Potassium Carbonate → Methyl-{5''-[3-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-[2,2';4',3'']terpyridin-6'-yl}-amine

HRID 1798545Notes

Reaction equation

HRID 1798545 reaction equation
C(=O)([O-])[O-].[K+].[K+].[CH3:7][NH:8][C:9]1[N:14]=[C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)[CH:12]=[C:11]([C:21]2[CH:22]=[N:23][CH:24]=[C:25]([C:27]3[CH:28]=[C:29]([OH:33])[CH:30]=[CH:31][CH:32]=3)[CH:26]=2)[CH:10]=1.Cl[CH2:35][CH2:36][N:37]1[CH2:41][CH2:40][CH2:39][CH2:38]1>C(#N)C.C(Cl)Cl>[CH3:7][NH:8][C:9]1[N:14]=[C:13]([C:15]2[CH:20]=[CH:19][CH:18]=[CH:17][N:16]=2)[CH:12]=[C:11]([C:21]2[CH:22]=[N:23][CH:24]=[C:25]([C:27]3[CH:32]=[CH:31][CH:30]=[C:29]([O:33][CH2:35][CH2:36][N:37]4[CH2:41][CH2:40][CH2:39][CH2:38]4)[CH:28]=3)[CH:26]=2)[CH:10]=1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 816691-(2-Chloroethyl)pyrrolidineHCID 687361943-(6'-Methylamino-[2,2';4',3'']terpyridin-5''-yl)-phenol

Product 1

HCID 68757059Methyl-{5''-[3-(2-pyrrolidin-1-yl-ethoxy)-phenyl]-[2,2';4',3'']terpyridin-6'-yl}-amine

Reagents, catalysts & solvents 2

HCID 6342AcetonitrileSolventHCID 6344DichloromethaneSolvent

Procedure

Potassium carbonate (3.0 eq, 0.686 mmol, 95 mg) is added to a suspension of 3-(6′-Methylamino-[2,2′;4′,3″]terpyridin-5″-yl)-phenol (Example 2.189, step 1) (1.0 eq, 0.229 mmol, 81 mg) in dry acetonitrile (2.0 ml) under an inert atmosphere of nitrogen. 1-(2-Chloro-ethyl)-pyrrolidine (3 eq, 0.686 mmol, 92 mg) is added and the reaction is heated using microwave radiation at 150° C. for 2 hours. The reaction mixture is dissolved in DCM 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 residue is purified by reverse phase column chromatography (Isolute™ C18, 0-40% 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]+ 453.

Workup

  1. temperaturethe reaction is heated
  2. customat 150° C.
  3. customfor 2 hours
  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 residue is purified by reverse phase column chromatography (Isolute™ C18, 0-40% 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-676c3b50b82342f7bad3f1323c0e27de
Source dataset
uspto-grants-2013_01
Patent number
US08343966B2

Reaction notes

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