Trifluoromethanesulfonic anhydride → HCID 18690686, compound

HRID 2289643Notes

Reaction equation

HRID 2289643 reaction equation
[Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[CH:13]=[CH:12][C:11]([CH2:14][C:15]3[N:16]=[CH:17][N:18](C(C4C=CC=CC=4)(C4C=CC=CC=4)C4C=CC=CC=4)[CH:19]=3)=[CH:10][C:9]2=[O:39])[CH:5]=[CH:6][CH:7]=1.O[CH2:41][C:42]1[CH:49]=[CH:48][C:45]([C:46]#[N:47])=[C:44]([O:50][CH3:51])[CH:43]=1.C(N(CC)C(C)C)(C)C.FC(F)(F)S(OS(C(F)(F)F)(=O)=O)(=O)=O>C(Cl)Cl.CO>[Cl:1][C:2]1[CH:3]=[C:4]([N:8]2[CH:13]=[CH:12][C:11]([CH2:14][C:15]3[N:16]([CH2:41][C:42]4[CH:49]=[CH:48][C:45]([C:46]#[N:47])=[C:44]([O:50][CH3:51])[CH:43]=4)[CH:17]=[N:18][CH:19]=3)=[CH:10][C:9]2=[O:39])[CH:5]=[CH:6][CH:7]=1

Participants

7

Reactant 4

HCID 67749Trifluoromethanesulfonic anhydrideHCID 81531DiisopropylethylamineHCID 22016838HCID 22016838, compoundHCID 70276982HCID 70276982, compound

Product 1

HCID 18690686HCID 18690686, compound

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 6344DichloromethaneSolvent

Procedure

To a solution of 1-(3-Chloro-phenyl)-4-(1-trityl-1H-imidazol-4-ylmethyl)-1H-pyridin-2-one (272 mg, 0.527 mmol) from step 6 and 4-hydroxymethyl-2-methoxy-benzonitrile (90.3 mg, 0.55 mmol) in CH2Cl2 cooled to -78° C. over dry ice/acetone bath was added N,N-diisopropylethylamine (192 μl, 1.1 mmol) and trifluoromethane-sulfonic anhydride(93 μl, 0.55 mmol). The reaction was allowed to slowly warm to room temperature and stirred overnight. The reaction was diluted with methanol (10 mL), heated to reflux for 2 h, cooled and the solvent evaporated in vacuo. The residue was partitioned between sat. Na2CO3 (20 ml) and CH2Cl2 (2×50 ml). The organic extracts were dried (MgSO4) and evaporated in vacuo. The residue was chromatographed (silica gel, MeOH: CH2Cl2 3:97 to 4:96 to 10:90 gradient elution) to afford the free base which was converted to the hydrochloride salt to afford the title compound as an off white solid.

Workup

  1. temperatureheated
  2. temperatureto reflux for 2 h
  3. temperaturecooled
  4. customthe solvent evaporated in vacuo
  5. customThe residue was partitioned between sat. Na2CO3 (20 ml) and CH2Cl2 (2×50 ml)
  6. dry with materialThe organic extracts were dried (MgSO4)
  7. customevaporated in vacuo
  8. customThe residue was chromatographed
  9. wash(silica gel, MeOH: CH2Cl2 3:97 to 4:96 to 10:90 gradient elution)
  10. customto afford the free base which

Sources & evidence

ORD record
ord-6497f00ec72b48f3839046b7e44d95e1
Source dataset
uspto-grants-2000_07
Patent number
US06093737

Reaction notes

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