Potassium Carbonate → N-(6-(1-oxoisoindolin-4-yl)naphthalen-2-yl)thiophene-3-carboxamide

HRID 908291Notes

Reaction equation

HRID 908291 reaction equation
Br[N:2]1[CH2:10][C:9]2[C:4](=[CH:5][CH:6]=[CH:7][CH:8]=2)[C:3]1=[O:11].CC1(C)C(C)(C)OB([C:20]2[CH:21]=[C:22]3[C:27](=[CH:28][CH:29]=2)[CH:26]=[C:25]([NH:30][C:31]([C:33]2[CH:37]=[CH:36][S:35][CH:34]=2)=[O:32])[CH:24]=[CH:23]3)O1.C([O-])([O-])=O.[K+].[K+].O1CCOCC1>[Pd].O>[O:11]=[C:3]1[C:4]2[C:9](=[C:8]([C:20]3[CH:21]=[C:22]4[C:27](=[CH:28][CH:29]=3)[CH:26]=[C:25]([NH:30][C:31]([C:33]3[CH:37]=[CH:36][S:35][CH:34]=3)=[O:32])[CH:24]=[CH:23]4)[CH:7]=[CH:6][CH:5]=2)[CH2:10][NH:2]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 67386422N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)thiophene-3-carboxamideHCID 86611253Bromoisoindolin-1-one

Product 1

HCID 16035434N-(6-(1-oxoisoindolin-4-yl)naphthalen-2-yl)thiophene-3-carboxamideYield 24%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 962WaterSolvent

Procedure

Bromoisoindolin-1-one (11.5 mg, 0.0542 mmol), N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)thiophene-3-carboxamide (43.3 mg, 0.114 mmol), Fibercat palladium catalyst (Johnson-Matthey, 21.0 mg), and K2CO3 (2 M in water, 0.1 ml, 0.2 mmol) were combined in a microwave reaction vessel and 1,4-dioxane (0.55 ml) was added. The reaction tube was sealed and heated in the microwave (CEM microwave) for 10 minutes at 50 Watts and 80 C. The reaction was cooled to room temperature, diluted with water (10 ml), and extracted with dichloromethane (6×5 ml). The organic extracts were combined, dried over sodium sulfate, filtered, and concentrated. The crude material was washed with 15:1 hexanes/EtOAc and then purified on HPLC (10%->95% MeCN/water with 0.1% TFA) to afford title compound (4.9 mg, 24%). MS (ESI pos. ion) m/z: 385 (M+H). Calc'd Exact Mass for C23H16N2O2S: 384.

Workup

  1. additionwas added
  2. customThe reaction tube was sealed
  3. temperatureheated in the microwave (CEM microwave) for 10 minutes at 50 Watts and 80 C
  4. extractionextracted with dichloromethane (6×5 ml)
  5. dry with materialdried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. washThe crude material was washed with 15:1 hexanes/EtOAc
  9. custompurified on HPLC (10%->95% MeCN/water with 0.1% TFA)

Sources & evidence

ORD record
ord-64dc3422c39642ae86a3a05a0dfac1d7
Source dataset
uspto-grants-2011_09
Patent number
US08017601B2

Reaction notes

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