Trifluoroacetic acid → 1-(Methylsulfonyl)-4-[5-(pyridin-2-ylethynyl)pyridin-2-yl]piperazine

HRID 859915

Reaction equation

HRID 859915 reaction equation
[N:1]1[CH:6]=[CH:5][CH:4]=[CH:3][C:2]=1[C:7]#[C:8][C:9]1[CH:10]=[CH:11][C:12]([N:15]2[CH2:20][CH2:19][N:18](C(OC(C)(C)C)=O)[CH2:17][CH2:16]2)=[N:13][CH:14]=1.FC(F)(F)C(O)=O.C(N(CC)CC)C.[CH3:42][S:43](Cl)(=[O:45])=[O:44]>C(Cl)Cl>[CH3:42][S:43]([N:18]1[CH2:19][CH2:20][N:15]([C:12]2[CH:11]=[CH:10][C:9]([C:8]#[C:7][C:2]3[CH:3]=[CH:4][CH:5]=[CH:6][N:1]=3)=[CH:14][N:13]=2)[CH2:16][CH2:17]1)(=[O:45])=[O:44]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 69606771Tert-butyl 4-[5-(pyridin-2-ylethynyl)pyridin-2-yl)piperazine-1-carboxylate

Product 1

HCID 696067621-(Methylsulfonyl)-4-[5-(pyridin-2-ylethynyl)pyridin-2-yl]piperazineYield 98.1%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of tert-butyl 4-[5-(pyridin-2-ylethynyl)pyridin-2-yl]piperazine-1-carboxylate (3.8 g, 10.4 mmol) in CH2Cl2 (35 mL) at 0° C. was added trifluoroacetic acid (17.2 mL). The reaction was brought to room temperature and stirred for 30 minutes. Volatiles were removed in vacuo, and the residue was azeotroped with toluene (2×10 mL). The residue was then dissolved in CH2Cl2 and washed with aqueous sodium hydroxide solution (2M, 2×20 mL). The layers were then separated and the aqueous phase extracted with CH2Cl2 (3×10 mL). The combined organic extracts were then dried, (MgSO4), filtered and concentrated in vacuo. The residue was dissolved in CH2Cl2 (50 mL), and cooled to 0° C. and treated sequentially with triethylamine (1.5 mL, 16.7 mmol) and methanesulfonyl chloride (1.1 mL, 13.5 mmol). The reaction was brought to RT and stirred for 1 hour. The reaction was then quenched with water (50 mL). The layers were separated and the aqueous phase extracted with CH2Cl2 (3×20 mL). The combined organic extracts were then dried, (MgSO4), filtered and concentrated in vacuo. The residue was then purified by flash chromatography (silica gel, 10% MeOH in EtoAc) to give 1-(methylsulfonyl)-4-[5-(pyridin-2-ylethynyl)pyridin-2-yl]piperazine as a brown solid (3.5 g, 10.2 mmol, 98%).

Workup

  1. customwas brought to room temperature
  2. customVolatiles were removed in vacuo
  3. customthe residue was azeotroped with toluene (2×10 mL)
  4. dissolutionThe residue was then dissolved in CH2Cl2
  5. washwashed with aqueous sodium hydroxide solution (2M, 2×20 mL)
  6. customThe layers were then separated
  7. extractionthe aqueous phase extracted with CH2Cl2 (3×10 mL)
  8. dry with materialThe combined organic extracts were then dried, (MgSO4),
  9. filtrationfiltered
  10. concentrationconcentrated in vacuo
  11. dissolutionThe residue was dissolved in CH2Cl2 (50 mL)
  12. customwas brought to RT
  13. stirringstirred for 1 hour
  14. customThe reaction was then quenched with water (50 mL)
  15. customThe layers were separated
  16. extractionthe aqueous phase extracted with CH2Cl2 (3×20 mL)
  17. dry with materialThe combined organic extracts were then dried, (MgSO4),
  18. filtrationfiltered
  19. concentrationconcentrated in vacuo
  20. customThe residue was then purified by flash chromatography (silica gel, 10% MeOH in EtoAc)

Sources & evidence

ORD record
ord-5b7082bf53604a35baeab9708d9b557c
Source dataset
uspto-grants-2006_12
Patent number
US07153857B2

Linked notes

Loading…