223644-02-8Relevant articles and documents
Method for preparing isoquinoline hydrochloride intermediate and Rho kinase inhibitor by using BTC/Ph3PO chlorination system
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Paragraph 0128-0131, (2020/11/23)
The invention discloses a method for preparing an isoquinoline hydrochloride intermediate and an Rho kinase inhibitor by using a BTC/Ph3PO chlorination system, which comprises the following steps: putting an isoquinoline 5-sulfonic acid compound, BTC and a catalytic amount of Ph3PO into a reaction bottle, adding an organic solvent A, uniformly mixing all the components, and heating the mixture toreact; after the reaction is finished, carrying out suction filtration and drying to obtain a white solid isoquinoline hydrochloride intermediate, which is the isoquinoline 5-sulfonylchloride hydrochloride compound; concentrating a mother liquor part of the filtrate for separating out Ph3PO at a low temperature, and washing Ph3PO with a low-polarity solvent for recycling use. The method has the advantages of few side reactions, high product quality, less three-waste pollution, high atom economy and the like, the invention also provides a method for further preparing the Rho kinase inhibitor byutilizing the prepared isoquinoline hydrochloride intermediate; the impurities in the Rho kinase inhibitor prepared by the method are obviously lower than those in medicines obtained by a traditionalmethod.
A Practical synthesis of novel Rho-kinase inhibitor, (S)-4-fluoro-5-(2- methyl-1,4-diazepan-1-ylsulfonyl)-isoquinoline
Gomi, Noriaki,Ohgiya, Tadaaki,Shibuya, Kimiyuki,Katsuyama, Jyunji,Masumoto, Masayuki,Sakai, Hitoshi
experimental part, p. 1771 - 1781 (2011/09/21)
A practical synthesis of novel Rho-kinase inhibitor, (S)-4-fluoro-5- (2-methyl-1,4-diazepan-1-ylsulfonyl)isoquinoline hydrochloride dihydrate (1) was achieved in a pilot-scale production. We have demonstrated the regioselective chlorosulfonylation of 4-fluoroisoquinoline in an one-pot reaction to afford 4-fluoroisoquinoline-5-sulfonyl chloride and the asymmetric construction of the (S)-2-methyl-1,4-diazepane moiety as key steps. The Japan Institute of Heterocyclic Chemistry.