Phosphorus oxychloride → 4-Chloro-7-methylpyrido[2,3-d]pyrimidine

HRID 1192407Notes

Reaction equation

HRID 1192407 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]2[C:10](O)=[N:9][CH:8]=[N:7][C:6]=2[N:12]=1.CCN(C(C)C)C(C)C.O=P(Cl)(Cl)[Cl:24]>ClCCCl>[Cl:24][C:10]1[C:5]2[CH:4]=[CH:3][C:2]([CH3:1])=[N:12][C:6]=2[N:7]=[CH:8][N:9]=1

Participants

5

Reactant 3

HCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 178422981HCID 178422981, compound

Product 1

HCID 601461054-Chloro-7-methylpyrido[2,3-d]pyrimidineYield 76%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a solution of 7-Methyl-pyrido[2,3-d]pyrimidin-4-ol (0.78 g, 4.84 mmol) in DCE (30 mL) was added DIEA (1.0 mL, 1.19 mmol), followed by POCl3 (2.4 mL, 26.1 mmol). The mixture was refluxed overnight. After cooling, the solvent was removed and the residue was dissolved in water (50 mL) and extracted with ethyl acetate (3×100 mL). The organic phase was dried and concentrated. The residue was subject to column chromatography, eluted by hexane/ethyl acetate (2:1) to give 4-Chloro-7-methyl-pyrido[2,3-d]pyrimidine (0.66 g, 76%). 1H NMR (CDCl3, 400 MHz) δ 9.22 (s, 1H), 8.49 (d, J=8.8 Hz, 1H), 7.57 (d, J=8.4 Hz, 1H), 2.88 (s, 3H). MS (APCI+) [M+H]+180.

Workup

  1. temperatureThe mixture was refluxed overnight
  2. temperatureAfter cooling
  3. customthe solvent was removed
  4. dissolutionthe residue was dissolved in water (50 mL)
  5. extractionextracted with ethyl acetate (3×100 mL)
  6. customThe organic phase was dried
  7. concentrationconcentrated
  8. washeluted by hexane/ethyl acetate (2:1)

Sources & evidence

ORD record
ord-9866281b1c1c4cbd89798aff5693e951
Source dataset
uspto-grants-2014_03
Patent number
US08680114B2

Reaction notes

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