Dimethylformamide → HCID 57917400, compound

HRID 69299Notes

Reaction equation

HRID 69299 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.[CH3:27][N:28]1C(=O)CCC1.C([Cu])#N.CN(C=O)C>O>[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:27]#[N:28])=[CH:3][N:4]=5)[CH:7]=4)=[CH:13][N:14]=3)[N:17]=2)[CH:22]=[N:23]1

Participants

6

Reactant 4

HCID 6228DimethylformamideHCID 13387N-methyl-2-pyrrolidoneHCID 57917273HCID 57917273, compoundHCID 178418546HCID 178418546, compound

Product 1

HCID 57917400HCID 57917400, compound

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
200 °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, 55 mg, 0.135 mmol) was introduced in a microwave reactor with NMP (150 μL) and CuCN (15.7 mg, 0.175 mmol). The RM was heated at 200° C. for 10+15 min. The black solid obtained was taken up with DMF. Water was added to the mixture and it was extracted with EtOAc/MeOH (9:1) twice. Combined organic layers was washed with 10% ammonia solution. The organic layer 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 0.8 min (conditions 2), MH+=355).

Workup

  1. customThe black solid obtained
  2. extractionwas extracted with EtOAc/MeOH (9:1) twice
  3. washCombined organic layers was washed with 10% ammonia solution
  4. dry with materialThe organic layer was dried over Na2SO4
  5. filtrationfiltered
  6. concentrationconcentrated
  7. customThe residue was purified by flash chromatography (CombiFlash® Companion System®, with RediSep® silica gel column, 0 to 20% MeOH in DCM)
  8. concentrationCombined fractions were concentrated
  9. customThe white solid obtained
  10. customa repurified by preparative HPLC with acetonitrile and water (+0.1% TFA)
  11. dissolutionThe residue was dissolved in MeOH
  12. customto remove the TFA salt
  13. customThe filtrate was evaporated

Sources & evidence

ORD record
ord-563e21b3e53241eb9740bfeeb5d214a0
Source dataset
uspto-grants-2014_09
Patent number
US08822468B2

Reaction notes

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