3,6-Dichloropyridazine → 6-chloro-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine

HRID 1027143Notes

Reaction equation

HRID 1027143 reaction equation
[Cl:1][C:2]1[N:3]=[N:4][C:5](Cl)=[CH:6][CH:7]=1.[CH3:9][NH:10][CH:11]1[CH2:16][C:15]([CH3:18])([CH3:17])[NH:14][C:13]([CH3:20])([CH3:19])[CH2:12]1>C(O)CCC>[Cl:1][C:2]1[N:3]=[N:4][C:5]([N:10]([CH3:9])[CH:11]2[CH2:12][C:13]([CH3:19])([CH3:20])[NH:14][C:15]([CH3:18])([CH3:17])[CH2:16]2)=[CH:6][CH:7]=1

Participants

4

Reactant 2

HCID 673313,6-DichloropyridazineHCID 13657792N,2,2,6,6-Pentamethylpiperidin-4-amine

Product 1

HCID 867105396-chloro-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine

Reagents, catalysts & solvents 1

HCID 2631-ButanolSolvent

Conditions

Temperature
120 °C

Procedure

To 3,6-dichloropyridazine (4 g, 26.8 mmol) and N,2,2,6,6-pentamethylpiperidin-4-amine (7.32 g, 43.0 mmol) in a 300 mL round bottom flask was added butan-1-ol (67 mL) to give a colorless solution. The mixture was heated to 120° C. for 72 h. Butan-1-ol was removed using a rotary evaporator. The residue was partitioned between water and DCM, and the water layer was further extracted with DCM. The combined organic layers were washed with water and brine, dried over MgSO4, and concentrated in vacuo. The black crude material was stirred in small amount of EtOAc overnight, and the resulting off-white solid was collected to provide 6-chloro-N-methyl-N-(2,2,6,6-tetramethylpiperidin-4-yl)pyridazin-3-amine, Intermediate 1-1 (4.18 g, 14.78 mmol, 55.0% yield). LCMS Rt=0.8 min (condition B), MS (M+1)=283.5. 1H NMR (400 MHz, METHANOL-d4) δ ppm 7.40 (d, J=9.60 Hz, 1H), 7.14 (d, J=9.60 Hz, 1H), 4.96-5.13 (m, 1H), 2.93 (s, 3H), 1.59-1.68 (m, 2H), 1.51 (t, J=12.38 Hz, 2H), 1.20 (s, 6H), 1.33 (s, 6H).

Workup

  1. customto give a colorless solution
  2. customButan-1-ol was removed
  3. customa rotary evaporator
  4. customThe residue was partitioned between water and DCM
  5. extractionthe water layer was further extracted with DCM
  6. washThe combined organic layers were washed with water and brine
  7. dry with materialdried over MgSO4
  8. concentrationconcentrated in vacuo
  9. customthe resulting off-white solid was collected

Sources & evidence

ORD record
ord-e52cf1929b4148bf98a6aa728b81aadd
Source dataset
uspto-grants-2014_05
Patent number
US08729263B2

Reaction notes

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