Phosphorus oxychloride → HCID 68638665, compound

HRID 500572Notes

Reaction equation

HRID 500572 reaction equation
[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:24])[C:14]=1[NH:15][C:16]1[CH:21]=[CH:20][C:19]([Br:22])=[CH:18][C:17]=1[F:23])[N:11]=[N:10][CH:9]=[C:8]2O)=[O:4].O=P(Cl)(Cl)[Cl:28]>>[CH3:1][O:2][C:3]([C:5]1[CH:6]=[C:7]2[C:12](=[C:13]([F:24])[C:14]=1[NH:15][C:16]1[CH:21]=[CH:20][C:19]([Br:22])=[CH:18][C:17]=1[F:23])[N:11]=[N:10][CH:9]=[C:8]2[Cl:28])=[O:4]

Participants

3

Reactant 2

HCID 24813Phosphorus oxychlorideHCID 178496976HCID 178496976, compound

Product 1

HCID 68638665HCID 68638665, compound

Conditions

Temperature
80 °C

Procedure

A mixture of 7-(4-bromo-2-fluorophenylamino)-8-fluoro-4-hydroxy-cinnoline-6-carboxylic acid methyl ester (1.00 equiv.) and POCl3 (excess) is stirred for 1.5 hours at 80° C. After evaporation of POCl3 under reduced pressure, the crude material is poured into ice and neutralized to pH 7 to 8 with saturated aqueous NaHCO3. The aqueous layer is extracted with EtOAc. The organic layers is dried over MgSO4, filtered, and concentrated under reduced pressure to give the crude product that is purified by trituration or flash column chromatography to afford the desired product as necessary.

Workup

  1. customAfter evaporation of POCl3 under reduced pressure
  2. additionthe crude material is poured into ice and neutralized to pH 7 to 8 with saturated aqueous NaHCO3
  3. extractionThe aqueous layer is extracted with EtOAc
  4. dry with materialThe organic layers is dried over MgSO4
  5. filtrationfiltered
  6. concentrationconcentrated under reduced pressure
  7. customto give the crude product that
  8. customis purified by trituration or flash column chromatography

Sources & evidence

ORD record
ord-6cfb0f590775456b88bca1ce22558987
Source dataset
uspto-grants-2010_08
Patent number
US07772234B2

Reaction notes

Loading…