under ice-cold stirring
  2. extractionextracted with ethyl acetate
  3. washThe extract was washed with brine
  4. dry with materialdried over anhydrous sodium sulfate
  5. distillationThe solvent was distilled off under reduced pressure
  6. customThe residue was isolated
  7. custompurified by chromatography on silica gel (hexane/ethyl acetate=3/1)

Sources & evidence

ORD record
ord-1af5c84cab6a44b4808bd19f6edcba22
Source dataset
uspto-grants-2005_03
Patent number
US06861428B2

Linked notes

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