1,2-Dichloroethane → 4-[2-Fluoro-4-(trifluoromethyl)phenyl]-2-methyl-N-(3-methyl-1H-indazol-5-yl)-6-oxo-1,4,5,6-tetrahydro-3-pyridinecarboxamide

HRID 734687Notes

Reaction equation

HRID 734687 reaction equation
[F:1][C:2]1[CH:7]=[C:6]([C:8]([F:11])([F:10])[F:9])[CH:5]=[CH:4][C:3]=1[CH:12]1[CH2:17][C:16](=[O:18])[NH:15][C:14]([CH3:19])=[C:13]1[C:20](O)=[O:21].[NH2:23][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[NH:29][N:28]=[C:27]2[CH3:33].C(Cl)CCl.CCN(CC)CC>CN(C=O)C.CCOC(C)=O.Cl>[F:1][C:2]1[CH:7]=[C:6]([C:8]([F:9])([F:10])[F:11])[CH:5]=[CH:4][C:3]=1[CH:12]1[CH2:17][C:16](=[O:18])[NH:15][C:14]([CH3:19])=[C:13]1[C:20]([NH:23][C:24]1[CH:25]=[C:26]2[C:30](=[CH:31][CH:32]=1)[NH:29][N:28]=[C:27]2[CH3:33])=[O:21]

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 688271204-[2-Fluoro-4-(trifluoromethyl)phenyl]-2-methyl-6-oxo-1,4,5,6-tetrahydro-3-pyridinecarboxylic acidHCID 178434299HCID 178434299, compound

Product 1

HCID 1784292344-[2-Fluoro-4-(trifluoromethyl)phenyl]-2-methyl-N-(3-methyl-1H-indazol-5-yl)-6-oxo-1,4,5,6-tetrahydro-3-pyridinecarboxamideYield 23.1%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

The product of Example 21, Step 2 (200 mg, 0.63 mmol, 1.00 equiv), 5-amino-3-methylindazole (93 mg, 0.63 mmol, 1.0 equiv), and EDC (145 mg, 0.757 mmol, 1.20 equiv) were suspended in 1.75 mL DMF. Et3N (0.106 mL, 0.757 mmol, 1.2 equiv) was added and the solution was stirred at room temperature for 18 hrs. The reaction mixture was diluted with EtOAc and 1N HCl. The phases were separated, and the organic phase was washed twice with 1N HCl, once with satd. NaHCO3, and once with satd. NaCl. The organic phase was dried over Na2SO4, filtered, and concentrated en vacuo. The residue was purified by flash chromatography (20-100% EtOAc in Hexanes) to provide 65 mg (23%) of the title compound as an off white solid. MS (ES+) m/e 447 [M+H]+

Workup

  1. customThe phases were separated
  2. washthe organic phase was washed twice with 1N HCl, once with satd
  3. dry with materialThe organic phase was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated en vacuo
  6. customThe residue was purified by flash chromatography (20-100% EtOAc in Hexanes)

Sources & evidence

ORD record
ord-907d2be618f042b98a64b15d0606d7a1
Source dataset
uspto-grants-2009_09
Patent number
US07592357B2

Reaction notes

Loading…