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

HRID 1877943노트

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HRID 1877943 반응식
[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

참가 물질

6

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

생성물 1

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

시약·촉매·용매 1

HCID 6228Dimethylformamide용매

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온도
60 °C

실험 절차

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).

후처리

  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)

출처 및 근거

ORD 기록
ord-f087c51666e044a69cdbfdf9a4d632c6
출처 데이터셋
uspto-grants-2012_11
특허 번호
US08314097B2

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