Trifluoroacetic acid → 1-(Methylsulfonyl)-4-(5-{[5-(trifluoromethyl)pyridin-2-yl]ethynyl}pyridin-2-yl)piperazine

HRID 859920Notes

Reaction equation

HRID 859920 reaction equation
[F:1][C:2]([F:31])([F:30])[C:3]1[CH:4]=[CH:5][C:6]([C:9]#[C:10][C:11]2[CH:12]=[CH:13][C:14]([N:17]3[CH2:22][CH2:21][N:20](C(OC(C)(C)C)=O)[CH2:19][CH2:18]3)=[N:15][CH:16]=2)=[N:7][CH:8]=1.FC(F)(F)C(O)=O.C(N(CC)CC)C.[CH3:46][S:47](Cl)(=[O:49])=[O:48]>C(Cl)Cl>[CH3:46][S:47]([N:20]1[CH2:21][CH2:22][N:17]([C:14]2[CH:13]=[CH:12][C:11]([C:10]#[C:9][C:6]3[CH:5]=[CH:4][C:3]([C:2]([F:31])([F:30])[F:1])=[CH:8][N:7]=3)=[CH:16][N:15]=2)[CH2:18][CH2:19]1)(=[O:49])=[O:48]

Participants

6

Reactant 4

HCID 6422Trifluoroacetic acidHCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 69606756HCID 69606756, compound

Product 1

HCID 696067691-(Methylsulfonyl)-4-(5-{[5-(trifluoromethyl)pyridin-2-yl]ethynyl}pyridin-2-yl)piperazineYield 65%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
0 °C

Procedure

To a stirred solution of tert-butyl 4-(5-{[5-(trifluoromethyl)pyridin-2-yl]ethynyl}pyridin-2-yl)piperazine-1-carboxylate (724 mg, 1.67 mmol) in CH2Cl2 (8 mL) at 0° C. was added trifluoroacetic acid (4 mL). The reaction was brought to room temperature and stirred for 30 minutes. Volatiles were removed in vacuo. The residue was then dissolved in CH2Cl2 (20 mL) 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 (0.25 mL, 1.75 mmol) and methanesulfonyl chloride (0.14 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 to give 1-(methylsulfonyl)-4-(5-{[5-(trifluoromethyl)pyridin-2-yl]ethynyl}pyridin-2-yl)piperazine as an orange solid (445 mg, 1.08 mmol, 65%).

Workup

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

Sources & evidence

ORD record
ord-7df62743052a452b81c2700bb2500a2f
Source dataset
uspto-grants-2006_12
Patent number
US07153857B2

Reaction notes

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