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

HRID 908304Notes

Reaction equation

HRID 908304 reaction equation
Br[C:2]1[CH:10]=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[N: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]=[N:5]1

Participants

7

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 223525484-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 58828894N-[6-(1H-Indazol-4-yl)naphthalen-2-yl]thiophene-3-carboxamideYield 10.4%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 962WaterSolvent

Procedure

4-bromo-1H-indazole (37.9 mg, 0.192 mmol), N-(6-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)naphthalen-2-yl)thiophene-3-carboxamide (145.7 mg, 0.384 mmol), Fibercat palladium catalyst (Johnson-Matthey, 64.7 mg), and K2CO3 (2 M in water, 0.75 ml, 1.5 mmol) were combined in a microwave reaction vessel and 1,4-dioxane (2.3 ml) was added. The reaction tube was sealed and heated in the microwave (CEM microwave) at 60 Watts and 85 C for 20 minutes. The reaction was then cooled to room temperature, diluted with water (5 ml), and extracted with EtOAc (3×10 ml). The organic extracts were combined, washed with water (3×5 ml), dried over sodium sulfate, filtered, concentrated, and purified via silica gel (Biotage instrument, 13%->75% EtOAc/hexanes). This crude material was then purified via HPLC (10%->95% MeCN/water with 0.1% TFA) to afford title compound (7.4 mg, 10%). 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 60 Watts and 85 C for 20 minutes
  4. extractionextracted with EtOAc (3×10 ml)
  5. washwashed with water (3×5 ml)
  6. dry with materialdried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. custompurified via silica gel (Biotage instrument, 13%->75% EtOAc/hexanes)
  10. customThis crude material was then purified via HPLC (10%->95% MeCN/water with 0.1% TFA)

Sources & evidence

ORD record
ord-2c3b81514c1d48ec8ed49b5c737c96b2
Source dataset
uspto-grants-2011_09
Patent number
US08017601B2

Reaction notes

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