Cesium carbonate → N-[3-bromo-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-3-chlorobenzenesulfonamide

HRID 330994Notes

Reaction equation

HRID 330994 reaction equation
[Br:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][C:9]=2Br)[N:4]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[CH:3]=1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C(=O)([O-])[O-].[Cs+].[Cs+].[Cl:68][C:69]1[CH:70]=[C:71]([S:75]([NH2:78])(=[O:77])=[O:76])[CH:72]=[CH:73][CH:74]=1>O1CCOCC1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Br:1][C:2]1[C:10]2[C:5](=[N:6][CH:7]=[CH:8][C:9]=2[NH:78][S:75]([C:71]2[CH:72]=[CH:73][CH:74]=[C:69]([Cl:68])[CH:70]=2)(=[O:77])=[O:76])[N:4]([CH2:12][O:13][CH2:14][CH2:15][Si:16]([CH3:19])([CH3:18])[CH3:17])[CH:3]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 5193773-ChlorobenzenesulfonamideHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 710902573,4-Dibromo-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrrolo[2,3-b]pyridine

Product 1

HCID 71090292N-[3-bromo-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-pyrrolo[2,3-b]pyridin-4-yl]-3-chlorobenzenesulfonamideYield 31.4%

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
100 °C

Procedure

A mixture of 3,4-dibromo-1-({[2-(trimethylsilyl)ethyl]oxy}methyl)-1H-pyrrolo[2,3-b]pyridine (D3) (1.020 g, 2.51 mmol), xantphos (0.218 g, 0.377 mmol), palladium(II) acetate (0.042 g, 0.188 mmol), cesium carbonate (1.636 g, 5.02 mmol) and 3-chlorobenzenesulfonamide (0.602 g, 3.14 mmol) in 1,4-dioxane (15 mL) was stirred at 100° C. for ca. 3 hours. The mixture was evaporated to dryness and the residues partitioned between water (15 mL) and ethyl acetate (40 mL). The aqueous phase was separated and extracted with additional ethyl acetate (15 mL). The organic extracts were combined, washed with brine (10 mL), dried with MgSO4 and evaporated to dryness. The residue was purified through silica gel, eluting with a gradient of 0-40% ethyl acetate in cyclohexane to give the title compound (407.4 mg). LCMS (A): m/z (M−H)− 514/516, C19H23BrClN3O3SSi requires 515/517 (acidic).

Workup

  1. customThe mixture was evaporated to dryness
  2. customthe residues partitioned between water (15 mL) and ethyl acetate (40 mL)
  3. customThe aqueous phase was separated
  4. extractionextracted with additional ethyl acetate (15 mL)
  5. washwashed with brine (10 mL)
  6. dry with materialdried with MgSO4
  7. customevaporated to dryness
  8. customThe residue was purified through silica gel
  9. washeluting with a gradient of 0-40% ethyl acetate in cyclohexane

Sources & evidence

ORD record
ord-a41ff08192814e358d7ed70a005e1198
Source dataset
uspto-grants-2014_11
Patent number
US08877742B2

Reaction notes

Loading…