Trifluoroacetic acid → (2'-Ethyl-5'-phenyl-1H,2'H-[3,3']bipyrazolyl-5-ylmethyl)-carbamic Acid Methyl Ester

HRID 585121Notes

Reaction equation

HRID 585121 reaction equation
[C:1]([O:5][C:6](=[O:27])[NH:7][CH2:8][C:9]1[NH:13][N:12]=[C:11]([C:14]2[N:15]([CH2:25][CH3:26])[N:16]=[C:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:18]=2)[CH:10]=1)(C)(C)C.FC(F)(F)C(O)=O.COC(N1C=CN=C1)=O>C(Cl)Cl.C(OCC)(=O)C.OS([O-])(=O)=O.[Na+]>[CH3:1][O:5][C:6](=[O:27])[NH:7][CH2:8][C:9]1[NH:13][N:12]=[C:11]([C:14]2[N:15]([CH2:25][CH3:26])[N:16]=[C:17]([C:19]3[CH:24]=[CH:23][CH:22]=[CH:21][CH:20]=3)[CH:18]=2)[CH:10]=1

Participants

7

Reactant 3

HCID 6422Trifluoroacetic acidHCID 580911Methyl 1H-imidazole-1-carboxylateHCID 10133577(2'-Ethyl-5'-phenyl-1H,2'H-[3,3']bipyrazolyl-5-ylmethyl)-carbamic Acid Tert-Butyl Ester

Product 1

HCID 9858466(2'-Ethyl-5'-phenyl-1H,2'H-[3,3']bipyrazolyl-5-ylmethyl)-carbamic Acid Methyl Ester

Reagents, catalysts & solvents 3

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolventHCID 516919Sodium BisulfateSolvent

Procedure

To a room temperature solution of the above-prepared (2′-ethyl-5′-phenyl-1H,2′H-[3,3′]bipyrazolyl-5-ylmethyl)-carbamic acid tert-butyl ester (25 mg, 68 μmoles) in CH2Cl2 (2 mL) was added trifluoroacetic acid (0.5 mL, excess). The resulting solution was stirred at room temperature for one hour, then concentrated and azeotroped with acetonitrile (3×) in vacuo. To the resulting crude deprotection product in acetonitrile was added triethylamine, then 1-methoxycarbonyl imidazole (26 mg, 204 μmoles) and the mixture was heated to 90° C. for two hours. The reaction was then cooled to room temperature, diluted with ethyl acetate and 1 M NaHSO4, and stirred vigorously for 20 minutes. The organic phase was washed with brine, dried over Na2SO4, filtered, and concentrated in vacuo. Flash chromatography (silica gel, hexanes/ethyl acetate gradient) provided the title compound as a white solid. 1H NMR (CDCl3, 400 MHz): 7.87 (d, 2H); 7.41 (dd, 2H); 7.37 (dd, 1H); 6.75 (s, 1H); 6.42 (s, 1H); 5.30 (dd, 1H); 4.68 (q, 2H); 4.40 (d, 2H); 3.73 (s, 3H); 1.51 (t, 3H).

Workup

  1. concentrationconcentrated
  2. customazeotroped with acetonitrile (3×) in vacuo
  3. additionTo the resulting crude deprotection product in acetonitrile was added triethylamine
  4. temperatureThe reaction was then cooled to room temperature
  5. stirringstirred vigorously for 20 minutes
  6. washThe organic phase was washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated in vacuo

Sources & evidence

ORD record
ord-42ca255e0aed40eda0754cf5e6037581
Source dataset
uspto-grants-2005_08
Patent number
US06930116B2

Reaction notes

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