Sodium Carbonate → 2-{4-[6-(6-Methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinolin-3-yl]pyrazol-1-yl}-ethanol

HRID 655288Notes

Reaction equation

HRID 655288 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.C([O-])(=O)C.[K+].Br[C:29]1[CH:30]=[N:31][N:32]([CH2:34][CH2:35][OH:36])[CH:33]=1.C(=O)([O-])[O-].[Na+].[Na+].[O-]S([O-])(=O)=O.[Na+].[Na+]>CC(N(C)C)=O.C(#N)C.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]>[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:29]3[CH:30]=[N:31][N:32]([CH2:34][CH2:35][OH:36])[CH:33]=3)=[CH:11]4)=[N:14][N:15]=2)[N:18]=1

Participants

9

Reactant 5

HCID 10340Sodium CarbonateHCID 24436Sodium SulfateHCID 517044Potassium AcetateHCID 166406422-(4-Bromo-1H-pyrazol-1-yl)ethanolHCID 593202953-Bromo-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinoline

Product 1

HCID 593203652-{4-[6-(6-Methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinolin-3-yl]pyrazol-1-yl}-ethanol

Reagents, catalysts & solvents 3

HCID 53485975CID 53485975CatalystHCID 6342AcetonitrileSolventHCID 31374DimethylacetamideSolvent2×

Procedure

To a microwave vessel was added 3-bromo-6-(6-methyl-[1,2,4]triazolo[4,3-b]pyridazin-3-ylmethyl)-quinoline (80 mg, 0.23 mmol, 1 equiv), bis(pinacol)borane (69 mg, 0.27 mmol, 1.2 equiv), potassium acetate (66 mg, 0.67 mmol, 3.0 equiv) followed by dimethylacetamide (0.8 mL). The solution was degassed for 10 min and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (7 mg, 0.01 mmol, 0.048 equiv added. The microwave vessel was capped and reacted in a microwave reactor at 120° C. for 1 hour. The microwave vessel was cooled and then 2-(4-bromo-pyrazol-1-yl)-ethanol (0.18 mmol, 0.8 equiv) dissolved in dimethylacetamide (0.6 mL) was added, followed by 2 M aqueous sodium carbonate (0.6 mL). The solution was degassed for 10 min and dichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (7 mg, 0.01 mmol, 0.048 equiv) added. The microwave vessel was capped and reacted in a microwave reactor at 120° C. for 2 hours. After cooling, Na2SO4 (3 g) was added and the mixture diluted with acetonitrile and filtered through a pad of celite. The filtrate was concentrated onto silica gel and purified by either flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-80:20) or preparative HPLC to return the title compound. Analytical data presented in Table 2.

Workup

  1. customThe solution was degassed for 10 min
  2. additiondichloro[1,1′-bis(diphenylphosphino)ferrocene]palladium(II) dichloromethane adduct (7 mg, 0.01 mmol, 0.048 equiv added
  3. customThe microwave vessel was capped
  4. customreacted in a microwave reactor at 120° C. for 1 hour
  5. temperatureThe microwave vessel was cooled
  6. additionwas added
  7. customThe solution was degassed for 10 min
  8. customThe microwave vessel was capped
  9. customreacted in a microwave reactor at 120° C. for 2 hours
  10. temperatureAfter cooling
  11. filtrationfiltered through a pad of celite
  12. concentrationThe filtrate was concentrated onto silica gel
  13. custompurified by either flash chromatography (SiO2, CH2Cl2:CH3OH 100:0-80:20) or preparative HPLC

Sources & evidence

ORD record
ord-d45770956ff34193b9cb446b1c469b32
Source dataset
uspto-grants-2011_12
Patent number
US08071581B2

Reaction notes

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