Morpholine → 3-Bromo-8-(4-morpholinyl)pyrido[2,3-d]pyridazine

HRID 2357529Notes

Reaction equation

HRID 2357529 reaction equation
[Br:1][C:2]1[CH:12]=[N:11][C:5]2[C:6](=O)[NH:7][N:8]=[CH:9][C:4]=2[CH:3]=1.P(Cl)(Cl)(Cl)=O.[NH:18]1[CH2:23][CH2:22][O:21][CH2:20][CH2:19]1>C(Cl)(Cl)Cl>[Br:1][C:2]1[CH:12]=[N:11][C:5]2=[C:6]([N:18]3[CH2:23][CH2:22][O:21][CH2:20][CH2:19]3)[N:7]=[N:8][CH:9]=[C:4]2[CH:3]=1

Participants

5

Reactant 3

HCID 8083MorpholineHCID 24813Phosphorus oxychlorideHCID 684549573-Bromopyrido[2,3-d]pyridazin-8(7H)-one

Product 1

HCID 684552693-Bromo-8-(4-morpholinyl)pyrido[2,3-d]pyridazine

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Conditions

Temperature
95 °C

Procedure

A mixture of 3-bromopyrido[2,3-d]pyridazin-8(7H)-one (0.206 g, 0.91 mmol) and phosphorus oxychloride (5.00 ml, 55 mmol) was heated at 95° C. After 2 h the reaction was cooled to 25° C. and diluted with 30 mL of CHCl3. The solution was cooled to 0° C. and the solid was filtered and washed with CHCl3. The filtrate was concentrated to dryness and azeotroped with toluene (2×). The residue was dissolved in CH3CN and heated with morpholine (0.079 ml, 0.91 mmol) at 190° C. for 15 min in the microwave. The crude material was purified by flash chromatography eluting with 2M NH3 in MeOH:CH2Cl2 (0:1→1:24) to give the title compound as an orange amorphous solid. MS m/z: 295.0 [M+1].

Workup

  1. temperatureAfter 2 h the reaction was cooled to 25° C.
  2. temperatureThe solution was cooled to 0° C.
  3. filtrationthe solid was filtered
  4. washwashed with CHCl3
  5. concentrationThe filtrate was concentrated to dryness
  6. customazeotroped with toluene (2×)
  7. dissolutionThe residue was dissolved in CH3CN
  8. customThe crude material was purified by flash chromatography
  9. washeluting with 2M NH3 in MeOH:CH2Cl2 (0:1→1:24)

Sources & evidence

ORD record
ord-5f420c09cd4845e1b0d9498254749828
Source dataset
uspto-grants-2010_07
Patent number
US07759337B2

Reaction notes

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