N,N-Dimethylaniline → 7-Benzyl-4-chloro-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidine

HRID 2219906Notes

Reaction equation

HRID 2219906 reaction equation
[CH2:1]([N:8]1[CH2:17][CH2:16][C:15]2[C:14](=O)[NH:13][CH:12]=[N:11][C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.O=P(Cl)(Cl)[Cl:21].CN(C)C1C=CC=CC=1.C([O-])(O)=O.[Na+]>ClCCCl.C(OCC)(=O)C.O>[CH2:1]([N:8]1[CH2:17][CH2:16][C:15]2[C:14]([Cl:21])=[N:13][CH:12]=[N:11][C:10]=2[CH2:9]1)[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1

Participants

8

Reactant 4

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 1357235075,6,7,8-Tetrahydro-7-(phenylmethyl)pyrido(3,4-d)pyrimidin-4(3H)-one

Product 1

HCID 219588387-Benzyl-4-chloro-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidineYield 38%

Reagents, catalysts & solvents 3

HCID 111,2-DichloroethaneSolventHCID 962WaterSolventHCID 8857Ethyl AcetateSolvent2×

Procedure

7-Benzyl-5,6,7,8-tetrahydro-3H-pyrido[3,4-d]pyrimidin-4-one (9.4 g, 39 mmol) was dissolved in anhydrous 1,2-dichloroethane and stirred under N2(g) atmosphere. To the mixture was added POCl3 (29 mL, 312 mmol), followed by N,N-dimethylaniline (4.75 g, 39 mmol). The mixture was refluxed for 2 h and the solvents were removed under vacuum to give a red residue. The residue was dissolved in 20 mL of ethyl acetate and 20 ml of water was added. The solution was neutralized with ice and solid NaHCO3. After neutralization, ethyl acetate was added and the organic layer was washed with water and brine. The organic layer was dried over Na2SO4 and the solvents were removed under vacuum. The resulting red residue was purified using a gradient of ethyl acetate:hexane (0-100%) to give the desired compound as yellow crystals (3.8 g, 38%).

Workup

  1. temperatureThe mixture was refluxed for 2 h
  2. customthe solvents were removed under vacuum
  3. customto give a red residue
  4. washthe organic layer was washed with water and brine
  5. dry with materialThe organic layer was dried over Na2SO4
  6. customthe solvents were removed under vacuum
  7. customThe resulting red residue was purified

Sources & evidence

ORD record
ord-df8c1d1cbb394fb79121afe6105ee08a
Source dataset
uspto-grants-2008_08
Patent number
US07414131B2

Reaction notes

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