Trifluoroacetic acid → 1-(4-(3-(4-(5-Chloropyridin-2-ylamino)phenoxy)pyrazin-2-YL)piperidin-1-YL)ethanone

HRID 473706Notes

Reaction equation

HRID 473706 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]2[CH:34]=[CH:33][C:12]([O:13][C:14]3[C:15]([CH:20]4[CH2:25][CH2:24][N:23]([C:26]([O:28]C(C)(C)C)=O)[CH2:22][CH2:21]4)=[N:16][CH:17]=[CH:18][N:19]=3)=[CH:11][CH:10]=2)=[N:6][CH:7]=1.F[C:36](F)(F)C(O)=O.C(OC(=O)C)(=O)C>ClCCl>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]2[CH:34]=[CH:33][C:12]([O:13][C:14]3[C:15]([CH:20]4[CH2:25][CH2:24][N:23]([C:26](=[O:28])[CH3:36])[CH2:22][CH2:21]4)=[N:16][CH:17]=[CH:18][N:19]=3)=[CH:11][CH:10]=2)=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 6422Trifluoroacetic acidHCID 7918Acetic AnhydrideHCID 59374009Tert-butyl 4-(3-(4-(5-chloropyridin-2-ylamino)phenoxy)pyrazin-2-yl)piperidine-1-carboxylate

Product 1

HCID 593739651-(4-(3-(4-(5-Chloropyridin-2-ylamino)phenoxy)pyrazin-2-YL)piperidin-1-YL)ethanone

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent3×

Procedure

A solution of tert-butyl 4-(3-(4-(5-chloropyridin-2-ylamino)phenoxy)pyrazin-2-yl)piperidine-1-carboxylate (0.14 g, 0.29 mmol) in dichloromethane (1 mL) was added trifluoroacetic acid (0.22 mL, 2.9 mmol) and stirred at room temperature for 2 h. The reaction was concentrated in vacuo, and the residue was partitioned between CH2Cl2 and aqueous saturated NaHCO3 solution. The organic layer was dried (MgSO4), filtered, and concentrated in vacuo to give a golden yellow oil. A solution of the crude golden yellow oil in CH2Cl2 (1 mL) was cooled to 0° C. and added acetic anhydride (0.041 mL, 0.43 mmol). The reaction was gradually allowed to warm to room temperature and stirred for 1 h. The reaction was diluted with CH2Cl2 and washed with aqueous saturated NaHCO3 solution. The organic layer was dried (MgSO4), filtered, and concentrated in vacuo. Flash column chromatography (20% to 70% EtOAc/Hexanes) provided a crude crop of the desired product. Further purification via reverse phase HPLC afforded 1-(4-(3-(4-(5-chloropyridin-2-ylamino)phenoxy)pyrazin-2-yl)piperidin-1-yl)ethanone as an off-white amorphous solid. MS (ESI, pos. ion) m/z: 424.9 (M+1). IC50 (uM) 0.001.

Workup

  1. concentrationThe reaction was concentrated in vacuo
  2. customthe residue was partitioned between CH2Cl2 and aqueous saturated NaHCO3 solution
  3. dry with materialThe organic layer was dried (MgSO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto give a golden yellow oil
  7. temperatureto warm to room temperature
  8. stirringstirred for 1 h
  9. washwashed with aqueous saturated NaHCO3 solution
  10. dry with materialThe organic layer was dried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-eb9f1e6a0b8842aba07c96ad995132bd
Source dataset
uspto-grants-2014_01
Patent number
US08637500B2

Reaction notes

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