Sodium Carbonate → N-(6-(1H-indazol-5-yl)naphthalen-2-yl)thiophene-3-carboxamide

HRID 908319Notes

Reaction equation

HRID 908319 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][N:6]=[CH:5]2.CC1(C)C(C)(C)OB([C:19]2[CH:20]=[C:21]3[C:26](=[CH:27][CH:28]=2)[CH:25]=[C:24]([NH:29][C:30]([C:32]2[CH:36]=[CH:35][S:34][CH:33]=2)=[O:31])[CH:23]=[CH:22]3)O1.C([O-])([O-])=O.[K+].[K+].C([O-])([O-])=O.[Na+].[Na+]>[Pd].O.C(Cl)Cl.O1CCOCC1>[NH:7]1[C:8]2[C:4](=[CH:3][C:2]([C:19]3[CH:20]=[C:21]4[C:26](=[CH:27][CH:28]=3)[CH:25]=[C:24]([NH:29][C:30]([C:32]3[CH:36]=[CH:35][S:34][CH:33]=3)=[O:31])[CH:23]=[CH:22]4)=[CH:10][CH:9]=2)[CH:5]=[N:6]1

Participants

9

Reactant 4

HCID 10340Sodium CarbonateHCID 11430Potassium CarbonateHCID 7619295-bromo-1H-indazoleHCID 67386422N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)thiophene-3-carboxamide

Product 1

HCID 58828843N-(6-(1H-indazol-5-yl)naphthalen-2-yl)thiophene-3-carboxamideYield 44%

Reagents, catalysts & solvents 4

HCID 23938PalladiumCatalyst2×HCID 962WaterSolventHCID 6344DichloromethaneSolventHCID 312751,4-DioxaneSolvent

Procedure

5-bromo-1H-indazole (21 mg, 0.087 mmol), N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)thiophene-3-carboxamide (50 mg, 0.13 mmol), Fibercat palladium catalyst (Johnson-Matthey, 2.5 mg), and K2CO3 (2 M in water, 0.25 ml, 0.5 mmol) were combined in a microwave reaction vessel and 1,4-dioxane (2 ml) was added. The reaction tube was sealed and heated in the microwave (CEM microwave) at 50 Watts and 80 C for 10 minutes. The reaction was then cooled to room temperature, and more Fibercat palladium catalyst (8 mg) was added, along with 2 M Na2CO3 (0.25 ml). The reaction was heated in the microwave at 100 C and 75 Watts for 10 minutes, and then re-cooled to room temperature. The reaction was then diluted with water and methylene chloride, and the organic layer was separated, dried over sodium sulfate, filtered, concentrated, and treated with methylene chloride to afford a precipitate. This suspension was filtered, and the solid was collected to afford the title compound (14 mg, 44%). MS (ESI pos. ion) m/z: 370 (M+H). Calc'd Exact Mass for C22H15N3OS: 369.

Workup

  1. additionwas added
  2. customThe reaction tube was sealed
  3. temperatureheated in the microwave (CEM microwave) at 50 Watts and 80 C for 10 minutes
  4. temperatureThe reaction was heated in the microwave at 100 C and 75 Watts for 10 minutes
  5. temperaturere-cooled to room temperature
  6. customthe organic layer was separated
  7. dry with materialdried over sodium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated
  10. additiontreated with methylene chloride
  11. customto afford a precipitate
  12. filtrationThis suspension was filtered
  13. customthe solid was collected

Sources & evidence

ORD record
ord-8a793dbde8c7402285c0b59bf3ab0950
Source dataset
uspto-grants-2011_09
Patent number
US08017601B2

Reaction notes

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