Ethyl Acetate → HCID 57917397, compound

HRID 69303Notes

Reaction equation

HRID 69303 reaction equation
Br[C:2]1[N:6]2[CH:7]=[C:8]([CH2:11][C:12]3[N:16]4[N:17]=[C:18]([C:21]5[CH:22]=[N:23][N:24]([CH3:26])[CH:25]=5)[CH:19]=[CH:20][C:15]4=[N:14][CH:13]=3)[CH:9]=[CH:10][C:5]2=[N:4][CH:3]=1.[N:27]1[CH:32]=[CH:31][CH:30]=[C:29](B(O)O)[CH:28]=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>[CH3:26][N:24]1[CH:25]=[C:21]([C:18]2[CH:19]=[CH:20][C:15]3[N:16]([C:12]([CH2:11][C:8]4[CH:9]=[CH:10][C:5]5[N:6]([C:2]([C:29]6[CH:28]=[N:27][CH:32]=[CH:31][CH:30]=6)=[CH:3][N:4]=5)[CH:7]=4)=[CH:13][N:14]=3)[N:17]=2)[CH:22]=[N:23]1

Participants

7

Reactant 4

HCID 8857Ethyl AcetateHCID 10340Sodium CarbonateHCID 27343783-Pyridinylboronic acidHCID 57917273HCID 57917273, compound

Product 1

HCID 57917397HCID 57917397, compound

Reagents, catalysts & solvents 2

HCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolvent

Conditions

Temperature
150 °C

Procedure

3-(3-Bromo-imidazo[1,2-a]pyridin-6-ylmethyl)-6-(1-methyl-1H-pyrazol-4-yl)-imidazo[1,2-b]pyridazine (Example 296, 80 mg, 0.196 mmol) was dissolved in DME (0.653 mL) with pyridin-3-ylboronic acid (24.1 mg, 0.196 mmol), 2 M Na2CO3 solution (0.353 mL, 0.705 mmol) and tetrakis(triphenylphosphine)palladium (11.3 mg, 0.010 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 dissolved in MeOH and passed through an SPE cartridge of PL-Thiol MP to remove the palladium. Then the filtrate was purified 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 0.6 min (conditions 2), MH+=407).

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. dissolutionThe residue was dissolved in MeOH
  7. customto remove the palladium
  8. customThen the filtrate was purified by preparative HPLC with acetonitrile and water (+0.1% TFA)
  9. dissolutionThe residue was dissolved in MeOH
  10. customto remove the TFA salt
  11. customThe filtrate was evaporated

Sources & evidence

ORD record
ord-abd6a07561b244868ddc60d6dea32a61
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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