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

HRID 971213Notes

Reaction equation

HRID 971213 reaction equation
[Cl:1][C:2]1[C:3]([N:8]2[CH2:17][CH2:16][C:15]3[C:14](=O)[NH:13][CH:12]=[N:11][C:10]=3[CH2:9]2)=[N:4][CH:5]=[CH:6][CH:7]=1.O=P(Cl)(Cl)[Cl:21].CN(C)C1C=CC=CC=1.C([O-])(O)=O.[Na+]>ClCCCl.C(OCC)(=O)C.O>[Cl:21][C:14]1[C:15]2[CH2:16][CH2:17][N:8]([C:3]3[C:2]([Cl:1])=[CH:7][CH:6]=[CH:5][N:4]=3)[CH2:9][C:10]=2[N:11]=[CH:12][N:13]=1

Participants

8

Reactant 4

HCID 949N,N-DimethylanilineHCID 24813Phosphorus oxychlorideHCID 516892Sodium BicarbonateHCID 1359974627-(3-Chloropyridin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidin-4(3H)-one

Product 1

HCID 590214784-Chloro-7-(3-chloropyridin-2-yl)-5,6,7,8-tetrahydropyrido[3,4-d]pyrimidineYield 73%

Reagents, catalysts & solvents 3

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

Conditions

Temperature
0 °C

Procedure

7-(3-Chloro-pyridin-2-yl)-5,6,7,8-tetrahydro-3H-pyrido[3,4-d]pyrimidin-4-one (1 g crude, 3.8 mmol) was dissolved in anhydrous 1,2-dichloroethane (60 ml) and stirred under N2(g) atmosphere. The mixture was cooled to 0° C. and POCl3 (2.8 ml, 31 mmole) was added dropwise, followed by N,N-dimethylaniline (0.49 ml, 3.8 mole). The mixture was warmed to room temperature and brought to reflux for 2 hrs. After stirring at room temperature overnight, J=the solvents were removed under vacuum and evaporated 3× with xylenes to give a red residue. The residue was dissolved in ethyl acetate and water and neutralized using 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 a brown oil (780 mg; 73%).

Workup

  1. temperatureThe mixture was warmed to room temperature
  2. temperatureto reflux for 2 hrs
  3. stirringAfter stirring at room temperature overnight
  4. customJ=the solvents were removed under vacuum
  5. customevaporated 3× with xylenes
  6. customto give a red residue
  7. washthe organic layer was washed with water and brine
  8. dry with materialThe organic layer was dried over Na2SO4
  9. customthe solvents were removed under vacuum
  10. customThe resulting red residue was purified

Sources & evidence

ORD record
ord-191a8932b5464ebf8959e20f367e7602
Source dataset
uspto-grants-2007_12
Patent number
US07312330B2

Reaction notes

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