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

HRID 887477Notes

Reaction equation

HRID 887477 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-1f5a6f3a5e4f4d5d9bb375d2b847166a
Source dataset
uspto-grants-2012_08
Patent number
US08247418B2

Reaction notes

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