Dimethyl Sulfoxide → Imiquimod

HRID 549808

反応式

HRID 549808 の反応式
Cl[C:2]1[C:11]2[N:12]=[CH:13][N:14]([CH2:15][CH:16]([CH3:18])[CH3:17])[C:10]=2[C:9]2[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=2[N:3]=1.[NH2:19]C(N)=O.CS(C)=O.[OH-].[Na+]>O>[CH3:17][CH:16]([CH2:15][N:14]1[C:10]2[C:9]3[CH:8]=[CH:7][CH:6]=[CH:5][C:4]=3[N:3]=[C:2]([NH2:19])[C:11]=2[N:12]=[CH:13]1)[CH3:18]

参加物

6

反応物 4

HCID 679Dimethyl SulfoxideHCID 1176UreaHCID 14798Sodium HydroxideHCID 3839614-chloro-1-isobutyl-1H-imidazo[4,5-c]quinoline

生成物 1

HCID 57469Imiquimod収率 88.5%

試薬・触媒・溶媒 1

HCID 962Water溶媒

反応条件

温度
157.5 °C

実験手順

A mixture of 4-chloro-1-isobutyl-1H-imidazo[4,5-c]quinoline (II) (3 g, 0.0116 mol), urea (13.8 g, 0.232 mol, 20 equiv.) and DMSO (25 ml) was heated under stirring at 155-160° C. for 12 hours. Then, the reaction mixture was cooled to 80° C. and water (30 ml) and 46% aqueous NaOH solution were added to produce a pH of 10-11. The mixture was stirred at ambient temperature for 1 hour and a precipitate was collected by filtration. The wet compound was treated with water (20 ml) at 70-80° C. under stirring for 1 hour. A solid was collected by filtration from the hot mixture, washed with water (3×20 ml) and methanol (20 ml) and dried at 80° C. under reduced pressure overnight to yield 2.45 g of crude imiquimod in 88.5% yield, having a purity of 99.0% (by HPLC, containing 1.0% of the compound II). The crude imiquimod was purified by the method presented in Example 1 to obtain 2.15 g of imiquimod in 87.8% yield; total yield: 77.7%; having a purity of 99-93% (by HPLC).

後処理

  1. temperaturewas heated
  2. temperatureThen, the reaction mixture was cooled to 80° C.
  3. customto produce a pH of 10-11
  4. stirringThe mixture was stirred at ambient temperature for 1 hour
  5. filtrationa precipitate was collected by filtration
  6. additionThe wet compound was treated with water (20 ml) at 70-80° C.
  7. stirringunder stirring for 1 hour
  8. filtrationA solid was collected by filtration from the hot mixture
  9. washwashed with water (3×20 ml) and methanol (20 ml)
  10. customdried at 80° C. under reduced pressure overnight

出典と根拠

ORDレコード
ord-636daeb3c90145d69e2e37eaa86aeceb
出典データセット
uspto-grants-2011_05
特許番号
US07943771B2

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