1,2-Dichloroethane → HCID 178429244, compound

HRID 734712Notes

Reaction equation

HRID 734712 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])[N:15]([CH3:19])[C:14]([CH3:20])=[C:13]1[C:21]([O:23]C)=O.[NH2:25][C:26]1[CH:27]=[C:28]2[C:32](=[CH:33][CH:34]=1)[NH:31][N:30]=[C:29]2[Cl:35].C(Cl)CCl.CCN(CC)CC>CN(C=O)C.CCOC(C)=O.Cl>[Cl:35][C:29]1[C:28]2[C:32](=[CH:33][CH:34]=[C:26]([NH:25][C:21]([C:13]3[CH:12]([C:3]4[CH:4]=[CH:5][C:6]([C:8]([F:9])([F:10])[F:11])=[CH:7][C:2]=4[F:1])[CH2:17][C:16](=[O:18])[N:15]([CH3:19])[C:14]=3[CH3:20])=[O:23])[CH:27]=2)[NH:31][N:30]=1

Participants

8

Reactant 4

HCID 111,2-DichloroethaneHCID 8471TriethylamineHCID 68827826Methyl 4-[2-fluoro-4-(trifluoromethyl)phenyl]-1,2-dimethyl-6-oxo-1,4,5,6-tetrahydro-3-pyridinecarboxylateHCID 178507360HCID 178507360, compound

Product 1

HCID 178429244HCID 178429244, compoundYield 7%

Reagents, catalysts & solvents 3

HCID 313Hydrochloric AcidSolventHCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

The product of Example 45, Step 1 (150 mg, 0.453 mmol, 1.00 equiv), 5-amino-3-chloroindazole (76 mg, 0.453 mmol, 1.0 equiv), and EDC (104 mg, 0.543 mmol, 1.20 equiv) were suspended in 1.0 mL DMF. Et3N (0.076 mL, 0.543 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 (0-80% EtOAc in Hexanes) and further purified by reverse-phase HPLC (30-80% CH3CN/H2O—NH4OH to pH 10 over 27 minutes, retention time 13.98 min) to provide 15 mg (7%) of the title compound as a white solid. MS (ES+) m/e 481 [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 (0-80% EtOAc in Hexanes)
  7. customfurther purified by reverse-phase HPLC (30-80% CH3CN/H2O—NH4OH to pH 10 over 27 minutes, retention time 13.98 min)

Sources & evidence

ORD record
ord-83bc38d1136144df87d160aa5b45fd34
Source dataset
uspto-grants-2009_09
Patent number
US07592357B2

Reaction notes

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