Water → HCID 117988115, compound

HRID 2206226Notes

Reaction equation

HRID 2206226 reaction equation
[CH:1]1([N:6]2[C:14]3[CH:13]=[CH:12][N:11]=[C:10]([O:15][CH3:16])[C:9]=3[C:8]([C:17]3[CH:18]=[C:19]([C:22]([NH2:24])=[O:23])[S:20][CH:21]=3)=[N:7]2)[CH2:5][CH2:4][CH2:3][CH2:2]1.[Cl:25]N1C(=O)CCC1=O.O>CN(C=O)C>[Cl:25][C:13]1[C:14]2[N:6]([CH:1]3[CH2:2][CH2:3][CH2:4][CH2:5]3)[N:7]=[C:8]([C:17]3[CH:18]=[C:19]([C:22]([NH2:24])=[O:23])[S:20][CH:21]=3)[C:9]=2[C:10]([O:15][CH3:16])=[N:11][CH:12]=1

Participants

5

Reactant 3

HCID 962WaterHCID 31398Chlorosuccinimide3×HCID 117987637HCID 117987637, compound

Product 1

HCID 117988115HCID 117988115, compoundYield 58.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 4-(1-cyclopentyl-4-methoxy-1H-pyrazolo[4,3-c]pyridin-3-yl)thiophene-2-carboxamide (30.3 mg) obtained in Step A of Example 286 in DMF (2 mL) was added N-chlorosuccinimide (13.0 mg) at 0° C., and the mixture was stirred overnight at 80° C. To the reaction mixture was added N-chlorosuccinimide (6.0 mg), and the mixture was stirred at 80° C. for 3 hr. To the reaction mixture was added N-chlorosuccinimide (6.0 mg), and the mixture was stirred at 80° C. for 3 hr. To the reaction mixture was added water, and the mixture was extracted with ethyl acetate. The organic layer was washed successively with water and saturated brine, dried over anhydrous sodium sulfate, and concentrated under reduced pressure. The residue was purified by silica gel column chromatography (ethyl acetate/hexane), and then HPLC (column: L-column2 ODS (trade name) 20 mmID×150 mmL, 5 μm, manufactured by Daicel Chemical Industries, mobile phase: water/acetonitrile (containing 10 mM ammonium carbonate)) to give the title compound (19.5 mg).

Workup

  1. stirringthe mixture was stirred at 80° C. for 3 hr
  2. stirringthe mixture was stirred at 80° C. for 3 hr
  3. extractionthe mixture was extracted with ethyl acetate
  4. washThe organic layer was washed successively with water and saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified by silica gel column chromatography (ethyl acetate/hexane)

Sources & evidence

ORD record
ord-dafbe96be2d74ab2bae38026e3bf9ecd
Source dataset
uspto-grants-2016_06
Patent number
US09371320B2

Reaction notes

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