Potassium Carbonate → N-[6-(1H-Indol-5-yl)naphthalen-2-yl]thiophene-3-carboxamide

HRID 908300Notes

Reaction equation

HRID 908300 reaction equation
Br[C:2]1[CH:3]=[C:4]2[C:8](=[CH:9][CH:10]=1)[NH:7][CH: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+].O1CCOCC1>[Pd].O>[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]=[CH:6]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 249055-BromoindoleHCID 312751,4-DioxaneHCID 67386422N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)thiophene-3-carboxamide

Product 1

HCID 58828860N-[6-(1H-Indol-5-yl)naphthalen-2-yl]thiophene-3-carboxamideYield 21%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 962WaterSolvent

Procedure

5-bromo-1H-indole (31.4 mg, 0.160 mmol), N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)thiophene-3-carboxamide (114 mg, 0.301 mmol), Fibercat palladium catalyst (Johnson-Matthey, 31 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 for 20 minutes. The reaction was cooled to room temperature, diluted with water (5 ml), and extracted with EtOAc (3×10 ml). The organic extracts were combined, dried over sodium sulfate, filtered, concentrated, and purified on silica gel (5:1->4:1->2:1 hexanes/EtOAc) to afford crude product. This crude material was then purified two times via HPLC (10%->95% MeCN/water with 0.1% TFA) afford title compound (12.2 mg, 21%). 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 for 20 minutes
  4. extractionextracted with EtOAc (3×10 ml)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified on silica gel (5:1->4:1->2:1 hexanes/EtOAc)
  9. customto afford crude product
  10. customThis crude material was then purified two times via HPLC (10%->95% MeCN/water with 0.1% TFA)

Sources & evidence

ORD record
ord-c986e6e4b9b149af994f51f451873ebe
Source dataset
uspto-grants-2011_09
Patent number
US08017601B2

Reaction notes

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