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

HRID 2205859Notes

Reaction equation

HRID 2205859 reaction equation
[Cl:1][C:2]1[CH:7]=[C:6]([NH:8]S(C)(=O)=O)[C:5](I)=[CH:4][N:3]=1.[C:14]([C:16]1[CH:17]=[N:18][N:19](C(OC(C)(C)C)=O)[CH:20]=1)#[CH:15].C(N(CC)CC)C.C1CCN2C(=NCCC2)CC1.[NH4+].[Cl-]>CN(C=O)C.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.[Cu](I)I>[Cl:1][C:2]1[N:3]=[CH:4][C:5]2[CH:15]=[C:14]([C:16]3[CH:17]=[N:18][NH:19][CH:20]=3)[NH:8][C:6]=2[CH:7]=1

Participants

9

Reactant 5

HCID 8471TriethylamineHCID 25517Ammonium ChlorideHCID 811841,8-Diazabicyclo(5.4.0)undec-7-ene2×HCID 45382264tert-butyl 4-ethynyl-1H-pyrazole-1-carboxylateHCID 86706272N-(2-Chloro-5-iodopyridin-4-yl)methanesulfonamide

Product 1

HCID 867062746-Chloro-2-(1H-pyrazol-4-yl)-1H-pyrrolo[3,2-c]pyridineYield 71.1%

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

Bis(triphenylphosphine)palladium dichloride (23.30 mg, 0.033 mmol) was added to a solution of N-(2-chloro-5-iodopyridin-4-yl)methanesulfonamide (14) (276.0 mg, 0.83 mmol), tert-butyl 4-ethynyl-1H-pyrazole-1-carboxylate (4) (239.0 mg, 1.24 mmol), triethylamine (521 μL, 3.73 mmol) and copper iodide (7.90 mg, 0.041 mmol) in anhydrous DMF (3.0 mL). The reaction mixture was heated at 60° C. for 1 h under microwave irradiation (absorption:normal). To this reaction mixture, DBU (0.51 mL, 3.36 mmol) was added and the microwave vial was placed in an oil-bath preheated at 100° C., and then stirred at this temperature for 2.5 h. More DBU (0.08 mL) was added and stirring was continued at this temperature for an additional 45 min. The reaction mixture was poured in to 1M aqueous NH4Cl (30 mL), extracted with EtOAc (3×50 mL). The combined organics were washed with brine (2×30 mL), dried (Na2SO4), filtered and concentrated under reduced pressure. The residue was triturated with dichloromethane (8.0 mL); the precipitate was collected by filtration and washed with dichloromethane to afford the product as a light brown solid, (0.129 g, 71%). 1H-NMR (500 MHz, DMSO-d6) 6.72 (dd, J=0.5, 1.5 Hz, 1H), 7.33 (t, J=0.85 Hz, 1H), 8.00 (br s, 1H), 8.24 (br s, 1H), 8.51 (s, 1H), 11.87 (s, 1H), 13.09 (s, 1H).

Workup

  1. customthe microwave vial was placed in an oil-bath
  2. custompreheated at 100° C.
  3. stirringstirring
  4. waitwas continued at this temperature for an additional 45 min
  5. extractionextracted with EtOAc (3×50 mL)
  6. washThe combined organics were washed with brine (2×30 mL)
  7. dry with materialdried (Na2SO4)
  8. filtrationfiltered
  9. concentrationconcentrated under reduced pressure
  10. customThe residue was triturated with dichloromethane (8.0 mL)
  11. filtrationthe precipitate was collected by filtration
  12. washwashed with dichloromethane

Sources & evidence

ORD record
ord-3605ce2fe9624ce89fb6aee155d1d141
Source dataset
uspto-grants-2016_06
Patent number
US09371319B2

Reaction notes

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