Trifluoromethanesulfonic anhydride → (2-{5-[5-(5-chloro-2-oxo-2H-[1,2']bipyridinyl-5'-ylmethyl)-imidazol-1-ylmethyl]-2-cyano-phenoxy}-ethyl)-carbamic acid tert-butyl ester

HRID 1421733Notes

Reaction equation

HRID 1421733 reaction equation
[C:1]([O:5][C:6](=[O:21])[NH:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[C:15]([CH2:17]O)[CH:14]=[CH:13][C:12]=1[C:19]#[N:20])([CH3:4])([CH3:3])[CH3:2].[Cl:22][C:23]1[CH:24]=[CH:25][C:26](=[O:60])[N:27]([C:29]2[CH:34]=[CH:33][C:32]([CH2:35][C:36]3[N:37]=[CH:38][N:39](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[CH:40]=3)=[CH:31][N:30]=2)[CH:28]=1.CCN(C(C)C)C(C)C.O(S(C(F)(F)F)(=O)=O)S(C(F)(F)F)(=O)=O>C(Cl)Cl>[C:1]([O:5][C:6](=[O:21])[NH:7][CH2:8][CH2:9][O:10][C:11]1[CH:16]=[C:15]([CH2:17][N:37]2[C:36]([CH2:35][C:32]3[CH:33]=[CH:34][C:29]([N:27]4[CH:28]=[C:23]([Cl:22])[CH:24]=[CH:25][C:26]4=[O:60])=[N:30][CH:31]=3)=[CH:40][N:39]=[CH:38]2)[CH:14]=[CH:13][C:12]=1[C:19]#[N:20])([CH3:4])([CH3:3])[CH3:2]

Participants

6

Reactant 4

HCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 53993861[2-(2-Cyano-5-hydroxymethyl-phenoxy)-ethyl]-carbamic acid tert-butyl esterHCID 702869365-chloro-5'-(1-trityl-1H-imidazol-4-ylmethyl)-[1,2']bipyridinyl-2-one

Product 1

HCID 54572239(2-{5-[5-(5-chloro-2-oxo-2H-[1,2']bipyridinyl-5'-ylmethyl)-imidazol-1-ylmethyl]-2-cyano-phenoxy}-ethyl)-carbamic acid tert-butyl ester

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a cooled solution (-78° C.) of [2-(2-cyano-5-hydroxymethylphenoxy)-ethyl]-carbamic acid tert-butyl ester from step 3 (248 mg, 0.85 mmol) and 5-chloro-5'-(1-trityl-1H-imidazol-4-ylmethyl)-[1,2']bipyridinyl-2-one from Example 23, Step 5 (450 mg, 0.85 mmol) in CH2Cl2 (4.5 ml) was added DIEA (325 μl, 1.87 mmol) followed immediately by the addition of Tf2O (215 μl, 1.27 mmol). The reaction mixture stirred at -78° C. for 1 hour and was then transferred to an ice bath and stirred at 0° C. for another hour. The solvent was removed in vacuo. The residue was then dissolved in MeOH (4.5 ml) and heated to 60° C. for 4 hours. The MeOH was then removed in vacuo and the residue treated with saturated NaHCO3 and extracted with CH2Cl2. The organic layer was washed with brine, dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography with 0 to 4% MeOH(NH4OH 5%) in CH2Cl2 to yield the desired product.

Workup

  1. customwas then transferred to an ice bath
  2. stirringstirred at 0° C. for another hour
  3. customThe solvent was removed in vacuo
  4. dissolutionThe residue was then dissolved in MeOH (4.5 ml)
  5. temperatureheated to 60° C. for 4 hours
  6. customThe MeOH was then removed in vacuo
  7. additionthe residue treated with saturated NaHCO3
  8. extractionextracted with CH2Cl2
  9. washThe organic layer was washed with brine
  10. dry with materialdried (MgSO4)
  11. filtrationfiltered
  12. concentrationconcentrated
  13. customThe residue was purified by flash chromatography with 0 to 4% MeOH(NH4OH 5%) in CH2Cl2

Sources & evidence

ORD record
ord-af10b4c898b7492eabe9946bfece7d74
Source dataset
uspto-grants-2000_06
Patent number
US06077853

Reaction notes

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