1,2-Dichloroethane → 4-(4-Chloro-2-fluorophenyl)-N-(6-fluoro-1H-indazol-5-yl)-2-methyl-6-oxo-1,4,5,6-tetrahydro-3-pyridinecarboxamide

HRID 734695Notes

Reaction equation

HRID 734695 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][C:12](=[O:14])[NH:11][C:10]([CH3:15])=[C:9]2[C:16]([OH:18])=O)=[C:4]([F:19])[CH:3]=1.[NH2:20][C:21]1[CH:22]=[C:23]2[C:27](=[CH:28][C:29]=1[F:30])[NH:26][N:25]=[CH:24]2.C(Cl)CCl.CCN(CC)CC>CN(C=O)C.CCOC(C)=O.Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]2[CH2:13][C:12](=[O:14])[NH:11][C:10]([CH3:15])=[C:9]2[C:16]([NH:20][C:21]2[CH:22]=[C:23]3[C:27](=[CH:28][C:29]=2[F:30])[NH:26][N:25]=[CH:24]3)=[O:18])=[C:4]([F:19])[CH:3]=1

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 450905046-fluoro-1H-indazol-5-amineHCID 688260574-(4-Chloro-2-fluorophenyl)-2-methyl-6-oxo-1,4,5,6-tetrahydro-3-pyridinecarboxylic acid

Product 1

HCID 111659714-(4-Chloro-2-fluorophenyl)-N-(6-fluoro-1H-indazol-5-yl)-2-methyl-6-oxo-1,4,5,6-tetrahydro-3-pyridinecarboxamideYield 8.1%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

The product of Example 3, Step 2 (200 mg, 0.71 mmol, 1.00 equiv), 5-amino-6-fluoroindazole (107 mg, 0.71 mmol, 1.0 equiv), and EDC (162 mg, 0.85 mmol, 1.20 equiv) were suspended in 1.5 mL DMF. Et3N (0.118 mL, 0.85 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 24 mg (8%) of the title compound as an off white solid. MS (ES+) m/e 417 [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-567e5f38f8164a7f8dca0d47a55a8030
Source dataset
uspto-grants-2009_09
Patent number
US07592357B2

Reaction notes

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