Triethylamine → N-(4-(7-((2-tert-butoxypyridin-4-yl)ethynyl)-4-oxo-4H-chromen-3-yl)phenyl)methanesulfonamide

HRID 1188262Notes

Reaction equation

HRID 1188262 reaction equation
[C:1]([C:3]1[CH:12]=[C:11]2[C:6]([C:7](=[O:24])[C:8]([C:13]3[CH:18]=[CH:17][C:16]([NH:19][S:20]([CH3:23])(=[O:22])=[O:21])=[CH:15][CH:14]=3)=[CH:9][O:10]2)=[CH:5][CH:4]=1)#[CH:2].Br[C:26]1[CH:31]=[CH:30][N:29]=[C:28]([O:32][C:33]([CH3:36])([CH3:35])[CH3:34])[CH:27]=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(N(CC)CC)C>O1CCCC1.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.[Cu](I)I>[C:33]([O:32][C:28]1[CH:27]=[C:26]([C:2]#[C:1][C:3]2[CH:12]=[C:11]3[C:6]([C:7](=[O:24])[C:8]([C:13]4[CH:18]=[CH:17][C:16]([NH:19][S:20]([CH3:23])(=[O:22])=[O:21])=[CH:15][CH:14]=4)=[CH:9][O:10]3)=[CH:5][CH:4]=2)[CH:31]=[CH:30][N:29]=1)([CH3:36])([CH3:34])[CH3:35]

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 11776TriphenylphosphineHCID 457878724-Bromo-2-tert-butoxypyridineHCID 86695056N-(4-(7-ethynyl-4-oxo-4H-chromen-3-yl)phenyl)methanesulfonamide

Product 1

HCID 86695057N-(4-(7-((2-tert-butoxypyridin-4-yl)ethynyl)-4-oxo-4H-chromen-3-yl)phenyl)methanesulfonamide

Reagents, catalysts & solvents 3

HCID 83717Copper iodideCatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Conditions

Temperature
85 °C

Procedure

N-(4-(7-ethynyl-4-oxo-4H-chromen-3-yl)phenyl)methanesulfonamide (100 mg, 0.29 mmol) was combined with 4-bromo-2-tert-butoxypyridine (0.074 mg, 1.1 eq), PdCl2(PPh3)2 (10 mg, 0.05 eq), copper iodide (4 mg 0.002 eq), triphenylphosphine (6 mg 0.03 eq) and triethylamine (0.12 ml, 4.0 eq) in dry tetrahydrofuran (10 ml) and heated in microwave for 30 minutes at 85° C. Solvent was removed from the product under reduced pressure, and the residue was extracted with ethyl acetate in the presence of water. The organic phase was dried over magnesium sulfate, filtered and concentrated under reduced pressure to afford N-(4-(7-((2-tert-butoxypyridin-4-yl)ethynyl)-4-oxo-4H-chromen-3-yl)phenyl)methanesulfonamide. This crude product was dissolved in dichloromethane/trifluoroacetic acid 1:1 (4 ml) and stirred at room temperature for 1 hour. The solvent was removed under reduced pressure, and the residue was extracted with ethyl acetate in the presence of water. The organic phase was dried over magnesium sulfate, filtered and concentrated under reduced pressure. The product was heated in acetonitrile, cooled, and the solids were filtered out. This procedure was repeated twice in order to afford N-(4-(4-oxo-7-((2-oxo-1,2-dihydropyridin-4-yl)ethynyl)-4H-chromen-3-yl)phenyl)methanesulfonamide.

Workup

  1. customSolvent was removed from the product under reduced pressure
  2. extractionthe residue was extracted with ethyl acetate in the presence of water
  3. dry with materialThe organic phase was dried over magnesium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated under reduced pressure

Sources & evidence

ORD record
ord-c9fdb1569ef44975bd1c3b12bfbbb046
Source dataset
uspto-grants-2014_03
Patent number
US08673966B2

Reaction notes

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