Imidazole → HCID 68537745, compound

HRID 2266991Notes

Reaction equation

HRID 2266991 reaction equation
C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.N1C=CN=C1.[I:25]I.O[CH2:28][C:29]1[CH:30]=[C:31]([CH:41]=[CH:42][CH:43]=1)[O:32][C:33]1[CH:34]=[C:35]([CH:38]=[CH:39][N:40]=1)[C:36]#[N:37]>ClCCl.C(OCC)(=O)C>[I:25][CH2:28][C:29]1[CH:30]=[C:31]([CH:41]=[CH:42][CH:43]=1)[O:32][C:33]1[CH:34]=[C:35]([CH:38]=[CH:39][N:40]=1)[C:36]#[N:37]

Participants

7

Reactant 4

HCID 795ImidazoleHCID 807IodineHCID 11776TriphenylphosphineHCID 59599460HCID 59599460, compound

Product 1

HCID 68537745HCID 68537745, compoundYield 55.9%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 8857Ethyl AcetateSolvent

Procedure

Mix polymer-supported triphenylphosphine (2.33 mmol/g load capacity, 0.85 g, 1.99 mmol), imidazole (0.14 g, 1.99 mmol) and iodine (0.51 g, 1.99 mmol) in dichloromethane (8 mL) in a vial (0.75 oz). Seal and shake for 10 minutes. Add a solution of 2-(3-hydroxymethyl-phenoxy)-isonicotinonitrile (0.30 g, 1.33 mmol) in dichloromethane (3 mL) and shake for 2 hrs. Filter the resin and wash with dichloromethane (50 mL). Concentrate the filtrate under reduced pressure to give a residue. Dissolve the residue in ethyl acetate (25 mL), wash with saturated sodium thiosulfate solution (2×25 mL) and dry over sodium sulfate. Filter and concentrate to give 2-(3-iodomethyl-phenoxy)-isonicotinonitrile as a yellow solid (0.25 g, 53%). Mix the yellow solid (0.25 g, 0.70 mmol), 1-(2,4-dihydroxy-3-methyl-phenyl)-propan-1-one (0.14 g, 0.77 mmol) and cesium carbonate (0.25 g, 0.77 mmol) in acetone (7 mL). Heat to 50° C. for 2.5 hrs. Allow the reaction to cool to ambient temperature and concentrate under reduced pressure to give a solid. Dilute with ethyl acetate (25 mL) and filter. Concentrate the filtrate under reduced pressure to give an oil. Triturate with methanol (50 mL) and filter to give a solid. Purification by flash chromatography using 5% ethyl acetate/hexanes to 20% ethyl acetate/hexanes as gradient eluent yields the title compound (0.16 g, 60%): MS (m/z): 387.2 (M−1). 1H NMR (CDCl3) 12.91 (s, 1H), 8.34 (d, J=5.1 Hz, 1H), 7.65 (d, J=9.0 Hz, 1H), 7.50 (t, J=8.0 Hz, 1H), 7.36 (d, J=7.8 Hz, 1H), 7.31-7.24 (m, 2H), 7.21 (s, 1H), 7.15 (d, J=8.0 Hz, 1H), 6.51 (d, J=9.0 Hz, 1H), 5.23 (s, 2H), 3.00 (q, J=7.5 Hz, 2H), 2.19 (s, 3H), 1.26 (t, J=7.5 Hz, 3H).

Workup

  1. customSeal
  2. waitshake for 2 hrs
  3. filtrationFilter the resin
  4. washwash with dichloromethane (50 mL)
  5. concentrationConcentrate the filtrate under reduced pressure
  6. customto give a residue
  7. washwash with saturated sodium thiosulfate solution (2×25 mL)
  8. dry with materialdry over sodium sulfate
  9. filtrationFilter
  10. concentrationconcentrate

Sources & evidence

ORD record
ord-805724f5e03640428512d961f8f19f0e
Source dataset
uspto-grants-2010_12
Patent number
US07858646B2

Reaction notes

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