4-Chloro-1-isobutyl-1H-imidazo[4,5-c]quinoline

Preparation of 4-ChIoro-l-isobutyl-lH- imidazo-[4, 5-c]-quinoline (V)The compound from (100 gm, 0.3603 moles) and phosphorous oxychloride (157 gm) were then added to N, N-Dimethylformamide (600ml) at 20Take the compound from Example (ii) (100 gm, 0.36 mole) and phosphorous oxychloride (157 gm) in N, N-Dimethylformamide (600 ml) at 20 EXAMPLE 8 4-Chloro-1-(2-methylpropyl)-1H-imidazo[4, 5-c]quinoline A suspension of 2-chloro-N4 -(2-methylpropyl)-3, 4-quinolinediamine (35 g) and triethylorthoformate (52.3 g, 2.5 eq) was heated at 145 C. for 10 h, during which time ethanol was removed by distillation. The resulting mixture was cooled to room temperature and the solid was removed by filtration. The solid was dissolved in hydrochloric acid (100 mL, 4N). The resulting solution was added to a solution of sodium hydroxide. The precipitate was filtered and washed with water to afford the product 4-chloro-1-(2-methylpropyl)-1H-imidazo[4, 5-c]quinoline in 92% yield.This example demonstrates the preparation of imiquimod by reaction of compound II with ammonia in DMSO at 140-150 C. under a pressure of about 5 bar.A 250 glass reactor 'Miniclave' was charged with Preparing Imiquimod (I) by Reacting Compound (II) with Formamide in the Presence of Ammonia (Bubbling During the Whole Course of the Reaction); A mixture of This example illustrates an exemplary process for preparing imiquimod by reaction of compound II with 10 equivalents of urea in DMSO at 135-140 C.A mixture of EXAMPLE 10 1-(2-Methylpropyl)-1H-imidazo[4, 5-c]quinolin-4-amine A mixture of Synthesis of Imiquimod A round-bottom three-necked flask equipped with condenser, magnetic stirrer, thermometer, is loaded with Preparation of Imiguimod (I) by Reacting Compound (II) with Formamide; A mixture of Examples 2-4; The data obtained by reacting the compound of formula (II) with formamide at different reaction temperatures for different reaction times is summarized in Table 1.EXAMPLE 6 1-(2-Methylpropyl)-1H-imidazo[4, 5-c]quinolin-4-amine A solution of EXAMPLE 77 Preparation of a Compound of Formula VII A mixture of 9.95 g (0.0412 mole) of 1-isobutyl-1H-imidazo [4, 5-c]quinolin-5-oxide (from Example 54) and 100 ml of phosphorus oxychloride was heated at its reflux temperature for 2.5 hours, and was then cooled and poured into ice with stirring. Basification (to pH 9-10) with 50% aqueous sodium hydroxide solution was followed by extraction with dichloromethane. The extracts were dried over sodium chloride and sodium bicarbonate, and were then evaporated to provide a solid residue. A sample of the residue was recrystallized from diethyl ether to provide EXAMPLE 96 Preparation of a Compound of Formula IX A mixture of 9.95 g (0.0412 mole) of 1-isobutyl-1H-imidazo[4, 5-c]quinolin-5-oxide (from Example 74) and 100 ml of phosphorus oxychloride was heated at its reflux temperature for 2.5 hours, and was then cooled and poured into ice with stirring. Basification (to pH 9-10) with 50% aqueous sodium hydroxide solution was followed by extraction with dichloromethane. The extracts were dried over sodium chloride and sodium bicarbonate, and then evaporated to provide a solid residue. A sample of the residue was recrystallized from diethyl ether to provide Step (D) To 40 ml of cold N, N-dimethylformamide (10-20 C.) was added slowly 5.9 g (0.0385 mole) of phosphorus oxychloride with swirling, the temperature of the mixture being maintained at 10-20 C. 1-Isobutyl-1H-imidazo[4, 5-c]quinolin-5-oxide (6.2 g; 0.0257 mole) from Step (C) above was added gradually with swirling and cooling. After addition was complete, the solution was allowed to stand at room temperature for about 30 minutes with occasional swirling. The solution was then heated on a steam bath for thirty minutes. After allowing it to cool, the solution was poured onto ice with stirring, and the resulting mixture was brought to pH 8-9 with concentrated ammonium hydroxide. The resulting off-white solid was filtered, washed with water, rinsed with ether, and dried to provide 6.0 g of crude Step (D) To 40 ml of cold N, N-dimethylformamide (10-20 C.) was added slowly 5.9 g (0.0385 mole) of phosphorus oxychloride with swirling, the temperature of the mixture being maintained at 10-20 C. 1-Isobutyl-1H-imidazo[4, 5-c]quinolin-5-oxide (6.2 g; 0.0257 mole) from Step (C) above was added gradually with swirling and cooling. After addition was complete, the solution was allowed to stand at room temperature for about 30 minutes with occasional swirling. The solution was then heated on a steam bath for thirty minutes. After allowing it to cool, the solution was poured onto ice with stirring, and the resulting mixture was brought to pH 8-9 with concentrated ammonium hydroxide. The resulting off-white solid was filtered, washed with water, rinsed with ether, and dried to provide 6.0 g of crude

Molecular Weight:259.73
XLogP3:3.9
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:2
Exact Mass:259.0876252
Monoisotopic Mass:259.0876252
Topological Polar Surface Area:30.7
Heavy Atom Count:18
Complexity:297
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes