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

HRID 76882ノート

反応式

HRID 76882 の反応式
[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

参加物

6

反応物 4

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

生成物 1

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

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
60 °C

実験手順

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).

後処理

  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)

出典と根拠

ORDレコード
ord-7bf9c7ffd7944a5aa49bb72d99aa99a6
出典データセット
uspto-grants-2014_09
特許番号
US08835646B2

反応ノート

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