Trifluoroacetic acid → HCID 67044527, compound

HRID 2261958Notes

Reaction equation

HRID 2261958 reaction equation
[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([C:8]([C:10]2[CH:19]=[CH:18][CH:17]=[CH:16][C:11]=2[C:12]([O:14][CH3:15])=[O:13])=[O:9])=[CH:4][C:3]=1N(C(OC(C)(C)C)=O)C.FC(F)(F)[C:31]([OH:33])=[O:32].[C:36](=O)(O)[O-].[Na+].Cl.CN(C)CC[CH2:46][N:47]=[C:48]=[N:49]CC>ClCCl.CN(C)C=O>[CH3:46][N:47]1[C:3]2[CH:4]=[C:5]([C:8]([C:10]3[CH:19]=[CH:18][CH:17]=[CH:16][C:11]=3[C:12]([O:14][CH3:15])=[O:13])=[O:9])[CH:6]=[CH:7][C:2]=2[N:1]=[C:48]1[NH:49][C:31]([O:33][CH3:36])=[O:32]

Participants

7

Reactant 4

HCID 6422Trifluoroacetic acidHCID 516892Sodium BicarbonateHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 67044601HCID 67044601, compound

Product 1

HCID 67044527HCID 67044527, compoundYield 31%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 6344DichloromethaneSolvent

Conditions

Temperature
65 °C

Procedure

Methyl 2-({4-amino-3-[{[(1,1-dimethylethyl)oxy]carbonyl}(methyl)amino]phenyl}carbonyl)benzoate (0.167 g, 0.435 mmol) was dissolved in dichloromethane (1 mL) and treated with trifluoroacetic acid (0.7 mL) for 1.5 h. The mixture was brought to pH˜8 by addition of saturated sodium bicarbonate solution. The aqueous portion was partitioned with ethyl acetate. The organic portion was washed with brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford an orange foam which was dissolved in N,N-dimethylformamide (1 mL) and treated with methyl isothiocyanatidocarbamate (0.120 mL, 1.026 mmol). After 1 h, 1-(3-dimethylaminopropyl)-3-ethylcarbodiimide hydrochloride (0.120 g, 0.625 mmol) was added and the mixture was stirred at 65° C. for 0.5 h. The mixture was partitioned between ethyl acetate and lithium chloride (5% aqueous solution). The organic portion was washed with 0.5 N hydrochloric acid, saturated sodium bicarbonate solution, brine, dried over sodium sulfate, filtered and concentrated in vacuo to afford a yellow oil which was purified by column chromatography (ethyl acetate-hexanes 4:1) to afford methyl 2-[(1-methyl-2-{[(methyloxy)carbonyl]amino}-1H-benzimidazol-6-yl)carbonyl]benzoate as a colorless film (0.049 g, 0.134 mmol, 31% yield). 1H NMR (400 MHz, CDCl3): 11.4 (s, 1H), 8.06 (dd, 1H), 7.81 (d, 1H), 7.65 (td, 1H), 7.57 (td, 1H), 7.42 (dd, 1H), 7.39 (dd, 1H), 7.19 (d, 1H), 3.78 (s, 3H), 3.67 (s, 3H), 3.61 (s, 3H); MS (EI) for C19H17N3O5: 368 (MH+).

Workup

  1. customThe aqueous portion was partitioned with ethyl acetate
  2. washThe organic portion was washed with brine
  3. dry with materialdried over sodium sulfate
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customto afford an orange foam which
  7. additiontreated with methyl isothiocyanatidocarbamate (0.120 mL, 1.026 mmol)
  8. customThe mixture was partitioned between ethyl acetate and lithium chloride (5% aqueous solution)
  9. washThe organic portion was washed with 0.5 N hydrochloric acid, saturated sodium bicarbonate solution, brine
  10. dry with materialdried over sodium sulfate
  11. filtrationfiltered
  12. concentrationconcentrated in vacuo
  13. customto afford a yellow oil which
  14. customwas purified by column chromatography (ethyl acetate-hexanes 4:1)

Sources & evidence

ORD record
ord-c02c5c48a24c437ba229a6fac4b63689
Source dataset
uspto-grants-2010_12
Patent number
US07846959B2

Reaction notes

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