Isopropyl iodide → (5''-[1-(1-Isopropyl-piperidin-4-yl)-1H-pyrazol-4-yl]-[2,2';4',3'']terpyridin-6'-yl)-methyl-amine

HRID 1798537Notes

Reaction equation

HRID 1798537 reaction equation
[CH3:1][NH:2][C:3]1[N:8]=[C:7]([C:9]2[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=2)[CH:6]=[C:5]([C:15]2[CH:16]=[N:17][CH:18]=[C:19]([C:21]3[CH:22]=[N:23][N:24]([CH:26]4[CH2:31][CH2:30][NH:29][CH2:28][CH2:27]4)[CH:25]=3)[CH:20]=2)[CH:4]=1.I[CH:33]([CH3:35])[CH3:34]>CN(C=O)C.CCOC(C)=O>[CH:33]([N:29]1[CH2:30][CH2:31][CH:26]([N:24]2[CH:25]=[C:21]([C:19]3[CH:20]=[C:15]([C:5]4[CH:4]=[C:3]([NH:2][CH3:1])[N:8]=[C:7]([C:9]5[CH:14]=[CH:13][CH:12]=[CH:11][N:10]=5)[CH:6]=4)[CH:16]=[N:17][CH:18]=3)[CH:22]=[N:23]2)[CH2:27][CH2:28]1)([CH3:35])[CH3:34]

Participants

5

Reactant 2

HCID 6362Isopropyl iodideHCID 68757252Methyl-[5''-(1-piperidin-4-yl-1H-pyrazol-4-yl)-[2,2';4',3'']terpyridin-6'-yl]-amine

Product 1

HCID 86633647(5''-[1-(1-Isopropyl-piperidin-4-yl)-1H-pyrazol-4-yl]-[2,2';4',3'']terpyridin-6'-yl)-methyl-amine

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a solution of Methyl-[5″-(1-piperidin-4-yl-1H-pyrazol-4-yl)-[2,2′;4′,3″]terpyridin-6′-yl]-amine (Example 2.183) (1 eq, 0.122 mmol, 50 mg) in DMF (3 ml) cooled at 0° C. is added 2-iodopropane (7 eq, 0.854 mmol, 0.084 ml) and the reaction is stirred at room temperature for 5 hours. The reaction mixture is dissolved in EtOAc and washed with water. The combined organic extracts are washed with brine, dried over MgSO4 and concentrated in vacuo. The residue is purified by reverse phase column chromatography (Isolute™ C18, 0-20% 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]+ 454.

Workup

  1. washwashed with water
  2. washThe combined organic extracts are washed with brine
  3. dry with materialdried over MgSO4
  4. concentrationconcentrated in vacuo
  5. customThe residue is purified by reverse phase column chromatography (Isolute™ C18, 0-20% acetonitrile in water—0.1% TFA)
  6. concentrationconcentrated in vacuo
  7. dissolutionThe resulting residue is dissolved in MeOH
  8. washeluting with MeOH
  9. concentrationconcentrated in vacuo
  10. customdried under vacuum

Sources & evidence

ORD record
ord-2d491bfb3f004783bf378ec3c8ac9865
Source dataset
uspto-grants-2013_01
Patent number
US08343966B2

Reaction notes

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