Benzimidazole → HCID 178435477, compound

HRID 2360935Notes

Reaction equation

HRID 2360935 reaction equation
FC(F)(F)S([N:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]([N:17]3[CH2:22][CH2:21][CH2:20][C@@H:19]4[C:23]5[CH:24]=[C:25](OS(C(F)(F)F)(=O)=O)[CH:26]=[CH:27][C:28]=5[CH2:29][C@H:18]34)=[O:16])=[CH:14][C:9]=2[N:8]=[CH:7]1)(=O)=O.N1[C:44]2C=CC=C[C:43]=2NC=1>CN(C)C=O>[NH:6]1[C:10]2[CH:11]=[CH:12][C:13]([C:15]([N:17]3[CH2:22][CH2:21][CH2:20][C@@H:19]4[C:23]5[CH:24]=[C:25]([C:43]#[CH:44])[CH:26]=[CH:27][C:28]=5[CH2:29][C@H:18]34)=[O:16])=[CH:14][C:9]=2[N:8]=[CH:7]1

Participants

4

Reactant 2

HCID 5798BenzimidazoleHCID 86654157HCID 86654157, compound

Product 1

HCID 178435477HCID 178435477, compound

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

A flask charged with a stir bar, trifluoromethanesulfonic acid cis-1-(1-trifluoromethane-sulfonyl-1H-benzoimidazole-5-carbonyl)-2,3,4,4a,9,9a-hexahydro-1H-indeno[2,1-b]pyridin-6-yl ester (mixture of isomers regarding sulfonyl group attachment to N-1 or N-3 of the benzimidazole, 0.20 g) and N,N-dimethylformamide (2 mL) is sparged with argon for 5 min. Copper(I) iodide (13 mg), Pd(PPh3)2Cl2 (25 mg), triethylamine (0.31 mL), and trimethylsilylacetylene (0.14 mL) are added in the given order, the vessel is sealed, and the resulting mixture is heated to 60° C. After stirring the mixture at 60° C. overnight, it is cooled to room temperature and aqueous K2CO3 solution is added. The resulting mixture is extracted with ethyl acetate, the combined extract is dried (Na2SO4), and the solvent is evaporated. The residue is chromatographed on silica gel (dichloromethane/methanol 1:09:1) to afford the trimethylsilylated title compound which is taken up in methanol (3 mL) and treated with saturated aqueous K2CO3 solution at room temperature for 2 h. The mixture is then concentrated, water is added to the residue, and the resulting mixture is extracted with ethyl acetate. The combined extract is dried (Na2SO4) and concentrated. The residue is chromatographed on silica gel (dichloromethane/methanol 1:0→9:1) to afford the title compound. Yield: 0.03 g (26% of theory); LC (method 1): tR=2.65 min; Mass spectrum (ESI+): m/z=342 [M+H]+.

Workup

  1. additionA flask charged with a stir bar
  2. customis sparged with argon for 5 min
  3. additionCopper(I) iodide (13 mg), Pd(PPh3)2Cl2 (25 mg), triethylamine (0.31 mL), and trimethylsilylacetylene (0.14 mL) are added in the given order
  4. customthe vessel is sealed
  5. temperatureis cooled to room temperature
  6. additionaqueous K2CO3 solution is added
  7. extractionThe resulting mixture is extracted with ethyl acetate
  8. extractionthe combined extract
  9. dry with materialis dried (Na2SO4)
  10. customthe solvent is evaporated
  11. customThe residue is chromatographed on silica gel (dichloromethane/methanol 1:09:1)

Sources & evidence

ORD record
ord-6fe6376c33874a53bc35884facf910d0
Source dataset
uspto-grants-2014_04
Patent number
US08686149B2

Reaction notes

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