Phosphorus oxychloride → HCID 86655258, compound

HRID 1890321Notes

Reaction equation

HRID 1890321 reaction equation
[CH3:1][S:2]([O:5][C:6]1[N:11]=[C:10]2[N:12]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[O:22][C:23]([F:26])([F:25])[F:24])[C:13](O)=[N:14][C:9]2=[CH:8][CH:7]=1)(=[O:4])=[O:3].P(Cl)(Cl)([Cl:29])=O>>[CH3:1][S:2]([O:5][C:6]1[N:11]=[C:10]2[N:12]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][C:17]=3[O:22][C:23]([F:26])([F:25])[F:24])[C:13]([Cl:29])=[N:14][C:9]2=[CH:8][CH:7]=1)(=[O:4])=[O:3]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178505197HCID 178505197, compound

Product 1

HCID 86655258HCID 86655258, compound

Conditions

Temperature
80 °C

Procedure

2-Hydroxy-3-(2-(trifluoromethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl methanesulfonate (0.50 g, 1.3 mmol) taken up in phosphoryl trichloride (3.0 mL) was heated in a sealed tube to 80° C. for 48 h. The mixture was concentrated under reduced pressure and NaHCO3 was added to the residue until it turned basic. The solution was further diluted with water and extracted with EtOAc (3×). The combined organic extracts were dried over MgSO4 and concentrated under reduced pressure. The residue was purified column chromatography to give 2-chloro-3-(2-(trifluoromethoxy)phenyl)-3H-imidazo[4,5-b]pyridin-5-yl methanesulfonate, which was dissolved in a 1:4:1 solution of 1 M LiOH/THF/MeOH (10 mL) and stirred at room temperature for 1 hour. The mixture was concentrated under reduced pressure and the remaining was acidified with 1 N HCl. The resulting precipitate was collected by vacuum filtration and purified via preparative HPLC to give the title compound (0.11 g, 0.32 mmol, 25%). LCMS m/z=330.2 [M+H]+, 1H NMR (400 MHz, methanol-d4) δ ppm 6.70 (d, J=8.7 Hz, 1H), 7.58-7.68 (m, 3H), 7.73 (m, 1H), 7.90 (d, J=8.7 Hz, 1H).

Workup

  1. concentrationThe mixture was concentrated under reduced pressure and NaHCO3
  2. additionwas added to the residue until it
  3. additionThe solution was further diluted with water
  4. extractionextracted with EtOAc (3×)
  5. dry with materialThe combined organic extracts were dried over MgSO4
  6. concentrationconcentrated under reduced pressure
  7. customThe residue was purified column chromatography

Sources & evidence

ORD record
ord-0b9bbdd929a949c886a2683bc7a7a55d
Source dataset
uspto-grants-2013_08
Patent number
US08507473B2

Reaction notes

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