Tetrahydrofuran → tert-Butyl [5-({2-[(tert-butoxycarbonyl)amino]-5-nitrophenyl}ethynyl)pyridin-3-yl]carbamate

HRID 541885Notes

Reaction equation

HRID 541885 reaction equation
I[C:2]1[CH:7]=[C:6]([N+:8]([O-:10])=[O:9])[CH:5]=[CH:4][C:3]=1[NH:11][C:12](=[O:18])[O:13][C:14]([CH3:17])([CH3:16])[CH3:15].O1CCCC1.[C:24]([C:26]1[CH:27]=[C:28]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:38])([CH3:37])[CH3:36])[CH:29]=[N:30][CH:31]=1)#[CH:25]>[Cu]I.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.C(N(CC)CC)C>[C:14]([O:13][C:12]([NH:11][C:3]1[CH:4]=[CH:5][C:6]([N+:8]([O-:10])=[O:9])=[CH:7][C:2]=1[C:25]#[C:24][C:26]1[CH:27]=[C:28]([NH:32][C:33](=[O:39])[O:34][C:35]([CH3:37])([CH3:36])[CH3:38])[CH:29]=[N:30][CH:31]=1)=[O:18])([CH3:17])([CH3:16])[CH3:15]

Participants

7

Reactant 3

HCID 8028TetrahydrofuranHCID 7098713Tert-butyl 4-nitro-2-iodophenylcarbamateHCID 57962286Tert-butyl (5-ethynylpyridin-3-yl)carbamate

Product 1

HCID 57961805tert-Butyl [5-({2-[(tert-butoxycarbonyl)amino]-5-nitrophenyl}ethynyl)pyridin-3-yl]carbamateYield 85.9%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8471TriethylamineSolvent

Procedure

Into the reaction flask was added tert-butyl (2-iodo-4-nitrophenyl)carbamate (1.5 g, 4.1 mmol) and copper(I) iodide (0.031 g, 0.16 mmol), bis(triphenylphosphine)palladium(II) chloride (0.12 g, 0.16 mmol), tetrahydrofuran (10 mL), and triethylamine (0.63 mL). The mixture was stirred under bubbling N2 for 5 min, and tert-butyl (5-ethynylpyridin-3-yl)carbamate (0.90 g, 4.1 mmol) was then added. The reaction mixture was stirred at 65° C. for 1 h. After concentration, the residue was diluted with EtOAc and water. The aqueous layer was extracted again with EtOAc. The organic layers were combined and dried over Na2SO4. After filtration and concentration, the crude was purified by silica gel column chromatography to give the desired product (1.6 g, 85%). LCMS for C23H27N4O6 (M+H)+: m/z=455.1.

Workup

  1. stirringThe reaction mixture was stirred at 65° C. for 1 h
  2. concentrationAfter concentration
  3. additionthe residue was diluted with EtOAc and water
  4. extractionThe aqueous layer was extracted again with EtOAc
  5. dry with materialdried over Na2SO4
  6. filtrationAfter filtration and concentration
  7. customthe crude was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-35cd0205c64f46ebb284da88f40a808b
Source dataset
uspto-grants-2014_10
Patent number
US08871753B2

Reaction notes

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