Chloroacetyl chloride → 2-chloro-N'-(4-(4-chlorophenyl)-5-(4-cyanophenyl)-1-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-6-oxo-1,6-dihydropyridazin-3-yl)acetohydrazide

HRID 1661103Notes

Reaction equation

HRID 1661103 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]2[C:13]([NH:14][NH2:15])=[N:12][N:11]([CH2:16][C:17]3[C:18]([CH3:27])=[N:19][C:20]([C:23]([F:26])([F:25])[F:24])=[CH:21][CH:22]=3)[C:10](=[O:28])[C:9]=2[C:29]2[CH:36]=[CH:35][C:32]([C:33]#[N:34])=[CH:31][CH:30]=2)=[CH:4][CH:3]=1.CCN(CC)CC.[Cl:44][CH2:45][C:46](Cl)=[O:47]>C1COCC1.CCOC(C)=O>[Cl:44][CH2:45][C:46]([NH:15][NH:14][C:13]1[C:8]([C:5]2[CH:6]=[CH:7][C:2]([Cl:1])=[CH:3][CH:4]=2)=[C:9]([C:29]2[CH:30]=[CH:31][C:32]([C:33]#[N:34])=[CH:35][CH:36]=2)[C:10](=[O:28])[N:11]([CH2:16][C:17]2[C:18]([CH3:27])=[N:19][C:20]([C:23]([F:25])([F:26])[F:24])=[CH:21][CH:22]=2)[N:12]=1)=[O:47]

Participants

6

Reactant 3

HCID 6577Chloroacetyl chlorideHCID 8471TriethylamineHCID 671287294-(5-(4-Chlorophenyl)-6-hydrazinyl-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-3-oxo-2,3-dihydropyridazin-4-yl)benzonitrile

Product 1

HCID 671288852-chloro-N'-(4-(4-chlorophenyl)-5-(4-cyanophenyl)-1-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-6-oxo-1,6-dihydropyridazin-3-yl)acetohydrazideYield 72%

Reagents, catalysts & solvents 2

HCID 8028TetrahydrofuranSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 4-(5-(4-chlorophenyl)-6-hydrazinyl-2-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-3-oxo-2,3-dihydropyridazin-4-yl)benzonitrile (500 mg, 0.977 mmol) in THF (7 ml), Et3N (197 mg, 1.953 mmol) was added chloroacetyl chloride (110 mg, 0.977 mmol). The reaction was stirred at room temperature for 30 min. The reaction mixture was diluted with EtOAc (50 ml) and the resulting solution was washed with water (2×20 ml) and saturated NaCl (20 ml). The organic layer was dried (MgSO4), filtered and concentrated. The residue was purified using an ISCO automated chromatography system (12 g silica gel, 20-40% EtOAc/CH2Cl2) to give the product 2-chloro-N′-(4-(4-chlorophenyl)-5-(4-cyanophenyl)-1-((2-methyl-6-(trifluoromethyl)pyridin-3-yl)methyl)-6-oxo-1,6-dihydropyridazin-3-yl)acetohydrazide as a light yellow solid (410 mg, 72% yield). HPLC retention time 2.920 min (Method A); LCMS (M+H)=587.0.

Workup

  1. washthe resulting solution was washed with water (2×20 ml) and saturated NaCl (20 ml)
  2. dry with materialThe organic layer was dried (MgSO4)
  3. filtrationfiltered
  4. concentrationconcentrated
  5. customThe residue was purified

Sources & evidence

ORD record
ord-e8de87d873624d4a9eed13df75984ad7
Source dataset
uspto-grants-2011_10
Patent number
US08030306B2

Reaction notes

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