Dimethylformamide → N-[3-(5-{2-[3-pyridyl]ethenyl}fur-2-yl)-1-methyl-2-propynyl]-N-hydroxyurea

HRID 52171

Reaction equation

HRID 52171 reaction equation
I[C:2]1[O:3][C:4]([CH:7]=[CH:8][C:9]2[CH:10]=[N:11][CH:12]=[CH:13][CH:14]=2)=[CH:5][CH:6]=1.[OH:15][N:16]([CH:20]([C:22]#[CH:23])[CH3:21])[C:17]([NH2:19])=[O:18].CN(C)C=O.[NH4+].[OH-]>C(NCC)C.CC#N.CC#N.Cl[Pd]Cl.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[N:11]1[CH:12]=[CH:13][CH:14]=[C:9]([CH:8]=[CH:7][C:4]2[O:3][C:2]([C:23]#[C:22][CH:20]([N:16]([OH:15])[C:17]([NH2:19])=[O:18])[CH3:21])=[CH:6][CH:5]=2)[CH:10]=1

Participants

8

Reactant 4

HCID 6228DimethylformamideHCID 14923Ammonium HydroxideHCID 19963264N-hydroxy-N-(butyn-2-yl)ureaHCID 545240982-Iodo-5-[2-{3-pyridyl}ethenyl]furan

Product 1

HCID 53636693N-[3-(5-{2-[3-pyridyl]ethenyl}fur-2-yl)-1-methyl-2-propynyl]-N-hydroxyureaYield 37.9%

Reagents, catalysts & solvents 3

HCID 11776TriphenylphosphineCatalystHCID 6093782Bis(acetonitrile)dichloropalladiumCatalystHCID 8021DiethylamineSolvent

Procedure

To a stirred solution of 2-iodo-5-[2-{3-pyridyl}ethenyl]furan (1.4 g, 4.7 mmol), prepared as in step 5, and N-hydroxy-N-(butyn-2-yl)urea (0.64 g, 5 mmol), prepared as in step 2, in diethylamine (10 mL) was added dimethylformamide (1 mL), triphenylphosphine (0.026 g, 0.1 mmol), cuprous iodide (5 mg, 25 mmol) and bis(acetonitrile)palladium(II) chloride (13 mg, 50 mmol). The mixture was stirred overnight at ambient temperature. Aqueous NH4OH was added and the mixture extracted thoroughly with CH2Cl2. The combined organic layer was washed with brine, dried (MgSO4) and evaporated under reduced pressure. The resulting residue was purified by column chromatography on silica gel eluting with 5% MeOH--CH2Cl2 to afford an off-white solid. Recrystallization from ethyl acetate-hexanes gave 530 mg of the title compound. m.p. 166° C. 1H NMR (DMSO-d6, 300 MHz) δ1.38 (d, J=7 Hz, 3H), 5.19 (q, J=7 Hz, 1H), 6.61 (bs, 2H), 6.82 (d, J=3 Hz, 1H), 6.82 (d, J=3 Hz, 1H), 7.09 (d, J=16 Hz, 1H), 7.25 (d, J=16 Hz, 1H), 7.39 (m, 1H), 7.77 (m, 1H), 8.03 (m, 1H), 8.45 (m, 1H), 8.77 (m, 1H), 9.43 (s, 1H). MS (DCI/NH3) m/e 298 (M+H)+. Anal calcd for C16H15N3O3 : C, 64.63; H, 5.08; N, 14.13. Found: C, 64.01; H, 5.09; N, 14.06.

Workup

  1. extractionthe mixture extracted thoroughly with CH2Cl2
  2. washThe combined organic layer was washed with brine
  3. dry with materialdried (MgSO4)
  4. customevaporated under reduced pressure
  5. customThe resulting residue was purified by column chromatography on silica gel eluting with 5% MeOH
  6. customCH2Cl2 to afford an off-white solid
  7. customRecrystallization from ethyl acetate-hexanes

Sources & evidence

ORD record
ord-4b0f31714e074fc6b058cad5f5fa22a2
Source dataset
uspto-grants-1997_04
Patent number
US05616596

Linked notes

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