ChemicalBook CAS DataBase List Ripasudil Hydrochloride

Ripasudil Hydrochloride synthesis

7synthesis methods

Product Name:Ripasudil Hydrochloride
CAS Number:223644-02-8
Molecular formula:C15H19ClFN3O2S
Molecular Weight:359.8466

4-Fluoro-5-isoquinolinesulfonyl chloride hydrochloride (1:1)

906820-08-4
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194032-32-1
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223644-02-8
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Yield:223644-02-8 97%

Reaction Conditions:

with triethylamine in tetrahydrofuran at 0; for 2 h;

Steps:

42-43 Synthesis of Lisudil Hydrochloride

The 4-fluoroisoquinoline-5-sulfonyl chloride hydrochloride (37.12g, 131mmol) prepared in Example 33 in tetrahydrofuran (80ml) was dropped into the solution dissolved in tetrahydrofuran (100ml) at 0°C (S)-tert-butyl-3-methyl-1,4-diazepan-1-carboxylate (28.00g, 131mmol) and triethylamine (39.77g, 393mmol) system, stir two After hours, the solvent was evaporated, ethyl acetate (150ml) was added, and 1mol/L dilute hydrochloric acid was added to adjust the pH to 4.5. After thorough stirring, the layers were separated and the organic phase was discarded. The aqueous phase was extracted twice with dichloromethane (120mL ×2), then add 1mol/L dilute sodium hydroxide solution to the aqueous phase to adjust the pH to 11.5, add dichloromethane (150mL) for extraction, wash the organic phase with water, saturated brine, dry with anhydrous sodium sulfate, and evaporate under reduced pressure The solvent was removed to obtain (S)-(-)-1-(4-fluoroquinolin-5-yl)sulfonyl-2-methyl-1,4-diazepane as an oil. Add the obtained oil to methanol (150mL) and heat to dissolve it, adjust the pH to 5-6 with 12mol/L concentrated hydrochloric acid solution, stir and crystallize at room temperature, filter by suction and dry to obtain Lisudil Hydrochloride (45.72g, Yield 97%). The content by HPLC analysis was 99.99%, and the ee value was 99.99%. (The yield is calculated based on 4-fluoroisoquinoline-5-sulfonyl chloride hydrochloride).

References:

CN111909088,2020,A Location in patent:Paragraph 0128-0131