Potassium Carbonate → N-[6-(1H-Indol-4-yl)naphthalen-2-yl]thiophene-3-carboxamide

HRID 908299Notes

Reaction equation

HRID 908299 reaction equation
Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[CH:5][NH:6]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+].O1CCOCC1>[Pd].O>[NH:6]1[C:7]2[C: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][CH:8]=2)[CH:4]=[CH:5]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 6764944-BromoindoleHCID 67386422N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)thiophene-3-carboxamide

Product 1

HCID 58828872N-[6-(1H-Indol-4-yl)naphthalen-2-yl]thiophene-3-carboxamideYield 22%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 962WaterSolvent

Procedure

4-bromo-1H-indole (31.0 mg, 0.158 mmol), N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)thiophene-3-carboxamide (114.5 mg, 0.302 mmol), Fibercat palladium catalyst (Johnson-Matthey, 34.5 mg), and K2CO3 (2 M in water, 0.45 ml, 0.90 mmol) were combined in a microwave reaction vessel and 1,4-dioxane (1.5 ml) was added. The reaction tube was sealed and heated in the microwave (CEM microwave) at 60 Watts and 80 C, first for 10 minutes, and then for 20 minutes. The reaction was cooled to room temperature, diluted with water (5 ml), and extracted with EtOAc (10 ml, 2×5 ml). The organic extracts were combined, dried over sodium sulfate, filtered, concentrated, and purified on HPLC (10%->95% MeCN/water with 0.1% TFA). The fractions with product were purified on silica gel (3:1->1:1 hexanes/EtOAc) to afford title compound (12.8 mg, 22%). MS (ESI pos. ion) m/z: 369 (M+H). Calc'd Exact Mass for C23H16N2OS: 368.

Workup

  1. additionwas added
  2. customThe reaction tube was sealed
  3. temperatureheated in the microwave (CEM microwave) at 60 Watts and 80 C, first for 10 minutes
  4. extractionextracted with EtOAc (10 ml, 2×5 ml)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified on HPLC (10%->95% MeCN/water with 0.1% TFA)
  9. customThe fractions with product were purified on silica gel (3:1->1:1 hexanes/EtOAc)

Sources & evidence

ORD record
ord-6517008f79404a2c8f7057d87ba81704
Source dataset
uspto-grants-2011_09
Patent number
US08017601B2

Reaction notes

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