3-chloro-4,5-dimethyl-6-((R)-3-methyl-piperazin-1-yl)-pyridazine → (R)-3-Benzyl-4,5-dimethyl-6-(3-methylpiperazin-1-yl)pyridazine

HRID 447109Notes

Reaction equation

HRID 447109 reaction equation
Cl[C:2]1[N:3]=[N:4][C:5]([N:10]2[CH2:15][CH2:14][NH:13][C@H:12]([CH3:16])[CH2:11]2)=[C:6]([CH3:9])[C:7]=1[CH3:8].[Br-].[CH2:18]([Zn+])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1>C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH2:18]([C:2]1[N:3]=[N:4][C:5]([N:10]2[CH2:15][CH2:14][NH:13][C@H:12]([CH3:16])[CH2:11]2)=[C:6]([CH3:9])[C:7]=1[CH3:8])[C:19]1[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=1

Participants

4

Reactant 2

HCID 591915183-chloro-4,5-dimethyl-6-((R)-3-methyl-piperazin-1-yl)-pyridazineHCID 178419772HCID 178419772, compound

Product 1

HCID 59191647(R)-3-Benzyl-4,5-dimethyl-6-(3-methylpiperazin-1-yl)pyridazineYield 66%

Reagents, catalysts & solvents 1

HCID 178418397HCID 178418397, compoundCatalyst

Procedure

3-Chloro-4,5-dimethyl-6-((R)-3-methyl-piperazin-1-yl)-pyridazine (400 mg, 1.66 mmol, 1 eq) is added to a solution of benzylzinc bromide (12.3 mL 0.5 M in THF, 6.64 mmol, 4 eq) and tetrakis(triphenylphosphine)palladium (100 mg, 0.08 mmol, 0.05 eq) in a microwave vial. The vial is sealed and irradiated in the microwave at 100° C. (high absorption setting) for 40 min. The reaction mixture is concentrated and purified by silica gel chromatography (5-20% EtOAc/heptane) to yield the desired compound (324 mg, 66%).

Workup

  1. customThe vial is sealed
  2. customirradiated in the microwave at 100° C. (high absorption setting) for 40 min
  3. concentrationThe reaction mixture is concentrated
  4. custompurified by silica gel chromatography (5-20% EtOAc/heptane)

Sources & evidence

ORD record
ord-ddf531f1d75847bcbde1c349989ce794
Source dataset
uspto-grants-2013_07
Patent number
US08481542B2

Reaction notes

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