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

HRID 1614980Notes

Reaction equation

HRID 1614980 reaction equation
[C:1]([C:3]1[CH:8]=[CH:7][C:6]([NH:9][C:10](=[O:16])[O:11][C:12]([CH3:15])([CH3:14])[CH3:13])=[C:5](I)[CH:4]=1)#[N:2].C(N(CC)CC)C.[C:25]([C:27]1[CH:28]=[C:29]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:39])([CH3:38])[CH3:37])[CH:30]=[N:31][CH:32]=1)#[CH:26]>[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.O1CCCC1>[C:12]([O:11][C:10]([NH:9][C:6]1[CH:7]=[CH:8][C:3]([C:1]#[N:2])=[CH:4][C:5]=1[C:26]#[C:25][C:27]1[CH:28]=[C:29]([NH:33][C:34](=[O:40])[O:35][C:36]([CH3:38])([CH3:37])[CH3:39])[CH:30]=[N:31][CH:32]=1)=[O:16])([CH3:15])([CH3:14])[CH3:13]

Participants

7

Reactant 3

HCID 8471TriethylamineHCID 57962286Tert-butyl (5-ethynylpyridin-3-yl)carbamateHCID 58467859tert-Butyl (4-cyano-2-iodophenyl)carbamate

Product 1

HCID 58467911tert-Butyl [5-({2-[(tert-butoxycarbonyl)amino]-5-cyanophenyl}ethynyl)pyridin-3-yl]carbamateYield 52.8%

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418476HCID 178418476, compoundCatalystHCID 8028TetrahydrofuranSolvent

Procedure

Into a reaction flask were added tert-butyl (4-cyano-2-iodophenyl)carbamate (1.4 g, 4.1 mmol), copper(I) iodide (31 mg, 0.16 mmol), bis(triphenylphosphine)palladium(II) chloride (0.12 g, 0.16 mmol), tetrahydrofuran (10 mL), and triethylamine (0.63 mL, 4.5 mmol). The mixture was stirred under N2 bubbling for 5 minutes and tert-butyl (5-ethynylpyridin-3-yl)carbamate (0.90 g, 4.1 mmol) (prepared according to Example 17, Step B) was then added. The reaction mixture was stirred at 65° C. for 2 hours. The solvent was removed under vacuum and the residue was diluted with EtOAc and water. After separation, the organic layer was dried over Na2SO4 and concentrated under vacuum. The crude was purified by silica gel column chromatography to give the desired product (0.94 g, 52%). LCMS for C24H27N4O4 (M+H)+: m/z=435.2.

Workup

  1. stirringThe reaction mixture was stirred at 65° C. for 2 hours
  2. customThe solvent was removed under vacuum
  3. additionthe residue was diluted with EtOAc and water
  4. customAfter separation
  5. dry with materialthe organic layer was dried over Na2SO4
  6. concentrationconcentrated under vacuum
  7. customThe crude was purified by silica gel column chromatography

Sources & evidence

ORD record
ord-0d2f05e6d95943538d0847549bf6992a
Source dataset
uspto-grants-2014_07
Patent number
US08765727B2

Reaction notes

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