Triethylamine → 6-Bromo-2-(1-methyl-1H-pyrazol-4-yl)-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridine

HRID 2205861Notes

Reaction equation

HRID 2205861 reaction equation
[C:1]([C:3]1[CH:4]=[N:5][N:6]([CH3:8])[CH:7]=1)#[CH:2].[Br:9][C:10]1[CH:15]=[C:14]([NH:16][S:17]([CH3:20])(=[O:19])=[O:18])[C:13](I)=[CH:12][N:11]=1.C(N(CC)CC)C>CN(C=O)C.[Cu]I.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Br:9][C:10]1[N:11]=[CH:12][C:13]2[CH:2]=[C:1]([C:3]3[CH:4]=[N:5][N:6]([CH3:8])[CH:7]=3)[N:16]([S:17]([CH3:20])(=[O:19])=[O:18])[C:14]=2[CH:15]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 511383214-Ethynyl-1-methyl-1H-pyrazoleHCID 86706267N-(2-Bromo-5-iodopyridin-4-yl)methanesulfonamide

Product 1

HCID 867062756-Bromo-2-(1-methyl-1H-pyrazol-4-yl)-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridineYield 45.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

4-Ethynyl-1-methyl-1H-pyrazole (20) (4.11 g, 38.7 mmole) was dissolved in DMF (95 mL) and N-(2-bromo-5-iodopyridin-4-yl)methanesulfonamide 8 (12.18 g 32.3 mmole) was added. To the solution was added triethylamine (19.6 mL, 14.1 g 139 mmole) and copper(I) iodide (214 mg 1.12 mmole). The reaction was sealed and flushed with nitrogen. Bis(triphenylphosphine)palladium dichloride (797 mg 1.13 mmole) was added and the reaction was again flushed with nitrogen and heated at 60° C. for 105 minutes. Most of the DMF was evaporated and the residue taken up in ethyl acetate (350 ml). The solution was washed with water (3×100 mL) and brine. Each aqueous fraction was backwashed with the same 100 mL portion of ethyl acetate. The combined organics were dried and evaporated. The residue was flash chromatographed (silica) eluting with dichloromethane, 1:4 ethyl acetate:dichloromethane, 1:1 ethyl acetate:dichloromethane and ethyl acetate to give the title compound (5.19 g 45.9%). 1H-NMR (CDCl3, 500 MHz): δ 2.98 (s, 3H), 4.01 (s, 3H), 6.69 (d, J=0.95 Hz, 1H), 7.73 (s, 1H), 7.78 (s, 1H), 8.25 (t, J=0.95 Hz, 1H), 8.64 (d, J=0.95 Hz, 1H).

Workup

  1. customThe reaction was sealed
  2. customflushed with nitrogen
  3. customthe reaction was again flushed with nitrogen
  4. customMost of the DMF was evaporated
  5. washThe solution was washed with water (3×100 mL) and brine
  6. customThe combined organics were dried
  7. customevaporated
  8. customchromatographed (silica)
  9. washeluting with dichloromethane, 1:4 ethyl acetate

Sources & evidence

ORD record
ord-4a03c7bfad664da69167b26f1a4aebe3
Source dataset
uspto-grants-2016_06
Patent number
US09371319B2

Reaction notes

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