1-Bromo-3-chloropropane → HCID 68971707, compound

Temperature

70 °C

A mixture of 4-amino-2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-7-ol hydrochloride (prepared using a modification on the procedure described in Parts A and B of Example 51, 2.5 g, 7.4 mmol), 1-chloro-3-iodopropane (1.7 g, 8.2 mmol), and potassium carbonate (3.1 g, 22 mmol) in DMF (25 mL) was stirred overnight, then triethylamine (2 mL) was added and the reaction mixture was heated to 70° C. for 8 hours. The mixture was allowed to cool to room temperature and was stirred overnight. The mixture was poured into water (500 mL) and solid sodium hydroxide was added to adjust the mixture to pH 14. The mixture was extracted with chloroform (300 mL followed by 3×75 mL). The organic layers were thrown away and the aqueous layer was adjusted to pH 10 with 10% aqueous hydrochloric acid. A precipitate formed and was isolated by filtration. The solid was subjected to the initial reaction conditions, and this time methanol (25 mL) was added. After 3 hours at room temperature, the reaction mixture was heated at 90° C. and potassium carbonate (1 g) and 1-chloro-3-bromopropane (1 mL) were added. After 3 hours, the reaction mixture was allowed to cool to room temperature, was filtered, and the methanol was removed under reduced pressure. The solution was poured into water (300 mL) and sodium chloride (200 g) was added, causing a precipitate to form within 30 minutes. After 1 hour, the precipitate was filtered, dissolved in a minimal amount of chloroform, and purified by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 0-15% CMA in chloroform) to yield 900 mg of 7-(3-chloropropoxy)-2-(ethoxymethyl)-1-propyl-1H-imidazo[4,5-c]quinolin-4-amine.

1. customprepared
2. temperatureto cool to room temperature
3. stirringwas stirred overnight
4. additionwas added
5. extractionThe mixture was extracted with chloroform (300 mL followed by 3×75 mL)
6. customA precipitate formed
7. customwas isolated by filtration
8. customreaction conditions
9. waitAfter 3 hours at room temperature
10. temperaturethe reaction mixture was heated at 90° C.
11. waitAfter 3 hours
12. temperatureto cool to room temperature
13. filtrationwas filtered
14. customthe methanol was removed under reduced pressure
15. additionThe solution was poured into water (300 mL) and sodium chloride (200 g)
16. additionwas added
17. customto form within 30 minutes
18. waitAfter 1 hour
19. filtrationthe precipitate was filtered
20. dissolutiondissolved in a minimal amount of chloroform
21. custompurified by chromatography on a HORIZON HPFC system (silica gel, gradient elution with 0-15% CMA in chloroform)

ORD record

ord-4aa9d4cbc16e46eea83c8d72b5b7ded1

Source dataset

uspto-grants-2014_10

DOI

10.6084/m9.figshare.5104873.v1

Patent number

US08871782B2