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

HRID 2054332Notes

Reaction equation

HRID 2054332 reaction equation
[CH2:1]([O:5][CH2:6][C:7]1[NH:8][C:9](=O)[C:10]2[CH:16]=[CH:15][C:14]([C:17]3[C:22]([C:23]([F:26])([F:25])[F:24])=[CH:21][CH:20]=[CH:19][N:18]=3)=[N:13][C:11]=2[N:12]=1)[CH:2]([CH3:4])[CH3:3].N1C(C)=CC=CC=1C.O=P(Cl)(Cl)[Cl:38]>C(Cl)(Cl)Cl>[Cl:38][C:9]1[C:10]2[CH:16]=[CH:15][C:14]([C:17]3[C:22]([C:23]([F:26])([F:25])[F:24])=[CH:21][CH:20]=[CH:19][N:18]=3)=[N:13][C:11]=2[N:12]=[C:7]([CH2:6][O:5][CH2:1][CH:2]([CH3:4])[CH3:3])[N:8]=1

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 24813Phosphorus oxychlorideHCID 1360187452-isobutoxymethyl-7-(3-trifluoromethyl-pyridin-2-yl)-3H-pyrido[2,3-d]pyrimidin-4-one

Product 1

HCID 596557614-Chloro-2-isobutoxymethyl-7-(3-trifluoromethyl pyridin-2-yl)-pyrido[2,3-d]pyrimidine

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

Reflux a mixture of 2-isobutoxymethyl-7-(3-trifluoromethyl-pyridin-2-yl)-3H-pyrido[2,3-d]pyrimidin-4-one (0.510 g, 1.35 mmol), 2,6-lutidine (0.62 mL), and POCl3 (0.50 mL) in CHCl3 (10 mL) for 16 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 (Na2SO4) and concentrate under reduced pressure. Filter the brown residue through 2 inches of silica gel (1:1 EtOAc/hexanes eluent) and concentrate under reduced pressure to give 4-chloro-2-isobutoxymethyl-7-(3-trifluoromethyl-pyridin-2-yl)-pyrido[2,3-d]pyrimidine as yellow viscous oil.

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 (Na2SO4)
  7. concentrationconcentrate under reduced pressure
  8. filtrationFilter the brown residue through 2 inches of silica gel (1:1 EtOAc/hexanes eluent)
  9. concentrationconcentrate under reduced pressure

Sources & evidence

ORD record
ord-97c48a2a7a4a4cf9807e14909898cf1d
Source dataset
uspto-grants-2008_02
Patent number
US07329664B2

Reaction notes

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