Hydrochloric Acid → 4-Amino-2-butyl-1-(2-hydroxy-2-methylpropyl)-7-methoxycarbonyl-1H-imidazo[4,5-c]quinoline

HRID 574006

반응식

HRID 574006 반응식
[NH2:1][C:2]1[CH:7]=[C:6]([C:8]([O:10][CH3:11])=[O:9])[CH:5]=[CH:4][C:3]=1[C:12]1[N:16]([CH2:17][C:18]([OH:21])([CH3:20])[CH3:19])[C:15]([CH2:22][CH2:23][CH2:24][CH3:25])=[N:14][C:13]=1[C:26]#[N:27].Cl.O1CCOCC1>>[NH2:27][C:26]1[C:13]2[N:14]=[C:15]([CH2:22][CH2:23][CH2:24][CH3:25])[N:16]([CH2:17][C:18]([OH:21])([CH3:19])[CH3:20])[C:12]=2[C:3]2[CH:4]=[CH:5][C:6]([C:8]([O:10][CH3:11])=[O:9])=[CH:7][C:2]=2[N:1]=1

참가 물질

4

반응물 3

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 867279605-(2-amino-4-methoxycarbonylphenyl)-2-butyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazole-4-carbonitrile

생성물 1

HCID 712840524-Amino-2-butyl-1-(2-hydroxy-2-methylpropyl)-7-methoxycarbonyl-1H-imidazo[4,5-c]quinoline수율 32%

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온도
25 °C

실험 절차

To 5-(2-amino-4-methoxycarbonylphenyl)-2-butyl-1-(2-hydroxy-2-methylpropyl)-1H-imidazole-4-carbonitrile S6 (118 mg, ˜90% pure, 0.27 mmol, 1.0 equiv) was added 4 N HCl in dioxane (2.0 mL, 8.0 mmol, 30 equiv) at 25° C. The reaction was heated at reflux for 15 h then cooled to 25° C. The reaction was concentrated in vacuo and partitioned between 1:9 MeOH/EtOAc (50 mL) and saturated NaHCO3 solution (10 mL). The aqueous layer was extracted with 1:9 MeOH/EtOAc (3×10 mL). The combined organic layers were washed with saturated aqueous NaCl, dried (MgSO4), and concentrated in vacuo. Purification by flash column chromatography on silica gel (CH2Cl2-1/9 MeOH/CH2Cl2, gradient) afforded the title compound 420 (95 mg, 32% over 2 steps) as an off white solid: 1H NMR (CD3OD, 600 Hz) δ1.02 (t, J=6.6 Hz, 3H), 1.28 (br s, 6H), 1.51 (hex, J=7.8 Hz, 2H), 1.88 (pent, J=7.2 Hz, 2H), 3.13 (t, J=7.2 Hz, 2H), 3.95 (s, 3H), 7.86 (dd, J=8.4, 1.8 Hz, 1H), 8.33 (d, J=1.8 Hz, 1H), 8.37 (d, J=8.4 Hz, 1H); 13C NMR (CD3OD, 150 Hz) δ 12.8, 22.2, 27.2, 29.7, 48.1, 51.3, 54.8, 71.1, 117.9, 118.6, 121.0, 121.3, 127.2, 127.9, 134.0, 143.6, 152.1, 157.3, 167.2; MS (APCI+): calcd C20H27N4O3 [M+H]+ 371.5. found 371.5.

후처리

  1. temperatureThe reaction was heated
  2. temperatureat reflux for 15 h
  3. concentrationThe reaction was concentrated in vacuo
  4. custompartitioned between 1:9 MeOH/EtOAc (50 mL) and saturated NaHCO3 solution (10 mL)
  5. extractionThe aqueous layer was extracted with 1:9 MeOH/EtOAc (3×10 mL)
  6. washThe combined organic layers were washed with saturated aqueous NaCl
  7. dry with materialdried (MgSO4)
  8. concentrationconcentrated in vacuo
  9. customPurification by flash column chromatography on silica gel (CH2Cl2-1/9 MeOH/CH2Cl2, gradient)

출처 및 근거

ORD 기록
ord-6558ea77374945d8b15aa8620e804515
출처 데이터셋
uspto-grants-2015_05
특허 번호
US09034336B2

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