Diisopropylethylamine → N'-(5-bromopyridin-2-yl)-2-(6-chloropyridazin-3-yl)-2,2-difluoroacetohydrazide

HRID 1925136Notes

Reaction equation

HRID 1925136 reaction equation
[Cl:1][C:2]1[N:7]=[N:6][C:5]([C:8]([F:15])([F:14])[C:9]([O:11]CC)=O)=[CH:4][CH:3]=1.[Br:16][C:17]1[CH:18]=[CH:19][C:20]([NH:23][NH2:24])=[N:21][CH:22]=1.CCN(C(C)C)C(C)C>CO>[Br:16][C:17]1[CH:18]=[CH:19][C:20]([NH:23][NH:24][C:9](=[O:11])[C:8]([C:5]2[N:6]=[N:7][C:2]([Cl:1])=[CH:3][CH:4]=2)([F:14])[F:15])=[N:21][CH:22]=1

Participants

5

Reactant 3

HCID 81531DiisopropylethylamineHCID 115356995-Bromo-2-hydrazinopyridineHCID 46941483Ethyl 2-(6-chloropyridazin-3-yl)-2,2-difluoroacetate

Product 1

HCID 59233291N'-(5-bromopyridin-2-yl)-2-(6-chloropyridazin-3-yl)-2,2-difluoroacetohydrazideYield 77%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

To a solution of ethyl 2-(6-chloropyridazin-3-yl)-2,2-difluoroacetate (10.8 g, 45.6 mmol) and 5-bromo-2-hydrazinylpyridine (8.58 g, 45.6 mmol) in anhydrous MeOH (100 mL) was added DIEA (5.90 g, 45.6 mmol). The reaction was stirred at ambient temperature for 18 hrs. The solvent was removed via rotary evaporation and the resulting material was reconstituted in EtOAc. The organic phase was washed with water and concentrated to dryness. The resulting residue was purified by MPLC (EtOAc) to provide the title compound, N′-(5-bromopyridin-2-yl)-2-(6-chloropyridazin-3-yl)-2,2-difluoroacetohydrazide 45E (13.3 g, 35.1 mmol, 77% yield). 1H NMR (400 MHz, CDCl3) δ ppm 6.62 (d, J=8.84 Hz, 1 H) 7.11 (d, J=9.35 Hz, 1 H) 7.47-7.60 (m, 2 H) 8.06 (d, J=2.53 Hz, 1 H). ESI-MS:m/z 377.9 (M+H)+.

Workup

  1. customThe solvent was removed via rotary evaporation
  2. washThe organic phase was washed with water
  3. concentrationconcentrated to dryness
  4. customThe resulting residue was purified by MPLC (EtOAc)

Sources & evidence

ORD record
ord-7debc1cd7ee945158af263b135947272
Source dataset
uspto-grants-2012_05
Patent number
US08178534B2

Reaction notes

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