Triethylamine → methanesulfonic acid 2-[3-(4-cyano-2-nitrobenzyl)-3H-imidazol-4-yl]ethyl ester

HRID 923262Notes

Reaction equation

HRID 923262 reaction equation
[OH:1][CH2:2][CH2:3][C:4]1[N:8]([CH2:9][C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][C:11]=2[N+:18]([O-:20])=[O:19])[CH:7]=[N:6][CH:5]=1.CCN(CC)CC.[CH3:28][S:29](Cl)(=[O:31])=[O:30]>C(Cl)Cl.C([O-])(O)=O.[Na+]>[C:14]([C:13]1[CH:16]=[CH:17][C:10]([CH2:9][N:8]2[C:4]([CH2:3][CH2:2][O:1][S:29]([CH3:28])(=[O:31])=[O:30])=[CH:5][N:6]=[CH:7]2)=[C:11]([N+:18]([O-:20])=[O:19])[CH:12]=1)#[N:15]

Participants

6

Reactant 3

HCID 8471TriethylamineHCID 31297Methanesulfonyl chlorideHCID 66886306HCID 66886306, compound

Product 1

HCID 86611070methanesulfonic acid 2-[3-(4-cyano-2-nitrobenzyl)-3H-imidazol-4-yl]ethyl ester

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolvent2×HCID 516892Sodium BicarbonateSolvent

Conditions

Temperature
0 °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, 1H), 2.81-2.92 (m, 1H), 2.92-3.01 (m, 1H), 3.35-3.47 (m, 1H), 6.03 (dd, J=8.6, 3.5 Hz, 1H), 6.80 (d, J=8.3 Hz, 1H), 6.89 (s, 1H), 7.36 (s, 1H), 7.81 (dd, J=7.8, 1.8 Hz, 1H), 8.41 (d, J=1.8 Hz, 1H).

Workup

  1. extractionThe organic layer is further extracted with CH2Cl2 (3×20 mL)
  2. dry with materialthe combined layers are dried (Na2SO4)
  3. concentrationconcentrated

Sources & evidence

ORD record
ord-1b143d71e9014a529ace8fe71cb8022e
Source dataset
uspto-grants-2016_03
Patent number
US09278969B2

Reaction notes

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