Dimethylformamide → 4-CHLORO-6-FLUOROPYRIDO[3,4-D]PYRIMIDINE

HRID 428365Notes

Reaction equation

HRID 428365 reaction equation
[F:1][C:2]1[N:12]=[CH:11][C:5]2[N:6]=[CH:7][NH:8][C:9](=O)[C:4]=2[CH:3]=1.S(Cl)([Cl:15])=O.CN(C)C=O>ClCCCl>[Cl:15][C:9]1[C:4]2[CH:3]=[C:2]([F:1])[N:12]=[CH:11][C:5]=2[N:6]=[CH:7][N:8]=1

Participants

5

Reactant 3

HCID 6228DimethylformamideHCID 24386Thionyl ChlorideHCID 1354173706-fluoropyrido[3,4-d]pyrimidin-4-ol

Product 1

HCID 106790414-CHLORO-6-FLUOROPYRIDO[3,4-D]PYRIMIDINEYield 91%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

A stirred suspension of 30.0 g (182 mmol) of 6-fluoropyrido[3,4-d]pyrimidin-4(3H)-one in 182 mL of 1,2-dichloroethane was treated successively with 182 mL of thionyl chloride, then ca. 1 mL of N,N-dimethyl-formamide. The mixture was heated at reflux for 2.5 hours, then concentrated to a solid that was coevaporated twice with 1,2-dichloroethane. The residual dark brown solids were dissolved in dichloromethane, and the solution was filtered through a short pad of silica gel eluting with dichloromethane. Concentration of product fractions afforded 30.5 g (91%) of pure product after drying. Crystallization of a small sample from tert-butyl methyl ether gave product of mp 75-76° C. 1H NMR (CDCl3): δ9.29 (s, 1H, 9.16 (s, 1H), and 7.65 (dd, J=0.7 Hz, 2.0 Hz, 1H).

Workup

  1. temperatureThe mixture was heated
  2. temperatureat reflux for 2.5 hours
  3. concentrationconcentrated to a solid
  4. dissolutionThe residual dark brown solids were dissolved in dichloromethane
  5. filtrationthe solution was filtered through a short pad of silica gel eluting with dichloromethane

Sources & evidence

ORD record
ord-5f689288824047a8a2cdd3a4b11f1379
Source dataset
uspto-grants-2001_11
Patent number
US06313292B1

Reaction notes

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