N,N-Dimethylaniline → 4-Chloro-5,6,7,8-tetrahydro-6-(5-methylpyridin-2-yl)pyrido[4,3-d]pyrimidine

HRID 241841Notes

Reaction equation

HRID 241841 reaction equation
[CH3:1][C:2]1[CH:3]=[CH:4][C:5]([N:8]2[CH2:18][CH2:17][C:11]3[N:12]=[CH:13][NH:14][C:15](=O)[C:10]=3[CH2:9]2)=[N:6][CH:7]=1.P(Cl)(Cl)([Cl:21])=O.CN(C)C1C=CC=CC=1.C(=O)(O)[O-].[Na+]>C(Cl)Cl.ClCCCl>[Cl:21][C:15]1[C:10]2[CH2:9][N:8]([C:5]3[CH:4]=[CH:3][C:2]([CH3:1])=[CH:7][N:6]=3)[CH2:18][CH2:17][C:11]=2[N:12]=[CH:13][N:14]=1

Participants

7

Reactant 4

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 1359789575,6,7,8-Tetrahydro-6-(5-methylpyridin-2-yl)pyrido[4,3-d]pyrimidin-4(3H)-one

Product 1

HCID 593464574-Chloro-5,6,7,8-tetrahydro-6-(5-methylpyridin-2-yl)pyrido[4,3-d]pyrimidine

Reagents, catalysts & solvents 2

HCID 111,2-DichloroethaneSolventHCID 6344DichloromethaneSolvent

Procedure

Into a 250 mL round bottom flask was combined 5,6,7,8-tetrahydro-6-(5-methylpyridin-2-yl)pyrido[4,3-d]pyrimidin-4(3H)-one (0.250 g, 1.03 mmol), phosphoryl chloride (0.8 mL, 8 mmol), and 1,2-dichloroethane (10 mL). N,N-Dimethylaniline (0.01 g, 0.1 mmol) was added dropwise and the mixture was heated at reflux for 2 hours. The mixture was reduced in vacuo to yield a dark brown oil. The oil was taken up in methylene chloride (50 mL) and poured over ice. The mixture was carefully neutralized using sat. aq. sodium bicarbonate. The organic layer was separated and dried over sodium sulfate and reduced in vacuo. The residue was purified by flash chromatography on silica gel (0-10% methanol/methylene chloride) to give a bright yellow solid. (0.141 g, 52.4%).

Workup

  1. customInto a 250 mL round bottom flask was combined
  2. temperaturethe mixture was heated
  3. temperatureat reflux for 2 hours
  4. customto yield a dark brown oil
  5. additionpoured over ice
  6. customThe organic layer was separated
  7. dry with materialdried over sodium sulfate
  8. customThe residue was purified by flash chromatography on silica gel (0-10% methanol/methylene chloride)
  9. customto give a bright yellow solid

Sources & evidence

ORD record
ord-7a0f5aae06d04ce898ab01c841ac70ea
Source dataset
uspto-grants-2014_02
Patent number
US08653091B2

Reaction notes

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