Trifluoromethanesulfonic anhydride → 2-Benzyloxy-4-[5-(5-chloro-2-oxo-2H-[1,2']bipyridinyl-5'-ylmethyl)-imidazol-1-ylmethyl]-benzonitrile

HRID 1421744Notes

Reaction equation

HRID 1421744 reaction equation
[CH2:1]([O:8][C:9]1[CH:16]=[C:15]([CH2:17]O)[CH:14]=[CH:13][C:10]=1[C:11]#[N:12])[C:2]1[CH:7]=[CH:6][CH:5]=[CH:4][CH:3]=1.[Cl:19][C:20]1[CH:21]=[CH:22][C:23](=[O:57])[N:24]([C:26]2[CH:31]=[CH:30][C:29]([CH2:32][C:33]3[N:34]=[CH:35][N:36](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[CH:37]=3)=[CH:28][N:27]=2)[CH:25]=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>[CH2:1]([O:8][C:9]1[CH:16]=[C:15]([CH2:17][N:34]2[C:33]([CH2:32][C:29]3[CH:30]=[CH:31][C:26]([N:24]4[CH:25]=[C:20]([Cl:19])[CH:21]=[CH:22][C:23]4=[O:57])=[N:27][CH:28]=3)=[CH:37][N:36]=[CH:35]2)[CH:14]=[CH:13][C:10]=1[C:11]#[N:12])[C:2]1[CH:3]=[CH:4][CH:5]=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 212192292-Benzyloxy-4-hydroxymethyl-benzonitrileHCID 702869365-chloro-5'-(1-trityl-1H-imidazol-4-ylmethyl)-[1,2']bipyridinyl-2-one

Product 1

HCID 187797102-Benzyloxy-4-[5-(5-chloro-2-oxo-2H-[1,2']bipyridinyl-5'-ylmethyl)-imidazol-1-ylmethyl]-benzonitrile

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Conditions

Temperature
-78 °C

Procedure

To a cooled solution (-78° C.) of 2-benzyloxy-4-hydroxymethyl-benzonitrile from step 2 (100 mg, 0.42 mmol) and 5-chloro-5'-(1-trityl-1H-imidazol-4-ylmethyl)-[1,2']bipyridinyl-2-one from Example 23, Step 5 (221 mg, 0.42 mmol) in CH2Cl2 (2.1 ml) was added DIEA (325 μl, 0.92 mmol) followed immediately by the addition of Tf2O (160 μl, 0.63 mmol). The reaction mixture was 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 and heated to 60° C. for several hours. The MeOH was then removed in vacuo and the residue treated with saturated NaHCO3 (5 mL) and extracted with CH2Cl2 (2×10 mL). The organic layer was washed with brine, dried (MgSO4), filtered and concentrated. The residue was purified by flash chromatography [4% MeOH(5% NH4OH)/CH2Cl2 ] to yield the final 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
  5. temperatureheated to 60° C. for several hours
  6. customThe MeOH was then removed in vacuo
  7. additionthe residue treated with saturated NaHCO3 (5 mL)
  8. extractionextracted with CH2Cl2 (2×10 mL)
  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 [4% MeOH(5% NH4OH)/CH2Cl2 ]

Sources & evidence

ORD record
ord-6a692a27f7d349c7b5a3799b2a396f3d
Source dataset
uspto-grants-2000_06
Patent number
US06077853

Reaction notes

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