Pyridine → (3Chloro-phenyl)-(pyrido[4,3-d]pyrimidin-4-yl)-amine Hydrochloride

HRID 1937384Notes

Reaction equation

HRID 1937384 reaction equation
O[C:2]1[C:3]2[CH:11]=[N:10][CH:9]=[CH:8][C:4]=2[N:5]=[CH:6][N:7]=1.N1C=CC=CC=1.[Cl:18][C:19]1[CH:20]=[C:21]([CH:23]=[CH:24][CH:25]=1)[NH2:22]>P(Cl)(Cl)(Cl)=O>[ClH:18].[Cl:18][C:19]1[CH:20]=[C:21]([NH:22][C:2]2[C:3]3[CH:11]=[N:10][CH:9]=[CH:8][C:4]=3[N:5]=[CH:6][N:7]=2)[CH:23]=[CH:24][CH:25]=1

Participants

5

Reactant 3

HCID 1049PyridineHCID 79323-ChloroanilineHCID 178518024HCID 178518024, compound

Product 1

HCID 22460894(3Chloro-phenyl)-(pyrido[4,3-d]pyrimidin-4-yl)-amine HydrochlorideYield 2.3%

Reagents, catalysts & solvents 1

HCID 24813Phosphorus oxychlorideSolvent

Conditions

Temperature
85 °C

Procedure

To 4-hydroxy-pyrido[4,3-d]pyrimidine (0.13 g, 0.90 mmol) in phosphorus oxychloride (2 ml) was added dry pyridine (0.15 ml, 1.8 mmol). A condenser and CaCl2 drying tube were attached and the suspension was refluxed for 3 hours. The final, clear solution was concentrated in vacuo (CaCl2 drying tube) and followed by a toluene chase. The resulting 4-chloro-pyrido[4,3-d]pyrimidine was dissolved in dry pyridine (1.5 ml). 3-Chloroaniline (0.096 ml, 0.90 mmol) was added, and the mixture was heated in an 85° C. oil bath for 23 hours. The reaction was cooled to ambient temperature and concentrated in vacuo. The oily residue was partitioned between CH2Cl2 and H2O, filtered, and the H2O phase extracted with CH2Cl2. The combined organic phases were dried over Na2SO4 and concentrated in vacuo. The resulting residue was purified by flash chromatography on silica gel (5 g, 40 μm mesh) using 5% methano/CH2Cl2 to afford the title compound as an off-white solid (3 mg, 1.3%). LC-MS: 257 (MH+); anal. RP18-HPLC RT: 3.85 min.

Workup

  1. customA condenser and CaCl2 drying tube were attached
  2. temperaturethe suspension was refluxed for 3 hours
  3. concentrationThe final, clear solution was concentrated in vacuo (CaCl2 drying tube)
  4. dissolutionThe resulting 4-chloro-pyrido[4,3-d]pyrimidine was dissolved in dry pyridine (1.5 ml)
  5. temperatureThe reaction was cooled to ambient temperature
  6. concentrationconcentrated in vacuo
  7. customThe oily residue was partitioned between CH2Cl2 and H2O
  8. filtrationfiltered
  9. extractionthe H2O phase extracted with CH2Cl2
  10. dry with materialThe combined organic phases were dried over Na2SO4
  11. concentrationconcentrated in vacuo
  12. customThe resulting residue was purified by flash chromatography on silica gel (5 g, 40 μm mesh)

Sources & evidence

ORD record
ord-f45a2c21ade44630bdb8781dfdc551bc
Source dataset
uspto-grants-2002_05
Patent number
US06395733B1

Reaction notes

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