Dimethylformamide → Methyl 3-ethyl-4-(N-((1-methyl-1H-indazol-5-yl)methyl)sulfamoyl)benzoate

HRID 73063Notes

Reaction equation

HRID 73063 reaction equation
Br[C:2]1[CH:7]=[CH:6][C:5]([S:8]([NH:11][CH2:12][C:13]2[CH:14]=[C:15]3[C:19](=[CH:20][CH:21]=2)[N:18]([CH3:22])[N:17]=[CH:16]3)(=[O:10])=[O:9])=[C:4]([CH2:23][CH3:24])[CH:3]=1.C1(P(C2C=CC=CC=2)CCCP(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C.CN(C=O)C.C[CH2:67][O:68][C:69](C)=[O:70].CCCCCC>C([O-])(=O)C.[Pd+2].C([O-])(=O)C.CO>[CH2:23]([C:4]1[CH:3]=[C:2]([CH:7]=[CH:6][C:5]=1[S:8](=[O:10])(=[O:9])[NH:11][CH2:12][C:13]1[CH:14]=[C:15]2[C:19](=[CH:20][CH:21]=1)[N:18]([CH3:22])[N:17]=[CH:16]2)[C:69]([O:68][CH3:67])=[O:70])[CH3:24]

Participants

8

Reactant 5

HCID 6228DimethylformamideHCID 8471TriethylamineHCID 812191,3-Bis(diphenylphosphino)propane2×HCID 21226206Ethyl acetate hexaneHCID 668378224-Bromo-2-ethyl-N-((1-methyl-1H-indazol-5-yl)methyl)benzenesulfonamide

Product 1

HCID 66837911Methyl 3-ethyl-4-(N-((1-methyl-1H-indazol-5-yl)methyl)sulfamoyl)benzoateYield 64%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalyst2×HCID 887MethanolSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 4-bromo-2-ethyl-N-((1-methyl-1H-indazol-5-yl)methyl)benzenesulfonamide (prepared in step-1 of Example 4, 263 mg, 0.64 mmol), palladium(II) acetate (43 mg, 0.19 mmol), 1,3-bis(diphenylphosphino)propane (80 mg, 0.19 mmol) and triethylamine (130 mg, 1.29 mmol) in the mixture of DMF (7 mL)-MeOH (2.8 mL) was stirred at 100° C. for 1 day under carbon monooxide atmosphere. Then, to the mixture was added palladium(II) acetate (43 mg, 0.19 mmol), 1,3-bis(diphenylphosphino)propane (80 mg, 0.19 mmol). The mixture was stirred at 100° C. for 2 hrs under carbon monooxide atmosphere. The mixture was poured into EtOAc-hexane (2:1) and washed with 2 M aqueous HCl and H2O. The organic layer was dried over Na2SO4, filtered and concentrated. The residual solid was purified by silicagel column chromatography (0-40% EtOAc in hexane) to give titled compound (160 mg, 64%) as a white solid.

Workup

  1. stirringThe mixture was stirred at 100° C. for 2 hrs under carbon monooxide atmosphere
  2. washwashed with 2 M aqueous HCl and H2O
  3. dry with materialThe organic layer was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residual solid was purified by silicagel column chromatography (0-40% EtOAc in hexane)

Sources & evidence

ORD record
ord-6ac3dde0a0e44750a8f9fb4a489d5712
Source dataset
uspto-grants-2014_09
Patent number
US08829026B2

Reaction notes

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