Triethylamine → tert-Butyl 4-(6-bromo-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazole-1-carboxylate

HRID 2205855Notes

Reaction equation

HRID 2205855 reaction equation
[Br:1][C:2]1[CH:7]=[C:6]([NH:8][S:9]([CH3:12])(=[O:11])=[O:10])[C:5](I)=[CH:4][N:3]=1.[C:14]([C:16]1[CH:17]=[N:18][N:19]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH:20]=1)#[CH:15].C(N(CC)CC)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.CN(C=O)C>[Br:1][C:2]1[N:3]=[CH:4][C:5]2[CH:15]=[C:14]([C:16]3[CH:17]=[N:18][N:19]([C:21]([O:23][C:24]([CH3:27])([CH3:26])[CH3:25])=[O:22])[CH:20]=3)[N:8]([S:9]([CH3:12])(=[O:11])=[O:10])[C:6]=2[CH:7]=1

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 45382264tert-butyl 4-ethynyl-1H-pyrazole-1-carboxylateHCID 86706267N-(2-Bromo-5-iodopyridin-4-yl)methanesulfonamide

Product 1

HCID 86706269tert-Butyl 4-(6-bromo-1-(methylsulfonyl)-1H-pyrrolo[3,2-c]pyridin-2-yl)-1H-pyrazole-1-carboxylate

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

To a mixture of N-(2-bromo-5-iodopyridin-4-yl)methanesulfonamide (8) (419 mg, 1.11 mmol) and tert-butyl 4-ethynyl-1H-pyrazole-1-carboxylate (4) (277 mg, 1.44 mmol, 1.3 equiv) was added copper(I) iodide (7.4 mg 0.039 mmole) and DMF (4 mL), followed by triethylamine (0.69 mL, 497 mg, 4.92 mmol). The reaction was flushed twice with nitrogen. Bis(triphenylphosphine)palladium chloride (27 mg, 0.038 mmole) was added and the reaction flushed twice more with nitrogen, it was heated at 60° C. for 70 minutes. The reaction was added to water (40 mL) and extracted with ethyl acetate (3×20 mL). The combined extracts were washed with water (3×20 mL) and with brine, dried and evaporated. The residue was purified on four 2 mm 20×20 cm silica prep tlc plates, eluted with 3:1 ethyl acetate:cyclohexane. The product band was recovered with acetone giving the title compound (251 mg, 51%). 1H-NMR (CDCl3, 500 MHz): δ 1.73 (s, 9H), 3.02 (s, 3H), 6.81 (s, 1H), 7.97 (s, 1H), 8.26 (s, 1H), 8.43 (s, 1H), 8.69 (s, 1H).

Workup

  1. customThe reaction was flushed twice with nitrogen
  2. customthe reaction flushed twice more with nitrogen, it
  3. additionThe reaction was added to water (40 mL)
  4. extractionextracted with ethyl acetate (3×20 mL)
  5. washThe combined extracts were washed with water (3×20 mL) and with brine
  6. customdried
  7. customevaporated
  8. customThe residue was purified on four 2 mm 20×20 cm silica prep tlc plates
  9. washeluted with 3:1 ethyl acetate
  10. customThe product band was recovered with acetone giving the title compound (251 mg, 51%)

Sources & evidence

ORD record
ord-26e9f8686b824fa6bfdef7eefdf872b9
Source dataset
uspto-grants-2016_06
Patent number
US09371319B2

Reaction notes

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