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

HRID 908301Notes

Reaction equation

HRID 908301 reaction equation
Br[C:2]1[CH:10]=[C:9]2[C:5]([CH:6]=[CH:7][NH:8]2)=[CH:4][CH:3]=1.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:8]1[C:9]2[C:5](=[CH: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]=2)[CH:6]=[CH:7]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 6764936-BromoindoleHCID 67386422N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)thiophene-3-carboxamide

Product 1

HCID 58828851N-[6-(1H-Indol-6-yl)naphthalen-2-yl]thiophene-3-carboxamideYield 22%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 962WaterSolvent

Procedure

6-bromo-1H-indole (28.8 mg, 0.147 mmol), N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)thiophene-3-carboxamide (109.2 mg, 0.288 mmol), Fibercat palladium catalyst (Johnson-Matthey, 55.5 mg), and K2CO3 (2 M in water, 0.50 ml, 1.0 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 then 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 via HPLC (10%->95% MeCN/water with 0.1% TFA), silica gel (4:1->3:1->2:1->1:1 hexanes/EtOAc) to afford crude product. This crude material was then purified again via HPLC (same conditions as above) to afford title compound (11.9 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 for 20 minutes
  4. extractionextracted with EtOAc (10 ml; 2×5 ml)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. custompurified via HPLC (10%->95% MeCN/water with 0.1% TFA), silica gel (4:1->3:1->2:1->1:1 hexanes/EtOAc)
  9. customto afford crude product
  10. customThis crude material was then purified again via HPLC (same conditions as above)

Sources & evidence

ORD record
ord-d7f2bae109fe4dc98c6d9034ce7ccf0d
Source dataset
uspto-grants-2011_09
Patent number
US08017601B2

Reaction notes

Loading…