2,6-Lutidine → 4-Chloro-6-(4-methoxy-3-methylphenyl)pyrido[3,2-d]pyrimidine

HRID 1517415Notes

Reaction equation

HRID 1517415 reaction equation
[CH3:1][C:2]1[CH:3]=[C:4]([C:10]2[CH:11]=[CH:12][C:13]3[N:14]=[CH:15][NH:16][C:17](=O)[C:18]=3[N:19]=2)[CH:5]=[CH:6][C:7]=1[O:8][CH3:9].P(Cl)(Cl)([Cl:23])=O.N1C(C)=CC=CC=1C>C1(C)C=CC=CC=1>[Cl:23][C:17]1[C:18]2[N:19]=[C:10]([C:4]3[CH:5]=[CH:6][C:7]([O:8][CH3:9])=[C:2]([CH3:1])[CH:3]=3)[CH:11]=[CH:12][C:13]=2[N:14]=[CH:15][N:16]=1

Participants

5

Reactant 3

HCID 79372,6-LutidineHCID 24813Phosphorus oxychlorideHCID 1362700176-(4-Methoxy-3-methylphenyl)pyrido[3,2-d]pyrimidin-4(1H)-one

Product 1

HCID 714076974-Chloro-6-(4-methoxy-3-methylphenyl)pyrido[3,2-d]pyrimidineYield 74.5%

Reagents, catalysts & solvents 1

HCID 1140TolueneSolvent

Procedure

To a suspension of 6-(3-methyl-4-methoxyphenyl)-pyrido[3,2-d]pyrimidin-4(3H)one (1.41 mmole) in toluene (80 ml) was added phosphorus oxychloride (4.23 mmole) and 2,6-lutidine (4.23 mmole). The reaction mixture was refluxed for 16 hours until a black solution was obtained. After evaporation to dryness, the residue was redissolved in ethyl acetate and extracted with a saturated sodium bicarbonate solution. The combined organic layers were evaporated in vacuo. The residue was purified by silica gel column chromatography (the mobile phase being a ethylacetate/hexane mixture in a ratio gradually ranging from 2:8 to 3:7), resulting in the pure title compound (300 mg, yield 74%) which was characterized by its mass spectrum as follows: MS (m/z): 287 ([M+H]+, 100).

Workup

  1. temperatureThe reaction mixture was refluxed for 16 hours until a black solution
  2. customwas obtained
  3. customAfter evaporation to dryness
  4. dissolutionthe residue was redissolved in ethyl acetate
  5. extractionextracted with a saturated sodium bicarbonate solution
  6. customThe combined organic layers were evaporated in vacuo
  7. customThe residue was purified by silica gel column chromatography (the mobile phase

Sources & evidence

ORD record
ord-2351ef0a844a48dc83a13f068c9e8c7b
Source dataset
uspto-grants-2012_07
Patent number
US08232278B2

Reaction notes

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