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

HRID 447110Notes

Reaction equation

C([O-])([O-])=O.[K+].[K+].[CH3:7][C@@H:8]1[CH2:13][NH:12][CH2:11][CH2:10][NH:9]1.[Cl:14][C:15]1[N:16]=[N:17][C:18](Cl)=[C:19]([CH3:22])[C:20]=1[CH3:21]>CN(C=O)C>[Cl:14][C:15]1[N:16]=[N:17][C:18]([N:12]2[CH2:11][CH2:10][NH:9][C@H:8]([CH3:7])[CH2:13]2)=[C:19]([CH3:22])[C:20]=1[CH3:21]

Participants

Conditions

Temperature: 60 °C

Procedure

Solid K2CO3 (10 g, 72.4 mmol, 1.8 eq) is added to a solution of (R)-2-methyl-piperazine (4.00 g, 40 mmol, 1 eq) and 3,6-dichloro-4,5-dimethyl-pyridazine (8 g, 45.2 mml, 1.1 eq) in DMF (50 mL), and the resulting solution is stirred at 60° C. for 48 h. The reaction mixture is concentrated to ½ volume under reduced pressure and the minimum water (ca. 15 mL) required to dissolve the solid salts is added, followed by the addition of dichloromethane (100 mL). The organic layer is separated, dried over sodium sulfate and concentrated under reduced pressure, then purified by silica gel column chromatography (2%-20% MeOH/CH2Cl2) to yield the desired compound as a white solid (4.7 g, 49%).

Workup

concentrationThe reaction mixture is concentrated
dissolutionto dissolve the solid salts
additionis added
additionfollowed by the addition of dichloromethane (100 mL)
customThe organic layer is separated
dry with materialdried over sodium sulfate
concentrationconcentrated under reduced pressure
custompurified by silica gel column chromatography (2%-20% MeOH/CH2Cl2)

Sources & evidence

ORD record: ord-1e1fd29779414010b9756ef7af720ad0
Source dataset: uspto-grants-2013_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08481542B2

Reaction notes

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