Sodium Carbonate → [4-(6'-Cyclopropylamino-[2,2';4',3'']terpyridin-5''-yl)-phenyl]-piperazin-1-yl-methanone

HRID 1798486Notes

Reaction equation

HRID 1798486 reaction equation
[N:1]1([C:7]([C:9]2[CH:14]=[CH:13][C:12](B3OC(C)(C)C(C)(C)O3)=[CH:11][CH:10]=2)=[O:8])[CH2:6][CH2:5][NH:4][CH2:3][CH2:2]1.C([O-])([O-])=O.[Na+].[Na+].Br[C:31]1[CH:32]=[C:33]([C:37]2[CH:42]=[C:41]([NH:43][CH:44]3[CH2:46][CH2:45]3)[N:40]=[C:39]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][N:48]=3)[CH:38]=2)[CH:34]=[N:35][CH:36]=1>COCCOC.C(Cl)Cl>[CH:44]1([NH:43][C:41]2[N:40]=[C:39]([C:47]3[CH:52]=[CH:51][CH:50]=[CH:49][N:48]=3)[CH:38]=[C:37]([C:33]3[CH:34]=[N:35][CH:36]=[C:31]([C:12]4[CH:11]=[CH:10][C:9]([C:7]([N:1]5[CH2:2][CH2:3][NH:4][CH2:5][CH2:6]5)=[O:8])=[CH:14][CH:13]=4)[CH:32]=3)[CH:42]=2)[CH2:46][CH2:45]1

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 177499131-(4-(Tetramethyl-1,3,2-dioxaborolan-2-yl)benzoyl)piperazineHCID 44135953(5''-Bromo-[2,2';4',3'']terpyridin-6'-yl)-cyclopropyl-amine

Product 1

HCID 44136608[4-(6'-Cyclopropylamino-[2,2';4',3'']terpyridin-5''-yl)-phenyl]-piperazin-1-yl-methanone

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of piperazin-1-yl-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-methanone (1.2 eq, 0.163 mmol, 0.052 g) in dry DME (1 ml) under an inert atmosphere of argon is added 2M Na2CO3 (3 eq, 0.408 mmol, 0.2 ml) followed by (5″-Bromo-[2,2′;4′,3″]terpyridin-6′-yl)-cyclopropyl-amine (Example 1.26) (1 eq, 0.136 mmol, 0.050 g) and PdCl2dppf (0.1 eq, 0.0136 mmol, 0.001 g). The reaction mixture is heated using microwave radiation at 90° C. for 2 hours 30. The reaction mixture is dissolved in DCM and washed with water. The organic layer is 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, 0-40% 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 and 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]+ 477.

Workup

  1. temperatureThe reaction mixture is heated
  2. customat 90° C.
  3. customfor 2 hours
  4. washwashed with water
  5. customThe organic layer is dried
  6. dry with materialover drying agent MgSO4
  7. filtrationfiltered
  8. customThe crude residue is purified by reverse phase column chromatography (Isolute™ C18, 0-40% acetonitrile in water—0.1% TFA)
  9. concentrationconcentrated in vacuo
  10. dissolutionThe resulting residue is dissolved in MeOH
  11. washeluting with MeOH
  12. concentrationconcentrated in vacuo
  13. customdried under vacuum

Sources & evidence

ORD record
ord-48063c90532a431a8deabba5b9e16b5e
Source dataset
uspto-grants-2013_01
Patent number
US08343966B2

Reaction notes

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