6-Amino-3-chloropyridazine → 3-Pyridazinamine, 6-(4-methyl-1-piperazinyl)-

HRID 449658Notes

Reaction equation

HRID 449658 reaction equation
Cl[C:2]1[N:7]=[N:6][C:5]([NH2:8])=[CH:4][CH:3]=1.[CH3:9][N:10]1[CH2:15][CH2:14][NH:13][CH2:12][CH2:11]1>>[CH3:9][N:10]1[CH2:15][CH2:14][N:13]([C:2]2[N:7]=[N:6][C:5]([NH2:8])=[CH:4][CH:3]=2)[CH2:12][CH2:11]1

Participants

3

Reactant 2

HCID 216436-Amino-3-chloropyridazineHCID 531671-Methylpiperazine

Product 1

HCID 203168163-Pyridazinamine, 6-(4-methyl-1-piperazinyl)-Yield 24.5%

Conditions

Temperature
165 °C

Procedure

6-Chloro-pyridazin-3-ylamine (2.0 g, 15.4 mmol, Eq: 1.00) was dissolved in 1-methylpiperazine (15.5 g, 154 mmol, Eq: 10.0) and heated in a sand bath at 165° C. for 4 hours. The reaction mixture was then heated at 200° C. for 2 hours in a microwave reactor. The crude product was purified by chromatography using 10% methanol (with approximately 2% ammonium hydroxide) in DCM. To the still impure product was added aqueous sodium bicarbonate and DCM and the layers were separated. The aqueous layer was back extracted twice with DCM. The combined organic layers were concentrated, triturated with isopropyl acetate, filtered and dried to give 730 mg (24.5%) of a yellow solid.

Workup

  1. temperatureThe reaction mixture was then heated at 200° C. for 2 hours in a microwave reactor
  2. customThe crude product was purified by chromatography
  3. additionTo the still impure product was added aqueous sodium bicarbonate and DCM
  4. customthe layers were separated
  5. extractionThe aqueous layer was back extracted twice with DCM
  6. concentrationThe combined organic layers were concentrated
  7. customtriturated with isopropyl acetate
  8. filtrationfiltered
  9. customdried

Sources & evidence

ORD record
ord-c3f07f18c40841b2b0f1846673a9cea4
Source dataset
uspto-grants-2013_07
Patent number
US08481540B2

Reaction notes

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