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

HRID 1798484Notes

Reaction equation

HRID 1798484 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C:8]([C:10]2[CH:15]=[CH:14][C:13](B3OC(C)(C)C(C)(C)O3)=[CH:12][CH:11]=2)=[O:9])[CH2:4][CH2:3]1.C([O-])([O-])=O.[Na+].[Na+].Br[C:32]1[CH:33]=[C:34]([C:38]2[CH:43]=[C:42]([NH:44][CH3:45])[N:41]=[C:40]([C:46]3[CH:51]=[CH:50][CH:49]=[CH:48][N:47]=3)[CH:39]=2)[CH:35]=[N:36][CH:37]=1>COCCOC.C(Cl)Cl.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.C1C=CC(P(C2C=CC=CC=2)[C-]2C=CC=C2)=CC=1.Cl[Pd]Cl.[Fe+2]>[CH3:45][NH:44][C:42]1[N:41]=[C:40]([C:46]2[CH:51]=[CH:50][CH:49]=[CH:48][N:47]=2)[CH:39]=[C:38]([C:34]2[CH:35]=[N:36][CH:37]=[C:32]([C:13]3[CH:12]=[CH:11][C:10]([C:8]([N:5]4[CH2:4][CH2:3][N:2]([CH3:1])[CH2:7][CH2:6]4)=[O:9])=[CH:15][CH:14]=3)[CH:33]=2)[CH:43]=1

Participants

7

Reactant 3

HCID 10340Sodium CarbonateHCID 27600304-(4-Methylpiperazine-1-carbonyl)phenylboronic acid pinacol esterHCID 86633643(5''-Bromo-[2,2';4',3'']terpyridin-6'-yl)-methyl-amine

Product 1

HCID 44136079[4-(6'-Methylamino-[2,2';4',3'']terpyridin-5''-yl)-phenyl]-(4-methyl-piperazin-1-yl)-methanone

Reagents, catalysts & solvents 3

HCID 178418228Bis(cyclopenta-1,4-dien-1-yl(diphenyl)phosphane);dichloropalladium;iron(2+)CatalystHCID 6344DichloromethaneSolvent2×HCID 80711,2-DimethoxyethaneSolvent

Procedure

To a solution of (4-Methyl-piperazin-1-yl)-[4-(4,4,5,5-tetramethyl-[1,3,2]dioxaborolan-2-yl)-phenyl]-methanone (1.2 eq, 1.55 mmol, 0.511 g) and 2M Na2CO3 (2.0 eq, 2.58 mmol, 1.3 ml) in DME (10 ml) is added (5″-Bromo-[2,2′;4′,3″]terpyridin-6′-yl)-methyl-amine (1 eq, 1.29 mmol, 0.44 g) followed by [1,1′-Bis(diphenylphosphino)-ferrocene]dichloropalladium (II), complex with DCM (0.1 eq, 0.128 mmol, 0.094 g). The reaction mixture is heated using microwave radiation at 90° C. for 90 mins. 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 crude 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]+ 465.

Workup

  1. temperatureThe reaction mixture is heated
  2. customat 90° C.
  3. customfor 90 mins
  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, 0-20% 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-af65842002b248168b039f4d69bf868d
Source dataset
uspto-grants-2013_01
Patent number
US08343966B2

Reaction notes

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