HCID 11374420, compound → HCID 11175601, compound

HRID 2356248Notes

Reaction equation

HRID 2356248 reaction equation
[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:13]=[C:14]3[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH3:23])=[N:16][N:15]3[C:24]=2I)=[CH:8][CH:7]=1.[C:26]([Cu])#[N:27]>CN(C)C=O>[CH3:1][O:2][CH2:3][CH2:4][O:5][C:6]1[CH:11]=[CH:10][C:9]([C:12]2[N:13]=[C:14]3[CH:19]=[CH:18][C:17]([O:20][CH2:21][CH2:22][CH3:23])=[N:16][N:15]3[C:24]=2[C:26]#[N:27])=[CH:8][CH:7]=1

Participants

4

Reactant 2

HCID 11374420HCID 11374420, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 11175601HCID 11175601, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Procedure

A mixture of 2-[4-(2-methoxyethoxy)phenyl]-3-iodo-6-propoxyimidazo[1,2-b]pyridazine (100 mg, 0.22 mmol), cuprous cyanide (22 mg, 0.24 mmol) and N,N-dimethylformamide (2 mL) was heated at 80° for 22 hours. More CuCN (10 mg) was added and the mixture heated at 100° for 29 hours. Aqueous ferric chloride solution (5%, acidified with HCl) (7 mL) was added and the resulting mixture heated at 60° for 30 minutes. The resulting suspension was filtered and the collected solid washed with saturated, aqueous sodium bicarbonate solution, water (twice) and air-dried overnight. The beige coloured solid was radially chromatographed on silica gel. Elution with 0-1% methanol in dichloromethane provided Compound 110 (50 mg, 64%) as a brilliant white solid. 1H n.m.r. (CDCl3) δ 1.06, t, J=7.4 Hz, 3H; 1.76-1.96, m, 2H; 3.47, s, 3H; 3.74-3.82, m, 2H; 4.15-4.22, m, 2H; 4.37, t, J=6.6 Hz, 2H; 6.88, d, J=9.5 Hz, 1H; 7.04, d, J=8.8 Hz, 2H; 7.82, d, J=9.5 Hz, 1H; 8.09, d, J=8.7 Hz, 2H. Mass spectrum (APCI+) m/z 353 (M+H, 100%). Further elution afforded recovered starting material (21 mg, 21%).

Workup

  1. temperaturewas heated at 80° for 22 hours
  2. temperaturethe mixture heated at 100° for 29 hours
  3. temperaturethe resulting mixture heated at 60° for 30 minutes
  4. filtrationThe resulting suspension was filtered
  5. washthe collected solid washed with saturated, aqueous sodium bicarbonate solution, water (twice) and
  6. customair-dried overnight
  7. customwas radially chromatographed on silica gel
  8. washElution with 0-1% methanol in dichloromethane provided Compound 110 (50 mg, 64%) as a brilliant white solid
  9. washFurther elution
  10. customafforded
  11. customrecovered

Sources & evidence

ORD record
ord-f28bad3b4d2c48dc8184c4d056669e14
Source dataset
uspto-grants-2010_07
Patent number
US07759349B2

Reaction notes

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