Triethylamine → (S)-5-[(6-hydroxypyridin-3-yl)ethynyl]-N-[methyl(oxo)phenyl-lambda6-sulfanylidene]nicotinamide

HRID 391532Notes

Reaction equation

HRID 391532 reaction equation
[CH3:1][S@:2](=[O:24])([C:18]1[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=1)=[N:3][C:4](=[O:17])[C:5]1[CH:10]=[C:9]([C:11]#[C:12][Si](C)(C)C)[CH:8]=[N:7][CH:6]=1.[OH:25][C:26]1[CH:31]=[CH:30][C:29](I)=[CH:28][N:27]=1.C(N(CC)CC)C.[F-].C([N+](CCCC)(CCCC)CCCC)CCC>CN(C=O)C.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[OH:25][C:26]1[N:27]=[CH:28][C:29]([C:12]#[C:11][C:9]2[CH:8]=[N:7][CH:6]=[C:5]([CH:10]=2)[C:4]([N:3]=[S@@:2]([CH3:1])(=[O:24])[C:18]2[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=2)=[O:17])=[CH:30][CH:31]=1

Participants

8

Reactant 4

HCID 8471TriethylamineHCID 4595002-Hydroxy-5-iodopyridineHCID 2724141Tetrabutylammonium FluorideHCID 24953135(S)-N-[methyl(oxo)phenyl-lambda6-sulfanylidene]-5-[(trimethylsilyl)ethynyl]nicotinamide

Product 1

HCID 178504646(S)-5-[(6-hydroxypyridin-3-yl)ethynyl]-N-[methyl(oxo)phenyl-lambda6-sulfanylidene]nicotinamideYield 6.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
85 °C

Procedure

A solution of (S)—N-[methyl(oxo)phenyl-λ6-sulfanylidene]-5-[(trimethylsilyl)ethynyl]-nicotinamide (150 mg, 0.42 mmol) and 2-hydroxy-5-iodopyridine (105.4 mg, 0.46 mmol) in DMF (2.1 mL) was degassed (vacuum and argon). The resulting solution was treated tetrakis(triphenylphosphine)palladium(0) (24 mg, 0.021 mmol), triethylamine (0.08 mL, 0.55 mmol), and CuI (8 mg, 0.042 mmol). The reaction mixture was then heated to 85° C. and tetrabutylammonium fluoride (1.0 M solution in THF, 0.46 mL, 0.46 mmol) was added dropwise over 10 min. The reaction was allowed to be stirred at 85° C. for 2 hours. The reaction mixture was partitioned between EtOAc and H2O. The organic extracts and associated solid were collected and concentrated. The residue was purified by chromatography (silica gel, gradient elution MeOH—CHCl3: 1:100-1:4). The product containing fractions were collected, concentrated, and the brown solid residue was triturated with a combination of MeOH and EtOAc. The resulting mixture was filtered and the filtrate allowed to stand at room temperature. The solid which precipitated from solution was collected and dried to give the title compound as a white solid (11 mg).

Workup

  1. customThe reaction mixture was partitioned between EtOAc and H2O
  2. customwere collected
  3. concentrationconcentrated
  4. customThe residue was purified by chromatography (silica gel, gradient elution MeOH—CHCl3: 1:100-1:4)
  5. additionThe product containing fractions
  6. customwere collected
  7. concentrationconcentrated
  8. customthe brown solid residue was triturated with a combination of MeOH and EtOAc
  9. filtrationThe resulting mixture was filtered
  10. customto stand at room temperature
  11. customThe solid which precipitated from solution
  12. customwas collected
  13. customdried

Sources & evidence

ORD record
ord-d4edbbd2a0594c57b91d6b1263f9b95d
Source dataset
uspto-grants-2013_02
Patent number
US08383825B2

Reaction notes

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