2,6-Lutidine → 4-Chloro-6-(3,4-dimethoxyphenyl)-2-methylpyrido[3,2-d]pyrimidine

HRID 1517392Notes

Reaction equation

HRID 1517392 reaction equation
[CH3:1][C:2]1[NH:3][C:4](=O)[C:5]2[N:11]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=3)[CH:9]=[CH:8][C:6]=2[N:7]=1.N1C(C)=CC=CC=1C.O=P(Cl)(Cl)[Cl:33]>C1(C)C=CC=CC=1.C(OCC)(=O)C>[CH3:1][C:2]1[N:3]=[C:4]([Cl:33])[C:5]2[N:11]=[C:10]([C:12]3[CH:17]=[CH:16][C:15]([O:18][CH3:19])=[C:14]([O:20][CH3:21])[CH:13]=3)[CH:9]=[CH:8][C:6]=2[N:7]=1

Participants

6

Reactant 3

HCID 79372,6-LutidineHCID 24813Phosphorus oxychlorideHCID 1362700196-(3,4-Dimethoxyphenyl)-2-methylpyrido[3,2-d]pyrimidin-4(1H)-one

Product 1

HCID 714077014-Chloro-6-(3,4-dimethoxyphenyl)-2-methylpyrido[3,2-d]pyrimidineYield 75%

Reagents, catalysts & solvents 2

HCID 1140TolueneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of 2-methyl-6-(3,4-dimethoxyphenyl)-pyrido[3,2-d]pyrimidin-4(3H)-one (416 mg, 1.4 mmol) in toluene (28 ml) was added 2,6-lutidine (490 μl, 4.2 mmol) and POCl3 (4.2 mmol, 385 μl). The mixture was refluxed under nitrogen atmosphere for 5 hours. The reaction mixture was cooled down, diluted with ethyl acetate (50 ml) and extracted with a saturated sodium bicarbonate solution. The combined organic layers were evaporated in vacuo and the residue was purified by silica gel column chromatography (the mobile phase being an ethyl acetate/hexane mixture in a ratio of 15:85), resulting in the pure title compound (330 mg, yield 75%) which was characterised by its mass spectrum as follows: MS (m/z): 316, 318 ([M+H]+, 100).

Workup

  1. temperatureThe mixture was refluxed under nitrogen atmosphere for 5 hours
  2. temperatureThe reaction mixture was cooled down
  3. extractionextracted with a saturated sodium bicarbonate solution
  4. customThe combined organic layers were evaporated in vacuo
  5. customthe residue was purified by silica gel column chromatography (the mobile phase

Sources & evidence

ORD record
ord-34c9d24c048149ab9e048c5b2bcdb65e
Source dataset
uspto-grants-2012_07
Patent number
US08232278B2

Reaction notes

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