Water → 4-Chloro-7-(trifluoromethyl)pyrido[3,2-d]pyrimidine

HRID 925473Notes

Reaction equation

HRID 925473 reaction equation
[F:1][C:2]([F:15])([F:14])[C:3]1[CH:12]=[N:11][C:10]2[C:9](O)=[N:8][CH:7]=[N:6][C:5]=2[CH:4]=1.CCN(C(C)C)C(C)C.O=P(Cl)(Cl)[Cl:27].O>C1(C)C=CC=CC=1.CCOC(C)=O>[Cl:27][C:9]1[C:10]2[N:11]=[CH:12][C:3]([C:2]([F:15])([F:14])[F:1])=[CH:4][C:5]=2[N:6]=[CH:7][N:8]=1

Participants

7

Reactant 4

HCID 962WaterHCID 24813Phosphorus oxychlorideHCID 81531DiisopropylethylamineHCID 178518012HCID 178518012, compound

Product 1

HCID 867281584-Chloro-7-(trifluoromethyl)pyrido[3,2-d]pyrimidine

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
115 °C

Procedure

7-Trifluoromethyl-pyrido[3,2-d]pyrimidin-4-ol (300 mg, 1.39 mmol) was dissolved in toluene (5 ml). DIPEA (541 mg, 4.18 mmol) and POCl3 (641 mg, 4.18 mmol) were added and the reaction mixture was heated to 115° C. (external temperature). The reaction was cooled to rt and partioned between water (50 ml) and EtOAc (50 ml). The phases were separated and the aq phase was extracted twice with EtOAc (25 ml). The combined organic layer was washed with NaHCO3 solution and brine, treated with MgSO4 and filtered. The filtrate was concentrated, redissolved in DCM and filtered over silica and again concentrated to give the desired product as a colorless solid.

Workup

  1. temperatureThe reaction was cooled to rt
  2. customThe phases were separated
  3. extractionthe aq phase was extracted twice with EtOAc (25 ml)
  4. washThe combined organic layer was washed with NaHCO3 solution and brine
  5. additiontreated with MgSO4
  6. filtrationfiltered
  7. concentrationThe filtrate was concentrated
  8. dissolutionredissolved in DCM
  9. filtrationfiltered over silica
  10. concentrationagain concentrated

Sources & evidence

ORD record
ord-ca4095b7507b45ed978ad4c67a05182f
Source dataset
uspto-grants-2016_03
Patent number
US09284284B2

Reaction notes

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