1,2-Dimethoxyethane → 2'-[(4-{[4-(Trifluoromethyl)phenyl]sulfonyl}-1-piperazinyl)carbonyl]-2,4'-bipyridine

HRID 41309Notes

Reaction equation

HRID 41309 reaction equation
Br[C:2]1[CH:7]=[CH:6][N:5]=[C:4]([C:8]([N:10]2[CH2:15][CH2:14][N:13]([S:16]([C:19]3[CH:24]=[CH:23][C:22]([C:25]([F:28])([F:27])[F:26])=[CH:21][CH:20]=3)(=[O:18])=[O:17])[CH2:12][CH2:11]2)=[O:9])[CH:3]=1.CC1(C)C(C)(C)OB([C:37]2[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=2)O1.C(=O)([O-])[O-].[Na+].[Na+].COCCOC>CCO.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1.O>[F:26][C:25]([F:28])([F:27])[C:22]1[CH:23]=[CH:24][C:19]([S:16]([N:13]2[CH2:14][CH2:15][N:10]([C:8]([C:4]3[CH:3]=[C:2]([C:37]4[CH:42]=[CH:41][CH:40]=[CH:39][N:38]=4)[CH:7]=[CH:6][N:5]=3)=[O:9])[CH2:11][CH2:12]2)(=[O:18])=[O:17])=[CH:20][CH:21]=1

Participants

8

Reactant 4

HCID 80711,2-DimethoxyethaneHCID 10340Sodium CarbonateHCID 11241171Pyridine-2-boronic acid, pinacol esterHCID 446121931-[(4-Bromo-2-pyridinyl)carbonyl]-4-{[4-(trifluoromethyl)phenyl]sulfonyl}piperazine

Product 1

HCID 446119622'-[(4-{[4-(Trifluoromethyl)phenyl]sulfonyl}-1-piperazinyl)carbonyl]-2,4'-bipyridineYield 1.3%

Reagents, catalysts & solvents 3

HCID 178418476HCID 178418476, compoundCatalystHCID 702EthanolSolvent2×HCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

In a 5 ml microwave vial were added 1-[(4-bromo-2-pyridinyl)carbonyl]-4-{[4-(trifluoromethyl)phenyl]sulfonyl}piperazine (Description 17) (150 mg, 0.314 mmol), 2-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)pyridine (Description 5) (129 mg, 0.627 mmol), bis(triphenylphosphine)palladium(II) chloride (44.0 mg, 0.063 mmol), sodium carbonate (100 mg, 0.941 mmol), 1,2-dimethoxyethane (1.5 ml), ethanol (1.0 ml) and water (0.50 ml). The reaction mixture was heated for 20 minutes at 120° C. in the microwave. The crude material was diluted in EtOH and filtered through celite. The filtrate was concentrated in vacuo then diluted with MeOH and filtered through an SCX cartridge (1 g). All material came out with MeOH wash so product concentrated, diluted with MeOH and filtered through a 5 g SCX column (washed with MeOH, eluted with NH3 0.5M in MeOH). The eluted product was concentrated in vacuo then dissolved in MeCN/DMSO 1:1 and purified by MDAP. The desired fractions were combined and concentrated under vacuo to give the title compound (2 mg).

Workup

  1. filtrationfiltered through celite
  2. concentrationThe filtrate was concentrated in vacuo
  3. additionthen diluted with MeOH
  4. filtrationfiltered through an SCX cartridge (1 g)
  5. washwash so product
  6. concentrationconcentrated
  7. additiondiluted with MeOH
  8. filtrationfiltered through a 5 g SCX column (washed with MeOH, eluted with NH3 0.5M in MeOH)
  9. concentrationThe eluted product was concentrated in vacuo
  10. dissolutionthen dissolved in MeCN/DMSO 1:1
  11. custompurified by MDAP
  12. concentrationconcentrated under vacuo

Sources & evidence

ORD record
ord-abc26f4c9434480d9c5f725ece41d10e
Source dataset
uspto-grants-2013_09
Patent number
US08530478B2

Reaction notes

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