Triethylamine → Methyl-[5''-(3-methyl-3H-imidazol-4-ylethynyl)-[2,2';4',3'']terpyridin-6'-yl]-amine

HRID 1798541Notes

Reaction equation

HRID 1798541 reaction equation
Br[C:2]1[CH:3]=[C:4]([C:8]2[CH:13]=[C:12]([NH:14][CH3:15])[N:11]=[C:10]([C:16]3[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=3)[CH:9]=2)[CH:5]=[N:6][CH:7]=1.C(=O)([O-])[O-].[K+].[K+].C(N(CC)CC)C.[CH3:35][N:36]1[C:40]([C:41]#[C:42][Si](C)(C)C)=[CH:39][N:38]=[CH:37]1>COCCOC.CCOC(C)=O.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.[Cu]I>[CH3:15][NH:14][C:12]1[N:11]=[C:10]([C:16]2[CH:21]=[CH:20][CH:19]=[CH:18][N:17]=2)[CH:9]=[C:8]([C:4]2[CH:5]=[N:6][CH:7]=[C:2]([C:42]#[C:41][C:40]3[N:36]([CH3:35])[CH:37]=[N:38][CH:39]=3)[CH:3]=2)[CH:13]=1

Participants

9

Reactant 4

HCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 44316295-[(Trimethylsilyl)ethynyl])-1-methylimidazoleHCID 86633643(5''-Bromo-[2,2';4',3'']terpyridin-6'-yl)-methyl-amine

Product 1

HCID 86633650Methyl-[5''-(3-methyl-3H-imidazol-4-ylethynyl)-[2,2';4',3'']terpyridin-6'-yl]-amine

Reagents, catalysts & solvents 4

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 80711,2-DimethoxyethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of (5″-Bromo-[2,2′;4′,3″]terpyridin-6′-yl)-methyl-amine (Example 2.1, step1) (1 eq, 0.147 mmol, 0.050 g) in DME (1 ml) is added potassium carbonate (1 eq, 0.147 mmol, 0.020 g), tetrakis(triphenylphosphine)palladium(0) (0.1 eq, 0.015 mmol, 17 mg), triethylamine (2 eq, 0.293 mmol, 0.041 ml) and 1-methyl-5-((trimethylsilyl)ethynyl)-1H-imidazole (1 eq, 0.147 mmol, 26.1 mg), followed by Copper (I) iodide (0.5 eq, 0.073 mmol, 14 mg). The reaction mixture is heated using microwave radiation at 70° C. for 2 hrs. The reaction mixture is dissolved in EtOAc and washed with water. The organic layer is washed with brine, dried over drying agent MgSO4, filtered and the organic solvent is reduced in vacuo. The crude residue is purified by reverse phase column chromatography (Isolute™ C18, 0-50% acetonitrile in water—0.1% TFA). The appropriate fractions by HPLC are combined and concentrated in vacuo. The resulting residue is dissolved in MeOH and loaded onto a SCX-2 cartridge eluting with MeOH followed by 2M NH3 in MeOH. The methanolic ammonia fractions are combined, concentrated in vacuo and dried under vacuum to afford the title compound; [M+H]+ 367.

Workup

  1. temperatureThe reaction mixture is heated
  2. customat 70° C.
  3. customfor 2 hrs
  4. washwashed with water
  5. washThe organic layer is washed with brine
  6. customdried
  7. dry with materialover drying agent MgSO4
  8. filtrationfiltered
  9. customThe crude residue is purified by reverse phase column chromatography (Isolute™ C18, 0-50% acetonitrile in water—0.1% TFA)
  10. concentrationconcentrated in vacuo
  11. dissolutionThe resulting residue is dissolved in MeOH
  12. washeluting with MeOH
  13. concentrationconcentrated in vacuo
  14. customdried under vacuum

Sources & evidence

ORD record
ord-975ded68a80a4243a04b9fcf6d930ee8
Source dataset
uspto-grants-2013_01
Patent number
US08343966B2

Reaction notes

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