4-Amino-3,5-dimethylisoxazole → 6-chloro-N-(3,5-dimethyl-4-isoxazolyl)-Pyrido[3,2-d]pyrimidin-4-amine

HRID 1182954Notes

Reaction equation

HRID 1182954 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][C:20]1[C:24]([NH2:25])=[C:23]([CH3:26])[O:22][N:21]=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:25][C:24]3[C:20]([CH3:19])=[N:21][O:22][C:23]=3[CH3:26])[C:10]=2[N:11]=1

Participants

5

Reactant 3

HCID 1820404-Amino-3,5-dimethylisoxazoleHCID 517045Sodium AcetateHCID 866710656-chloro-4-[(tetrahydro-2H-pyran-4-yl)oxy]-Pyrido[3,2-d]pyrimidine2×

Product 1

HCID 866710766-chloro-N-(3,5-dimethyl-4-isoxazolyl)-Pyrido[3,2-d]pyrimidin-4-amineYield 59.5%

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), 3,5-dimethylisoxazol-4-amine (0.140 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 crude was purified by column chromatography on SiO2 (Hex:EtOAc=1:1) to get N-(6-chloropyrido[3,2-d]pyrimidin-4-yl)-3,5-dimethylisoxazol-4-amine (0.082 g, 59%) as a yellow solid. 1H-NMR (CDCl3, Varian 400 MHz) δ 2.24 (3H, s), 2.40 (3H, s), 7.74 (1H, d, J=8.8 Hz), 7.93 (1H, brs), 8.16 ((1H, d, J=8.8 Hz), 8.69 (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 crude was purified by column chromatography on SiO2 (Hex:EtOAc=1:1)

Sources & evidence

ORD record
ord-4f05b9cd68b74a28b940164b8b454ea9
Source dataset
uspto-grants-2014_03
Patent number
US08664230B2

Reaction notes

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