N,N'-Dimethylethylenediamine → 1-(4-Fluoro-phenyl)-1H-indazole-4-carboxylic acid (6-methanesulfonyl-pyridin-3-ylmethyl)-amide

HRID 1677688Notes

Reaction equation

HRID 1677688 reaction equation
Br[C:2]1[N:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]([C:12]2[C:13]3[CH:14]=[N:15][N:16]([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)[C:17]=3[CH:18]=[CH:19][CH:20]=2)=[O:11])=[CH:4][CH:3]=1.[CH3:28][S:29]([O-:31])=[O:30].[Na+].CNCCNC>CCOC(C)=O.[O-]S(C(F)(F)F)(=O)=O.[Cu+2].[O-]S(C(F)(F)F)(=O)=O>[CH3:28][S:29]([C:2]1[N:7]=[CH:6][C:5]([CH2:8][NH:9][C:10]([C:12]2[C:13]3[CH:14]=[N:15][N:16]([C:21]4[CH:26]=[CH:25][C:24]([F:27])=[CH:23][CH:22]=4)[C:17]=3[CH:18]=[CH:19][CH:20]=2)=[O:11])=[CH:4][CH:3]=1)(=[O:31])=[O:30]

Participants

6

Reactant 3

HCID 8070N,N'-DimethylethylenediamineHCID 2733271Sodium methanesulfinateHCID 444696611-(4-Fluoro-phenyl)-1H-indazole-4-carboxylic acid (6-bromo-pyridin-3-ylmethyl)-amide

Product 1

HCID 444698041-(4-Fluoro-phenyl)-1H-indazole-4-carboxylic acid (6-methanesulfonyl-pyridin-3-ylmethyl)-amide

Reagents, catalysts & solvents 2

HCID 2734996copper(II) trifluoromethanesulfonateCatalystHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
100 °C

Procedure

A microwave tube was charged with 1-(4-fluoro-phenyl)-1H-indazole-4-carboxylic acid (6-bromo-pyridin-3-ylmethyl)-amide (650 mg, 1.5 mmol), copper(II) triflate (550 mg, 1.5 mmol) and sodium methanesulfinate (230 mg, 2.3 mmol). The flask was sealed, evacuated and purged (3 times) with nitrogen. The solids were taken up in DMSO (5 mL) and N,N′-dimethylethylene diamine (0.490 mL, 4.59 mmol) was added. The solution was stirred at 100° C. After 16 hours, the mixture was diluted with EtOAc (10 mL) and washed with saturated aqueous NH4Cl (5 mL), saturated aqueous NaHCO3 (5 mL) and brine (5 mL). The organic layer was dried over MgSO4, filtered through diatomaceous earth and concentrated. The residue was purified by silica gel chromatography eluting with a gradient of 0-80% ethyl acetate in hexanes. Fractions containing the product were pooled and further purified by silica gel chromatography eluting with a gradient of 0-60% ethyl acetate in hexanes. Desired fractions were pooled and concentrated, and the solid was triturated with hexanes (10 mL) to afford the title compound as a white solid.

Workup

  1. customThe flask was sealed
  2. customevacuated
  3. custompurged (3 times) with nitrogen
  4. washwashed with saturated aqueous NH4Cl (5 mL), saturated aqueous NaHCO3 (5 mL) and brine (5 mL)
  5. dry with materialThe organic layer was dried over MgSO4
  6. filtrationfiltered through diatomaceous earth
  7. concentrationconcentrated
  8. customThe residue was purified by silica gel chromatography
  9. washeluting with a gradient of 0-80% ethyl acetate in hexanes
  10. additionFractions containing the product
  11. customfurther purified by silica gel chromatography
  12. washeluting with a gradient of 0-60% ethyl acetate in hexanes
  13. concentrationconcentrated
  14. customthe solid was triturated with hexanes (10 mL)

Sources & evidence

ORD record
ord-92576a4671e94af6a1c0328c0dccc270
Source dataset
uspto-grants-2011_08
Patent number
US08008327B2

Reaction notes

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