Sodium Carbonate → 6-[(R)-4-(4-Benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitrile

HRID 42186

Reaction equation

HRID 42186 reaction equation
C([O-])([O-])=O.[Na+].[Na+].Cl[C:8]1[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[CH:10][N:9]=1.[CH2:16]([C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]([N:33]2[CH2:38][CH2:37][NH:36][C@H:35]([CH3:39])[CH2:34]2)=[N:25][N:24]=1)[C:17]1[CH:22]=[CH:21][CH:20]=[CH:19][CH:18]=1>CN(C=O)C.O1CCOCC1>[CH2:16]([C:23]1[C:32]2[C:27](=[CH:28][CH:29]=[CH:30][CH:31]=2)[C:26]([N:33]2[CH2:38][CH2:37][N:36]([C:8]3[CH:15]=[CH:14][C:11]([C:12]#[N:13])=[CH:10][N:9]=3)[C@H:35]([CH3:39])[CH2:34]2)=[N:25][N:24]=1)[C:17]1[CH:18]=[CH:19][CH:20]=[CH:21][CH:22]=1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 51520946-Chloro-3-pyridinecarbonitrileHCID 441862481-Benzyl-4-((R)-3-methyl-piperazin-1-yl)-phthalazine

Product 1

HCID 441864806-[(R)-4-(4-Benzylphthalazin-1-yl)-2-methylpiperazin-1-yl]nicotinonitrileYield 42.2%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 312751,4-DioxaneSolvent

Procedure

Solid Na2CO3 (50 mg, 0.47 mmol, 1.5 eq) is added to a solution of 6-chloronicotinonitrile (50 mg, 0.36 mmol, 1.2 eq), 1-benzyl-4-((R)-3-methyl-piperazin-1-yl)-phthalazine (100 mg, 0.31 mmol, 1.0 eq) in DMF (1 mL) and dioxane (2 mL) in a microwave vial. The vial is sealed and irradiated in the microwave at 180° C. (high absorption setting) for 30 minutes. The reaction mixture is concentrated, dichloromethane is added and is washed with water then brine. The organic fraction is dried over sodium sulfate, and is evaporated under reduced pressure, then purified by flash chromatography (50%-90% EtOAc/Hexane) to afford the title compound as a white solid (55 mg, 42% yield).

Workup

  1. customThe vial is sealed
  2. customirradiated in the microwave at 180° C. (high absorption setting) for 30 minutes
  3. concentrationThe reaction mixture is concentrated
  4. additiondichloromethane is added
  5. washis washed with water
  6. dry with materialThe organic fraction is dried over sodium sulfate
  7. customis evaporated under reduced pressure
  8. custompurified by flash chromatography (50%-90% EtOAc/Hexane)

Sources & evidence

ORD record
ord-0ba5931c41c24e159e704285350d2dc6
Source dataset
uspto-grants-2013_09
Patent number
US08536168B2

Linked notes

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