Trifluoroacetic acid → HCID 46199246, compound

HRID 1959348Notes

Reaction equation

HRID 1959348 reaction equation
C(OC([N:8](C(OC(C)(C)C)=O)[C:9]1[C:10]([C:16]2[N:20](C(OC(C)(C)C)=O)[C:19]3[CH:28]=[C:29]([CH3:32])[CH:30]=[CH:31][C:18]=3[N:17]=2)=[N:11][C:12](Br)=[CH:13][N:14]=1)=O)(C)(C)C.[NH:40]1[CH2:45][CH2:44]S[CH2:42][CH2:41]1.C1C=C(Cl)C=C(C(OO)=O)C=1.C(O)(C(F)(F)F)=O.C([O-])([O-])=O.[Na+].[Na+].[O-:70][S:71]([O-:74])(=S)=O.[Na+].[Na+]>CN(C=O)C.CCOC(C)=O>[O:70]=[S:71]1(=[O:74])[CH2:44][CH2:45][N:40]([C:12]2[N:11]=[C:10]([C:16]3[NH:20][C:19]4[CH:28]=[C:29]([CH3:32])[CH:30]=[CH:31][C:18]=4[N:17]=3)[C:9]([NH2:8])=[N:14][CH:13]=2)[CH2:41][CH2:42]1

Participants

8

Reactant 5

HCID 6422Trifluoroacetic acidHCID 67164ThiomorpholineHCID 70297m-Chloroperbenzoic acidHCID 20482104HCID 20482104, compoundHCID 86661948HCID 86661948, compound

Product 1

HCID 46199246HCID 46199246, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Conditions

Temperature
60 °C

Procedure

A solution of tert-butyl 2-[3-[bis(tert-butoxycarbonyl)amino]-6-bromo-pyrazin-2-yl]-6-methyl-benzimidazole-1-carboxylate (70 mg, 0.1158 mmol) in DMF (2 mL) was treated with thiomorpholine (59.74 mg, 0.5790 mmol) and heated to 60° C. for 3 hours. The mixture was then diluted with EtOAc, washed with water, brine, dried (MgSO4) and concentrated in vacuo. The residue was dissolved in DCM (10 mL), treated with mCPBA (59.95 mg, 0.3474 mmol) and stirred at RT for 1 hour. After washing with a 1:1 Na2CO3/Na2S2O3 solution, TFA (264.1 mg, 178.4 μL, 2.316 mmol) was added and the mixture stirred at RT for 1 hour. This was concentrated in vacuo and the resultant residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 uM, 100A column, gradient 10%-95% B (solvent A: 0.05% TFA in water, solvent B: CH3CN) over 16 minutes at 25 mL/min]. The fractions were collected and freeze-dried to give the title compound (13.1 mg, 31% Yield).

Workup

  1. washwashed with water, brine
  2. dry with materialdried (MgSO4)
  3. concentrationconcentrated in vacuo
  4. dissolutionThe residue was dissolved in DCM (10 mL)
  5. additionwas added
  6. stirringthe mixture stirred at RT for 1 hour
  7. concentrationThis was concentrated in vacuo
  8. customthe resultant residue was purified by reverse phase preparative HPLC [Waters Sunfire C18, 10 uM, 100A column, gradient 10%-95% B (solvent A: 0.05% TFA in water, solvent B: CH3CN) over 16 minutes at 25 mL/min]
  9. customThe fractions were collected
  10. customfreeze-dried

Sources & evidence

ORD record
ord-c62c62b36c5c479d86d1642890072497
Source dataset
uspto-grants-2013_04
Patent number
US08410112B2

Reaction notes

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