Dichloromethane → HCID 178487940, compound

HRID 245745

Reaction equation

HRID 245745 reaction equation
Br[C:2]1[N:3]=[C:4]([C@H:12]2[CH2:17][CH2:16][C@H:15]([N:18]3[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]3)[CH2:14][CH2:13]2)[N:5]2[CH:10]=[CH:9][N:8]=[C:7]([CH3:11])[C:6]=12.[CH3:25][O:26][C:27]1[CH:33]=[C:32](B2OC(C)(C)C(C)(C)O2)[CH:31]=[CH:30][C:28]=1[NH2:29].C(=O)([O-])[O-].[K+].[K+].ClCCl>O1CCOCC1.C(#N)C>[CH3:25][O:26][C:27]1[CH:33]=[C:32]([C:2]2[N:3]=[C:4]([C@H:12]3[CH2:17][CH2:16][C@H:15]([N:18]4[CH2:23][CH2:22][N:21]([CH3:24])[CH2:20][CH2:19]4)[CH2:14][CH2:13]3)[N:5]3[CH:10]=[CH:9][N:8]=[C:7]([CH3:11])[C:6]=23)[CH:31]=[CH:30][C:28]=1[NH2:29]

Participants

7

Reactant 4

HCID 6344DichloromethaneHCID 11430Potassium CarbonateHCID 177502072-Methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 178432912HCID 178432912, compound

Product 1

HCID 178487940HCID 178487940, compoundYield 37.1%

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
89 °C

Procedure

To a suspension of 1-bromo-8-methyl-3-((trans)-4-(4-methylpiperazin-1-yl)cyclohexyl)imidazo[1,5-a]pyrazine (0.714 mmol, 280 mg) and 2-methoxy-4-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)aniline (0.714 mmol, 178 mg) in dioxane (5 mL) was added aqueous 2M potassium carbonate (3.57 mmol, 1.78 mL). The mixture was degassed and put under a nitrogen atmosphere. Then 1,1′-bis(diphenylphosphino)ferrocene palladium (II) chloride complex with dichloromethane (0.050 mmol, 40.4 mg) was added and the reaction mixture was heated to 89° C. After three hours the reaction mixture was diluted with acetonitrile (9 ml) and filtered over decalite. The filtrate was concentrated in vacuo and the residue was purified by column chromatography (silica gel; gradient of dichloromethane to dichloromethane/methanol 5/1) to give 2-methoxy-4-(8-methyl-3-((trans)-4-(4-methylpiperazin-1-yl)cyclohexyl)imidazo[1,5-a]pyrazin-1-yl)aniline (115 mg).

Workup

  1. customThe mixture was degassed
  2. filtrationfiltered over decalite
  3. concentrationThe filtrate was concentrated in vacuo
  4. customthe residue was purified by column chromatography (silica gel; gradient of dichloromethane to dichloromethane/methanol 5/1)

Sources & evidence

ORD record
ord-13660ae0602c4d3fa3e8d6f6075710bc
Source dataset
uspto-grants-2014_02
Patent number
US08658794B2

Linked notes

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