Potassium Carbonate → 6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-3-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazol-4-yl]-quinoline

HRID 655292

Reaction equation

HRID 655292 reaction equation
Br[C:2]1[CH:3]=[N:4][C:5]2[C:10]([CH:11]=1)=[CH:9][C:8]([CH2:12][C:13]1[N:17]3[N:18]=[C:19]([CH3:22])[CH:20]=[CH:21][C:16]3=[N:15][N:14]=1)=[CH:7][CH:6]=2.CC1(C)C(C)(C)OB([C:31]2[CH:32]=[N:33][N:34]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[CH:35]=2)O1.C([O-])([O-])=O.[K+].[K+].O1CCOCC1>C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C1C=CC([PH+]([C]2[CH][CH][CH][CH]2)C2C=CC=CC=2)=CC=1.C(Cl)Cl.Cl[Pd]Cl.[Fe].O.ClCCl>[CH3:22][C:19]1[CH:20]=[CH:21][C:16]2[N:17]([C:13]([CH2:12][C:8]3[CH:9]=[C:10]4[C:5](=[CH:6][CH:7]=3)[N:4]=[CH:3][C:2]([C:31]3[CH:32]=[N:33][N:34]([CH2:36][O:37][CH2:38][CH2:39][Si:40]([CH3:43])([CH3:42])[CH3:41])[CH:35]=3)=[CH:11]4)=[N:14][N:15]=2)[N:18]=1

Participants

8

Reactant 4

HCID 11430Potassium CarbonateHCID 312751,4-DioxaneHCID 574776664-(4,4,5,5-Tetramethyl-1,3,2-dioxaborolan-2-yl)-1-((2-(trimethylsilyl)ethoxy)methyl)-1H-pyrazoleHCID 593202953-Bromo-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinoline

Product 1

HCID 687027706-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-3-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazol-4-yl]-quinolineYield 80.3%

Reagents, catalysts & solvents 3

HCID 53485975CID 53485975CatalystHCID 962WaterSolvent2×HCID 6344DichloromethaneSolvent

Conditions

Temperature
130 °C

Procedure

To a microwave vial was added 3-bromo-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinoline (100 mg, 0.28 mmol, 1 equiv), 4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazole (113 mg, 0.35 mmol, 1.25 equiv), K2CO3 (78 mg, 0.566 mmol, 2.0 equiv) followed by 1,4-dioxane (3 mL) and water (1.5 mL). [0542] The solution was degassed with nitrogen for 10 min and then dichloro [1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (10 mg, 0.014 mmol, 0.05 equiv) was added. The microwave vessel was capped and heated in a microwave reactor at 130° C. for 30 min. The mixture was cooled and portioned between dichloromethane and water. The organic phase was absorbed onto silica gel and purified by flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-80:20) to give 6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-3-[1-(2-trimethylsilanyl-ethoxymethyl)-1H-pyrazol-4-yl]-quinoline (106 mg, 80% yield). The solid was then added to a 20% solution of ethylene diamine in dimethylformamide and stirred for 3 hours. The solvent was removed and the residue triterated with ethanol to afford the title compound (65 mg, 85% yield). Analytical data presented in Table 2.

Workup

  1. custom[0542] The solution was degassed with nitrogen for 10 min
  2. customThe microwave vessel was capped
  3. temperatureThe mixture was cooled
  4. customThe organic phase was absorbed onto silica gel
  5. custompurified by flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-80:20)

Sources & evidence

ORD record
ord-6fa9c9b587194e5db672d56c0eaf0762
Source dataset
uspto-grants-2011_12
Patent number
US08071581B2

Linked notes

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