Ethyl Acetate → HCID 57917251, compound

HRID 69305Notes

Reaction equation

HRID 69305 reaction equation
Cl[C:2]1[CH:3]=[CH:4][C:5]2[N:6]([C:8]([CH:11]([C:13]3[CH:14]=[CH:15][C:16]4[N:17]([CH:19]=[CH:20][N:21]=4)[CH:18]=3)[CH3:12])=[CH:9][N:10]=2)[N:7]=1.[C:22]1([CH3:31])[CH:27]=[CH:26][CH:25]=[C:24](B(O)O)[CH:23]=1.C([O-])([O-])=O.[Na+].[Na+].CCOC(C)=O>COCCOC.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[N:21]1[CH:20]=[CH:19][N:17]2[CH:18]=[C:13]([CH:11]([C:8]3[N:6]4[N:7]=[C:2]([C:24]5[CH:23]=[C:22]([CH3:31])[CH:27]=[CH:26][CH:25]=5)[CH:3]=[CH:4][C:5]4=[N:10][CH:9]=3)[CH3:12])[CH:14]=[CH:15][C:16]=12

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 27339503-Tolylboronic acidHCID 57917275(Rac)-6-chloro-3-(1-imidazo[1,2-a]pyridin-6-yl-ethyl)-imidazo[1,2-b]pyridazine

Product 1

HCID 57917251HCID 57917251, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
150 °C

Procedure

(rac)-6-Chloro-3-(1-imidazo[1,2-a]pyridin-6-yl-ethyl)-imidazo[1,2-b]pyridazine (Example 292, 200 mg, 0.672 mmol) was dissolved in DME (3.36 mL) with 3-tolylboronic acid (91 mg, 0.672 mmol), 2 M Na2CO3 solution (1.21 mL, 2.418 mmol) and tetrakis(triphenylphosphine)palladium (38.8 mg, 0.034 mmol). The RM was heated at 150° C. 5 min under microwave irradiations. It was taken up with EtOAc and washed with 10% Na2CO3 solution and brine. Then it was dried over Na2SO4, filtered and concentrated. The residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, 0 to 20% MeOH in DCM). Combined fractions were concentrated. The white solid obtained was a repurified by preparative HPLC with acetonitrile and water (+0.1% TFA). The fractions were joined and were lyophilized. The residue was dissolved in MeOH and it was passed through an SPE cartridge of HCO3− to remove the TFA salt. The filtrate was evaporated to give the free salt of the title compound as a white solid (tR 0.9 min (conditions 2), MH+=354).

Workup

  1. custom5 min
  2. washwashed with 10% Na2CO3 solution and brine
  3. dry with materialThen it was dried over Na2SO4
  4. filtrationfiltered
  5. concentrationconcentrated
  6. customThe residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, 0 to 20% MeOH in DCM)
  7. concentrationCombined fractions were concentrated
  8. customThe white solid obtained
  9. customa repurified by preparative HPLC with acetonitrile and water (+0.1% TFA)
  10. dissolutionThe residue was dissolved in MeOH
  11. customto remove the TFA salt
  12. customThe filtrate was evaporated

Sources & evidence

ORD record
ord-e4c4beaf3ed64d64a6628ae40fdec07d
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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