Phosphorus oxychloride → HCID 58456107, compound

HRID 410634Notes

Reaction equation

HRID 410634 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([NH:20][C:21]2[N:26]=[C:25](O)[CH:24]=[CH:23][N:22]=2)[CH:5]=[C:6]([C:8]2[S:12][C:11]([C:13]([OH:19])([CH3:18])[C:14]([F:17])([F:16])[F:15])=[N:10][CH:9]=2)[CH:7]=1.P(Cl)(Cl)([Cl:30])=O>O1CCOCC1>[Cl:30][C:25]1[CH:24]=[CH:23][N:22]=[C:21]([NH:20][C:4]2[CH:5]=[C:6]([C:8]3[S:12][C:11]([C:13]([OH:19])([CH3:18])[C:14]([F:17])([F:15])[F:16])=[N:10][CH:9]=3)[CH:7]=[C:2]([CH3:1])[CH:3]=2)[N:26]=1

Participants

4

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178428313HCID 178428313, compound

Product 1

HCID 58456107HCID 58456107, compoundYield 75.7%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Procedure

The product of Step 1 (145 mg, 0.37 mmol) was taken up in dioxane (2 mL) and phosphorus oxychloride (1.02 mL, 11 mmol) was added. The mixture was heated at reflux for 1.5 hours. The reaction was then cooled to room temperature, poured over ice, and quenched by dropwise addition of 10 N aqueous sodium hydroxide (until pH=8). Ethyl acetate was added and the layers were separated. The aqueous layer was extracted once more with ethyl acetate. The combined organics were dried over magnesium sulfate, filtered, and concentrated under reduced pressure. The residue was purified by Chromatography on silica gel (0-50% ethyl acetate/hexanes) to afford 114 mg (0.28 mmol, 75%) of 2-(5-{3-[(4-chloropyrimidin-2-yl)amino]-5-methylphenyl}-1,3-thiazol-2-yl)-1,1,1-trifluoropropan-2-ol as a white solid. MS ESI: [M+H]+ m/z 415.0. 1H NMR (500 MHz, DMSO-d6) δ 10.10 (s, 1H), 8.47 (d, J=5 Hz, 1H), 8.08 (s, 1H), 7.88 (s, 1H), 7.67 (s, 1H), 7.50 (s, 1H), 7.17 (s, 1H), 6.99 (d, J=5 Hz, 1H), 2.32 (s, 3H), 1.76 (s, 3H). rhSYK activity=+++

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 1.5 hours
  3. additionpoured over ice
  4. customquenched by dropwise addition of 10 N aqueous sodium hydroxide (until pH=8)
  5. additionEthyl acetate was added
  6. customthe layers were separated
  7. extractionThe aqueous layer was extracted once more with ethyl acetate
  8. dry with materialThe combined organics were dried over magnesium sulfate
  9. filtrationfiltered
  10. concentrationconcentrated under reduced pressure
  11. customThe residue was purified by Chromatography on silica gel (0-50% ethyl acetate/hexanes)

Sources & evidence

ORD record
ord-83806c3827bb4af8b46aec2b0f5fa44b
Source dataset
uspto-grants-2014_06
Patent number
US08759366B2

Reaction notes

Loading…