Trifluoroacetic acid → (1H-benzo[d]imidazol-2-yl)(4-(3-(piperidin-4-yl)pyrazin-2-yloxy)phenyl)methanone

HRID 555889Notes

Reaction equation

HRID 555889 reaction equation
[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([C:12]1[CH:37]=[CH:36][C:15]([O:16][C:17]2[C:18]([CH:23]3[CH2:28][CH2:27][N:26](C(OC(C)(C)C)=O)[CH2:25][CH2:24]3)=[N:19][CH:20]=[CH:21][N:22]=2)=[CH:14][CH:13]=1)=[O:11].FC(F)(F)C(O)=O>C(Cl)(Cl)Cl>[NH:1]1[C:5]2[CH:6]=[CH:7][CH:8]=[CH:9][C:4]=2[N:3]=[C:2]1[C:10]([C:12]1[CH:37]=[CH:36][C:15]([O:16][C:17]2[C:18]([CH:23]3[CH2:28][CH2:27][NH:26][CH2:25][CH2:24]3)=[N:19][CH:20]=[CH:21][N:22]=2)=[CH:14][CH:13]=1)=[O:11]

Participants

4

Reactant 2

HCID 6422Trifluoroacetic acidHCID 59351389tert-butyl 4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidine-1-carboxylate

Product 1

HCID 59351142(1H-benzo[d]imidazol-2-yl)(4-(3-(piperidin-4-yl)pyrazin-2-yloxy)phenyl)methanone

Reagents, catalysts & solvents 1

HCID 6212ChloroformSolvent

Procedure

To a flask containing tert-butyl 4-(3-(4-(1H-benzo[d]imidazole-2-carbonyl)phenoxy)pyrazin-2-yl)piperidine-1-carboxylate (230 mg, 0.460 mmol) is added chloroform (5 mL) and 2,2,2-trifluoroacetic acid (0.709 mL, 9.21 mmol). The reaction was stirred at rt 18 h. The solution was concentrated, followed by azeotropic removal of residual trifluoroacetic acid by concentration from toluene (5 mL×2). The crude salt was freebased by dissolving in MeOH and application to a 5 g Bondesil-SCX ion exchange column. Elution of the product with NH3 in MeOH (2.0 M) and concentration of the product containing fractions gives (1H-benzo[d]imidazol-2-yl)(4-(3-(piperidin-4-yl)pyrazin-2-yloxy)phenyl)methanone as a brown solid. MS (ESI, pos. ion) m/z: 400.0 (M+1). IC50 (uM) +++++.

Workup

  1. concentrationThe solution was concentrated
  2. customfollowed by azeotropic removal of residual trifluoroacetic acid by concentration from toluene (5 mL×2)
  3. dissolutionby dissolving in MeOH
  4. washElution of the product with NH3 in MeOH (2.0 M) and concentration of the product
  5. additioncontaining fractions

Sources & evidence

ORD record
ord-28e44526365247a683d74bff75bae634
Source dataset
uspto-grants-2011_11
Patent number
US08053438B2

Reaction notes

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