Iodine → HCID 70498054, compound

HRID 244308Notes

Reaction equation

HRID 244308 reaction equation
[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][C:9]=2[F:15])[N:5]=[C:4]([C:16]([O:18][CH3:19])=[O:17])[CH:3]=1.[I:20](O)(=O)(=O)=O.II.S([O-])([O-])=O.[Na+].[Na+]>CO.ClCCl>[NH2:1][C:2]1[N:7]=[C:6]([C:8]2[CH:13]=[CH:12][C:11]([Cl:14])=[CH:10][C:9]=2[F:15])[N:5]=[C:4]([C:16]([O:18][CH3:19])=[O:17])[C:3]=1[I:20]

Participants

7

Reactant 4

HCID 807IodineHCID 24437Sodium SulfiteHCID 65185Metaperiodic acidHCID 67210655Methyl 6-amino-2-(4-chloro-2-fluorophenyl)pyrimidine-4-carboxylate

Product 1

HCID 70498054HCID 70498054, compoundYield 38.9%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

Methyl 6-amino-2-(4-chloro-2-fluorophenyl)pyrimidine-4-carboxylate (6.17 g, 21.91 mmol, see US 20090088322 for preparation) was diluted with methanol (100 ml). Periodic acid (2.10 g, 9.21 mmol) and iodine (5.26 g, 20.72 mmol) were added and the reaction was heated at reflux overnight. The cooled reaction mixture was diluted with dichloromethane and poured into a 1N solution of sodium sulfite. The aqueous phase was extracted with dichloromethane. The combined organic phases were washed with 1N sodium sulfite, washed with saturated sodium chloride, dried over magnesium sulfate, filtered, and concentrated onto celite. Purification by flash chromatography (SiO2, 30% EtOAc:Hex) provided the title compound (1.46 g, 16% yield) as a white solid: 1H NMR (400 MHz, DMSO-d6) d 3.89 (s, 3H), 7.34-7.46 (m, 1H), 7.53 (dd, J=10.7, 2.0 Hz, 1H), 7.89 (t, J=8.4 Hz, 1H); 19F NMR (376 MHz, DMSO-d6) d −110.23; ESIMS m/z 408 ([M+H]+), 406 ([M−H]−).

Workup

  1. temperaturethe reaction was heated
  2. temperatureat reflux overnight
  3. customThe cooled reaction mixture
  4. extractionThe aqueous phase was extracted with dichloromethane
  5. washThe combined organic phases were washed with 1N sodium sulfite
  6. washwashed with saturated sodium chloride
  7. dry with materialdried over magnesium sulfate
  8. filtrationfiltered
  9. concentrationconcentrated onto celite
  10. customPurification by flash chromatography (SiO2, 30% EtOAc:Hex)

Sources & evidence

ORD record
ord-ddb58b04aba749318b25ffbc9307ce6d
Source dataset
uspto-grants-2014_02
Patent number
US08658568B2

Reaction notes

Loading…