Dimethyl Sulfoxide → Imiquimod

HRID 549807Notes

Reaction equation

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]

Participants

Conditions

Temperature: 140 °C

Procedure

A mixture of 4-chloro-1-isobutyl-1H-imidazo[4,5-c]quinoline (II) (3 g, 0.0116 mol), urea (6.9 g, 0.116 mol, 10 equiv.) and DMSO (20 ml) was heated under stirring at 140° C. for 35 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 2.4 g of crude Imiquimod in 87.6% yield, having 99.0% purity (by HPLC, containing 1.0% of compound II).

Workup

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

Sources & evidence

ORD record: ord-1705b90dd5b942a5b499a65686aa7556
Source dataset: uspto-grants-2011_05
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07943771B2

Reaction notes

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