Phosphorus oxychloride → 2-chloro-7-(3,5-dimethyl-4-isoxazolyl)-8-(methyloxy)-1-[(1R)-1-phenylethyl]-1H-imidazo[4,5-c]quinoline

HRID 81981Notes

Reaction equation

HRID 81981 reaction equation
[CH3:1][C:2]1[C:6]([C:7]2[C:8]([O:29][CH3:30])=[CH:9][C:10]3[C:11]4[N:19]([C@@H:20]([C:22]5[CH:27]=[CH:26][CH:25]=[CH:24][CH:23]=5)[CH3:21])[C:18](=O)[NH:17][C:12]=4[CH:13]=[N:14][C:15]=3[CH:16]=2)=[C:5]([CH3:31])[O:4][N:3]=1.O=P(Cl)(Cl)[Cl:34].P(Cl)(Cl)(Cl)(Cl)Cl>>[Cl:34][C:18]1[N:19]([C@@H:20]([C:22]2[CH:23]=[CH:24][CH:25]=[CH:26][CH:27]=2)[CH3:21])[C:11]2[C:10]3[CH:9]=[C:8]([O:29][CH3:30])[C:7]([C:6]4[C:2]([CH3:1])=[N:3][O:4][C:5]=4[CH3:31])=[CH:16][C:15]=3[N:14]=[CH:13][C:12]=2[N:17]=1

Participants

4

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 24819Phosphorus pentachlorideHCID 529351837-(3,5-Dimethyl-4-isoxazolyl)-8-(methyloxy)-1-[(1R)-1-phenylethyl]-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one

Product 1

HCID 709804382-chloro-7-(3,5-dimethyl-4-isoxazolyl)-8-(methyloxy)-1-[(1R)-1-phenylethyl]-1H-imidazo[4,5-c]quinolineYield 8.99%

Procedure

7-(3,5-Dimethyl-4-isoxazolyl)-8-(methyloxy)-1-[(1R)-1-phenylethyl]-1,3-dihydro-2H-imidazo[4,5-c]quinolin-2-one (for a preparation see Intermediate 11) (0.33 g, 0.796 mmol) was heated in a mixture of POCl3 (1 ml, 10.73 mmol) and PCl5 (0.166 g, 0.796 mmol) at 120° C. for 5 h, then cooled and allowed to stand at room temperature overnight. The mixture was evaporated in vacuo and then the residue suspended in toluene and evaporated to a brown gum. This was dissolved in DCM (20 ml) and washed with saturated sodium hydrogen carbonate solution, then the organic layer was loaded onto a 25 g silica cartridge. The column was eluted with EtOAc/cyclohexane (0-100%) and the product-containing fractions evaporated in vacuo to give 2-chloro-7-(3,5-dimethyl-4-isoxazolyl)-8-(methyloxy)-1-[(1R)-1-phenylethyl]-1H-imidazo[4,5-c]quinoline (31 mg, 0.072 mmol, 8.99% yield) as a beige glass. LCMS (formate) Rt 1.05 min, MH+ 433.

Workup

  1. temperaturecooled
  2. customThe mixture was evaporated in vacuo
  3. customevaporated to a brown gum
  4. dissolutionThis was dissolved in DCM (20 ml)
  5. washwashed with saturated sodium hydrogen carbonate solution
  6. washThe column was eluted with EtOAc/cyclohexane (0-100%)
  7. customthe product-containing fractions evaporated in vacuo

Sources & evidence

ORD record
ord-717fe23ce51a44a79638e9d06a256fa1
Source dataset
uspto-grants-2014_09
Patent number
US08846709B2

Reaction notes

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