Toluene → HCID 72218342, compound

HRID 627715Notes

Reaction equation

HRID 627715 reaction equation
[F:1][C:2]([F:15])([F:14])[C:3]1[CH:4]=[N:5][C:6]2[C:7](=O)[NH:8][CH:9]=[CH:10][C:11]=2[CH:12]=1.C1(C)C=CC=CC=1.CCN(C(C)C)C(C)C.O=P(Cl)(Cl)[Cl:34]>O.CCOC(C)=O>[Cl:34][C:7]1[N:8]=[CH:9][CH:10]=[C:11]2[C:6]=1[N:5]=[CH:4][C:3]([C:2]([F:15])([F:14])[F:1])=[CH:12]2

Participants

7

Reactant 4

HCID 1140TolueneHCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 86728153HCID 86728153, compound

Product 1

HCID 72218342HCID 72218342, compoundYield 96%

Reagents, catalysts & solvents 2

HCID 962WaterSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
115 °C

Procedure

A pressure vial was charged with 3-(trifluoromethyl)-1,7-naphthyridin-8(7H)-one (Anichem) (75 mg, 0.350 mmol), toluene (1401 μl), and Hunig's base (184 μl, 1.051 mmol). To this mixture was added POCl3 (98 μl, 1.051 mmol), and the vial was sealed. The reaction was heated at 115° C. for 2 h. After 6 h, some unreacted starting material remained. The temperature was increased to 125° C. and the reaction was stirred overnight. Upon cooling to RT, EtOAc and water were added, and the layers were separated. The aqueous portion was extracted with additional EtOAc, and the combined organic portions were dried over sodium sulfate, filtered and concentrated. The crude material was purified by silica gel chromatography using a gradient of 0-50% EtOAc in heptane to provide 8-chloro-3-(trifluoromethyl)-1,7-naphthyridine (78 mg, 0.335 mmol, 96%) as a tan solid. LC/MS (ESI+) m/z=233.1 (M+H).

Workup

  1. customthe vial was sealed
  2. temperatureThe temperature was increased to 125° C.
  3. temperatureUpon cooling to RT
  4. customthe layers were separated
  5. extractionThe aqueous portion was extracted with additional EtOAc
  6. dry with materialthe combined organic portions were dried over sodium sulfate
  7. filtrationfiltered
  8. concentrationconcentrated
  9. customThe crude material was purified by silica gel chromatography

Sources & evidence

ORD record
ord-7f00b0b2f49645d195b5e83a9ce087ef
Source dataset
uspto-grants-2016_04
Patent number
US09309263B2

Reaction notes

Loading…