6-Methoxy-3-pyridinylamine → 6-chloro-N-(6-methoxy-3-pyridinyl)-Pyrido[3,2-d]pyrimidin-4-amine

HRID 1485535Notes

Reaction equation

HRID 1485535 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[CH:7][N:8]=[C:9](OC3CCOCC3)[C:10]=2[N:11]=1.[CH3:19][O:20][C:21]1[N:26]=[CH:25][C:24]([NH2:27])=[CH:23][CH:22]=1.C([O-])(=O)C.[Na+]>CCOC(C)=O>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[N:6]=[CH:7][N:8]=[C:9]([NH:27][C:24]3[CH:25]=[N:26][C:21]([O:20][CH3:19])=[CH:22][CH:23]=3)[C:10]=2[N:11]=1

Participants

5

Reactant 3

HCID 811216-Methoxy-3-pyridinylamineHCID 517045Sodium AcetateHCID 866710656-chloro-4-[(tetrahydro-2H-pyran-4-yl)oxy]-Pyrido[3,2-d]pyrimidine2×

Product 1

HCID 866710776-chloro-N-(6-methoxy-3-pyridinyl)-Pyrido[3,2-d]pyrimidin-4-amineYield 59.1%

Reagents, catalysts & solvents 1

HCID 8857Ethyl AcetateSolvent

Procedure

A mixture of 4,6-dichloropyrido[3,2-d]pyrimidine (Intermediate 1, step D) (0.100 g, 0.500 mmol), 6-methoxypyridin-3-amine (0.155 g, 1.250 mmol) and sodium acetate (0.123 g, 1.50 mmol) in 5 ml of solvent (THF:H2O=1:1) was refluxed for 1 hour. The reaction mixture was diluted with EtOAc. The organics were washed with brine, dried over Na2SO4, filtered and concentrated. The crued was purified by column chromatography on SiO2 (Hex:EtOAc=1:1) to get 6-chloro-N-(6-methoxypyridin-3-yl)pyrido[3,2-d]pyrimidin-4-amine (0.085 g, 59%) as a yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 3.97 (3H, s), 6.85 (1H, d, J=8.8 Hz), 7.71 (1H, d, J=8.8 Hz), 8.14 (1H, d, J=8.8 Hz), 8.20 (1H, dd, J=2.8, 8.8 Hz), 8.55 (1H, d, J=2.8 Hz), 8.67 (1H, br s), 8.73 (1H, s).

Workup

  1. temperaturewas refluxed for 1 hour
  2. washThe organics were washed with brine
  3. dry with materialdried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe crued was purified by column chromatography on SiO2 (Hex:EtOAc=1:1)

Sources & evidence

ORD record
ord-e3220c8cec404e3db1000fb78cc93315
Source dataset
uspto-grants-2016_08
Patent number
US09422298B2

Reaction notes

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