Pyridine → 4-bromomethyl-2-cyclopropylmethyl-6-(3-fluoro-4-methoxyphenyl)-2H-pyridazin-3-one

HRID 1348778Notes

Reaction equation

HRID 1348778 reaction equation
[CH:1]1([CH2:4][N:5]2[C:10](=[O:11])[C:9]([CH2:12]O)=[CH:8][C:7]([C:14]3[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([F:22])[CH:15]=3)=[N:6]2)[CH2:3][CH2:2]1.C(Br)(Br)(Br)[Br:24].N1C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>O1CCCC1>[Br:24][CH2:12][C:9]1[C:10](=[O:11])[N:5]([CH2:4][CH:1]2[CH2:3][CH2:2]2)[N:6]=[C:7]([C:14]2[CH:19]=[CH:18][C:17]([O:20][CH3:21])=[C:16]([F:22])[CH:15]=2)[CH:8]=1

Participants

6

Reactant 4

HCID 1049PyridineHCID 11205Carbon tetrabromideHCID 11776TriphenylphosphineHCID 219916432-cyclopropylmethyl-6-(3-fluoro-4-methoxyphenyl)-4-hydroxymethyl-2H-pyridazin-3-one

Product 1

HCID 219917104-bromomethyl-2-cyclopropylmethyl-6-(3-fluoro-4-methoxyphenyl)-2H-pyridazin-3-oneYield 69.5%

Reagents, catalysts & solvents 1

HCID 8028TetrahydrofuranSolvent2×

Procedure

2-Cyclopropylmethyl-6-(3-fluoro-4-methoxyphenyl)-4-hydroxymethyl-2H-pyridazin-3-one (185 mg, 0.61 mmol), carbon tetrabromide (404 mg, 1.2 mmol) and pyridine (48 mg, 0.61 mmol) were dissolved in tetrahydrofuran (3 mL), and under ice-cold stirring, a solution of triphenylphosphine (319 mg, 1.2 mmol) in tetrahydrofuran (3 mL) was added. Under ice cooling, the mixture was stirred for 1 hour, and further stirred at room temperature. Insoluble materials were filtered off, the solvent was distilled off under reduced pressure, and the residue was isolated and purified by column chromatography on silica gel (hexane/ethyl acetate=2/1) to yield the title compound as a yellow powder (yield: 155 mg, 69.5%).

Workup

  1. stirringfurther stirred at room temperature
  2. filtrationInsoluble materials were filtered off
  3. distillationthe solvent was distilled off under reduced pressure
  4. customthe residue was isolated
  5. custompurified by column chromatography on silica gel (hexane/ethyl acetate=2/1)

Sources & evidence

ORD record
ord-333717e0bb544534a877158b4bc3d3a6
Source dataset
uspto-grants-2007_05
Patent number
US07211577B2

Reaction notes

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