Cesium carbonate → 6-Chloro-N-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amine

HRID 1024023Notes

Reaction equation

HRID 1024023 reaction equation
Br[C:2]1[C:3]2[N:4]([CH:9]=[CH:10][N:11]=2)[N:5]=[C:6]([Cl:8])[CH:7]=1.[CH3:12][N:13]1[CH2:18][CH2:17][N:16]([C:19]2[CH:20]=[CH:21][C:22]([NH2:25])=[N:23][CH:24]=2)[CH2:15][CH2:14]1.CC1(C)C2C(=C(P(C3C=CC=CC=3)C3C=CC=CC=3)C=CC=2)OC2C(P(C3C=CC=CC=3)C3C=CC=CC=3)=CC=CC1=2.C([O-])([O-])=O.[Cs+].[Cs+]>C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.C1C=CC(/C=C/C(/C=C/C2C=CC=CC=2)=O)=CC=1.[Pd].[Pd].O1CCOCC1>[Cl:8][C:6]1[CH:7]=[C:2]([NH:25][C:22]2[CH:21]=[CH:20][C:19]([N:16]3[CH2:17][CH2:18][N:13]([CH3:12])[CH2:14][CH2:15]3)=[CH:24][N:23]=2)[C:3]2[N:4]([CH:9]=[CH:10][N:11]=2)[N:5]=1

Participants

7

Reactant 4

HCID 10796Cesium carbonateHCID 6360441,1'-(9,9-Dimethyl-9H-xanthene-4,5-diyl)bis(1,1-diphenylphosphine)HCID 223298335-(4-Methylpiperazin-1-yl)pyridin-2-amineHCID 468352698-Bromo-6-chloroimidazo(1,2-b)pyridazine

Product 1

HCID 866841236-Chloro-N-(5-(4-methylpiperazin-1-yl)pyridin-2-yl)imidazo[1,2-b]pyridazin-8-amineYield 101.8%

Reagents, catalysts & solvents 2

HCID 9811564Bis(dibenzylideneacetone)palladiumCatalystHCID 312751,4-DioxaneSolvent

Procedure

A 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser was charged with 104a (2.0 g, 4 mmol), 5-(4-methylpiperazin-1-yl)pyridin-2-amine (920 mg, 4.8 mmol), tris(dibenzylideneacetone)dipalladium(0) (366 mg, 0.4 mmol), XantPhos (688 mg, 1.2 mmol), Cs2CO3 (2.6 g, 8.0 mmol), and 1,4-dioxane (60 mL). After three cycles of vacuum/argon flush, the mixture was heated at reflux for 15 h. It was then cooled to room temperature and filtered. The filtrate was concentrated under reduced pressure and the resulting residue was purified by silica-gel column chromatography eluting with dichloromethane/methanol (20:1) to afford 104b as yellow solid (1.4 g, 70%). MS: [M+H]+344.

Workup

  1. customA 100-mL single-neck round-bottomed flask equipped with a magnetic stirrer and a reflux condenser
  2. customAfter three cycles of vacuum/argon flush
  3. temperaturethe mixture was heated
  4. temperatureat reflux for 15 h
  5. filtrationfiltered
  6. concentrationThe filtrate was concentrated under reduced pressure
  7. customthe resulting residue was purified by silica-gel column chromatography
  8. washeluting with dichloromethane/methanol (20:1)

Sources & evidence

ORD record
ord-6ba5bdaba53545c486872e28b1f3bfd4
Source dataset
uspto-grants-2014_05
Patent number
US08722676B2

Reaction notes

Loading…