Imidazole → HCID 18361736, compound

HRID 382925Notes

Reaction equation

HRID 382925 reaction equation
[NH:1]1[CH:5]=[CH:4][N:3]=[CH:2]1.[H-].[Na+].Br[C:9]1[N:14]=[C:13]([CH2:15][O:16][CH:17]2[CH2:22][CH2:21][CH2:20][CH2:19][O:18]2)[CH:12]=[CH:11][CH:10]=1>CN(C)C=O>[N:1]1([C:9]2[N:14]=[C:13]([CH2:15][O:16][CH:17]3[CH2:22][CH2:21][CH2:20][CH2:19][O:18]3)[CH:12]=[CH:11][CH:10]=2)[CH:5]=[CH:4][N:3]=[CH:2]1

Participants

5

Reactant 3

HCID 795ImidazoleHCID 24758Sodium hydrideHCID 11119203HCID 11119203, compound

Product 1

HCID 18361736HCID 18361736, compoundYield 73%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent2×

Conditions

Temperature
80 °C

Procedure

Imidazole (500 mg, 74 mmol) was added to a stirred mixture of sodium hydride (300 mg of a 60% dispersion in oil, 75 mmol) and dimethylformamide (20 ml), at room temperature under nitrogen. After 0.75 h, 6-bromo-2-[(tetrahydropyran-2-yl)oxymethyl]pyridine (400 mg 14.6 mmol) prepared following the procedure given for Example 11 part a in dimethylformamide (5 ml) was added. The mixture was heated at 80° C. for 24 h then in a sealed tube at 120° C. for 4 h. The solvent was evaporated in vacuo and the residue partitioned between water and ethyl acetate. The aqueous phase was separated and extracted with ethyl acetate (×3). The combined extracts were dried (MgSO4), and evaporated in vacuo and the residue flash chromatographed on silica gel, eluting with 5% methanol/dichloromethane to give the title-compound (280 mg, 73%), 1H NMR (250 MHz, CDCl3), δ 1.5-1.8 (6H, m, 3 of CH2), 3.58 (1H, m, CH2O), 3.93 (1H, m, CH2O), 4.66 (1H, d, J=14.1 Hz, CH2O), 4.82 (1H, d, CH), 4.90 (1H, d, J=14.1 Hz, CH2O), 7.19 (1H, br s, Ar—H), 7.24 (1H, d, J=8.2 Hz, Ar—H), 7.43 (1H, dd, J=7.6 Hz and 7.1 Hz, Ar—H), 7.64 (H, t, J=1.2 Hz, Ar—H), 7.83 (1H, t, J=7.9 Hz, Ar—H), 8.35 (1H, s, Ar—H); MS (ES+) m/e 260 [MH]+.

Workup

  1. customat room temperature
  2. additionwas added
  3. waitin a sealed tube at 120° C. for 4 h
  4. customThe solvent was evaporated in vacuo
  5. customthe residue partitioned between water and ethyl acetate
  6. customThe aqueous phase was separated
  7. extractionextracted with ethyl acetate (×3)
  8. dry with materialThe combined extracts were dried (MgSO4)
  9. customevaporated in vacuo
  10. customthe residue flash chromatographed on silica gel
  11. washeluting with 5% methanol/dichloromethane

Sources & evidence

ORD record
ord-467e7bb994ea4e48a206ca5f3cf5ffb1
Source dataset
uspto-grants-2001_10
Patent number
US06310203B1

Reaction notes

Loading…