2,6-Lutidine → HCID 22030241, compound

HRID 968594Notes

Reaction equation

HRID 968594 reaction equation
[CH3:1][CH:2]1[O:7][CH:6]([CH3:8])[CH2:5][N:4]([CH2:9][C:10]2[N:11]=[C:12](O)[C:13]3[CH:19]=[N:18][C:17]([C:20]4[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=4[C:26]([F:29])([F:28])[F:27])=[CH:16][C:14]=3[N:15]=2)[CH2:3]1.N1C(C)=CC=CC=1C.O=P(Cl)(Cl)[Cl:41]>C(Cl)(Cl)Cl>[Cl:41][C:12]1[C:13]2[CH:19]=[N:18][C:17]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][C:21]=3[C:26]([F:28])([F:27])[F:29])=[CH:16][C:14]=2[N:15]=[C:10]([CH2:9][N:4]2[CH2:5][CH:6]([CH3:8])[O:7][CH:2]([CH3:1])[CH2:3]2)[N:11]=1

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 24813Phosphorus oxychlorideHCID 178430445HCID 178430445, compound

Product 1

HCID 22030241HCID 22030241, compound

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

Reflux a mixture of 2-(2,6-dimethyl-morpholin-4-ylmethyl)-7-(2-trifluoromethyl-phenyl)-pyrido[4,3-d]-pyrimidin-4-ol (0.6 g), 2,6-lutidine (0.62 g), and POCl3 (1.1 g) in CHCl3 (15 mL) for 20 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-(2,6-dimethyl-morpholin-4-ylmethyl)-7-(2-trifluoromethyl-phenyl)-pyrido[4,3-d]pyrimidine.

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-526ab34bccac4ef5b479e8106750f604
Source dataset
uspto-grants-2007_12
Patent number
US07304059B2

Reaction notes

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