2,6-Lutidine → 4-Chloro-2-methoxymethyl-7-(3-trifluoromethyl-pyridin-2-yl)-pyrido[2,3-d]pyrimidine

HRID 2054335Notes

Reaction equation

HRID 2054335 reaction equation
[CH3:1][O:2][CH2:3][C:4]1[NH:5][C:6](=O)[C:7]2[CH:13]=[CH:12][C:11]([C:14]3[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][CH:17]=[CH:16][N:15]=3)=[N:10][C:8]=2[N:9]=1.N1C(C)=CC=CC=1C.O=P(Cl)(Cl)[Cl:35]>C(Cl)(Cl)Cl>[Cl:35][C:6]1[C:7]2[CH:13]=[CH:12][C:11]([C:14]3[C:19]([C:20]([F:23])([F:22])[F:21])=[CH:18][CH:17]=[CH:16][N:15]=3)=[N:10][C:8]=2[N:9]=[C:4]([CH2:3][O:2][CH3:1])[N:5]=1

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 24813Phosphorus oxychlorideHCID 1360187442-methoxymethyl-7-(3-trifluoromethyl-pyridin-2-yl)-3H-pyrido[2,3-d]pyrimidin-4-one

Product 1

HCID 596557544-Chloro-2-methoxymethyl-7-(3-trifluoromethyl-pyridin-2-yl)-pyrido[2,3-d]pyrimidine

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

Reflux a mixture of 2-methoxymethyl-7-(3-trifluoromethyl-pyridin-2-yl)-3H-pyrido[2,3-d]pyrimidin-4-one (0.500 g, 1.49 mmol), 2,6-lutidine (0.69 mL), and POCl3 (0.555 mL) in CHCl3 (10 mL) for 5 hours. Cool the mixture and concentrate under reduced pressure. Partition the residue between EtOAc and saturated NaHCO3 solution. Wash the EtOAc portion with additional NaHCO3 and then dry (MgSO4) and concentrate under reduced pressure. Purified the crude by flash column chromatography on a silica gel (EtOAc eluent) and concentrate under reduced pressure to give 4-chloro-2-methoxymethyl-7-(3-trifluoromethyl-pyridin-2-yl)-pyrido[2,3-d]pyrimidine as a white solid.

Workup

  1. temperatureReflux
  2. temperatureCool the mixture
  3. concentrationconcentrate under reduced pressure
  4. customPartition the residue between EtOAc and saturated NaHCO3 solution
  5. washWash the EtOAc portion with additional NaHCO3
  6. dry with materialdry (MgSO4)
  7. concentrationconcentrate under reduced pressure
  8. customPurified the crude by flash column chromatography on a silica gel (EtOAc eluent)
  9. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-486f357919724490ac403213ee5a9c51
Source dataset
uspto-grants-2008_02
Patent number
US07329664B2

Reaction notes

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