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

HRID 1798492Notes

Reaction equation

HRID 1798492 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][C:44]([CH3:47])([CH3:46])[CH3:45])[N:40]=[C:39]([C:48]3[CH:53]=[CH:52][CH:51]=[CH:50][N:49]=3)[CH:38]=2)[CH:34]=[N:35][CH:36]=1>COCCOC.C(Cl)Cl>[C:44]([NH:43][C:41]1[N:40]=[C:39]([C:48]2[CH:53]=[CH:52][CH:51]=[CH:50][N:49]=2)[CH:38]=[C:37]([C:33]2[CH:34]=[N:35][CH:36]=[C:31]([C:12]3[CH:11]=[CH:10][C:9]([C:7]([N:1]4[CH2:2][CH2:3][NH:4][CH2:5][CH2:6]4)=[O:8])=[CH:14][CH:13]=3)[CH:32]=2)[CH:42]=1)([CH3:47])([CH3:45])[CH3:46]

Participants

6

Reactant 3

HCID 10340Sodium CarbonateHCID 177499131-(4-(Tetramethyl-1,3,2-dioxaborolan-2-yl)benzoyl)piperazineHCID 68737214(5''-Bromo-[2,2';4',3'']terpyridin-6'-yl)-tert-butyl-amine

Product 1

HCID 68762609[4-(6'-tert-Butylamino-[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, 0.25 mmol, 0.079 g) and 2M Na2CO3 (3 eq, 0.624 mmol, 0.3 ml) in dry DME (1.5 ml) are added (5″-Bromo-[2,2′;4′,3″]terpyridin-6′-yl)-tert-butyl-amine (Ex. 2.48; step 1) (1 eq, 0.208 mmol, 80 mg) and PdCl2dppf (0.1 eq, 0.0208 mmol, 15 mg). The reaction mixture is heated using microwave radiation at 90° C. for 1 hour. The reaction mixture is dissolved in DCM and washed with water. The organic solvent is reduced in vacuo and 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]+ 493.

Workup

  1. temperatureThe reaction mixture is heated
  2. customat 90° C.
  3. customfor 1 hour
  4. washwashed with water
  5. customthe residue is purified by reverse phase column chromatography (Isolute™ C18, 0-40% 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-232e0715e9004909b088742467731b0f
Source dataset
uspto-grants-2013_01
Patent number
US08343966B2

Reaction notes

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