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

HRID 1479989Notes

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-7db3c571c4aa48af971b235a0e5e30e4
Source dataset: uspto-grants-2016_08
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US09409871B2

Reaction notes

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