Sodium Iodide → 4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-nitrobenzonitrile

HRID 1877943Notes

Reaction equation

HRID 1877943 reaction equation
[C:1]([C:3]1[CH:21]=[CH:20][C:6]([CH2:7][N:8]2[C:12]([CH2:13][CH2:14]OS(C)(=O)=O)=[CH:11][N:10]=[CH:9]2)=[C:5]([N+:22]([O-:24])=[O:23])[CH:4]=1)#[N:2].[I-].[Na+].CCN(CC)CC.C(=O)([O-])[O-].[K+].[K+]>CN(C=O)C>[CH:11]1[N:10]=[CH:9][N:8]2[CH:7]([C:6]3[CH:20]=[CH:21][C:3]([C:1]#[N:2])=[CH:4][C:5]=3[N+:22]([O-:24])=[O:23])[CH2:14][CH2:13][C:12]=12

Participants

6

Reactant 4

HCID 5238Sodium IodideHCID 8471TriethylamineHCID 11430Potassium CarbonateHCID 86611070methanesulfonic acid 2-[3-(4-cyano-2-nitrobenzyl)-3H-imidazol-4-yl]ethyl ester

Product 1

HCID 588271134-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-nitrobenzonitrile

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
60 °C

Procedure

The crude residue, 4-[5-(2-hydroxyethyl)imidazol-1-ylmethyl]-3-nitrobenzonitrile, is then taken up in CH2Cl2 (10 mL), cooled to 0° C., and treated with Et3N (0.58 mL, 4.19 mmol). To this solution is added methanesulfonyl chloride (0.13 mL, 1.68 mmol). After 0.5 h the solution is diluted with CH2Cl2 (10 mL) and saturated aqueous NaHCO3 (20 mL). The organic layer is further extracted with CH2Cl2 (3×20 mL) and the combined layers are dried (Na2SO4) and concentrated to give crude methanesulfonic acid 2-[3-(4-cyano-2-nitrobenzyl)-3H-imidazol-4-yl]ethyl ester. A suspension of the methanesulfonic acid 2-[3-(4-cyano-2-nitrobenzyl)-3H-imidazol-4-yl]-ethyl ester residue, DMF (17 mL), sodium iodide (0.630 g, 4.19 mmol), Et3N (0.58 mL, 4.19 mmol), and potassium carbonate (0.580 g, 4.19 mmol) is heated to 60° C. for 1 hour and then 75° C. for an additional 2 h. At that point the suspension is concentrated and diluted with CH2Cl2 (20 mL) and saturated aqueous NaHCO3 (20 mL). The organic layer is further extracted with CH2Cl2 (3×20 mL) and the combined layers are dried (Na2SO4). The residue is then purified via HPLC (reversed phase, CH3CN/H2O) to give 4-(6,7-dihydro-5H-pyrrolo[1,2-c]imidazol-5-yl)-3-nitrobenzonitrile as a solid. MS (ESI) m/z 254.9 (M+H); 1H NMR (400 MHz, CDCl3) δ ppm 2.48-2.57 (m, 1 H), 2.81-2.92 (m, 1 H), 2.92-3.01 (m, 1 H), 3.35-3.47 (m, 1 H), 6.03 (dd, J=8.6, 3.5 Hz, 1 H), 6.80 (d, J=8.3 Hz, 1 H), 6.89 (s, 1 H), 7.36 (s, 1 H), 7.81 (dd, J=7.8, 1.8 Hz, 1 H), 8.41 (d, J=1.8 Hz, 1 H).

Workup

  1. concentrationAt that point the suspension is concentrated
  2. additiondiluted with CH2Cl2 (20 mL) and saturated aqueous NaHCO3 (20 mL)
  3. extractionThe organic layer is further extracted with CH2Cl2 (3×20 mL)
  4. dry with materialthe combined layers are dried (Na2SO4)
  5. customThe residue is then purified via HPLC (reversed phase, CH3CN/H2O)

Sources & evidence

ORD record
ord-f087c51666e044a69cdbfdf9a4d632c6
Source dataset
uspto-grants-2012_11
Patent number
US08314097B2

Reaction notes

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