Claims for Patent: 5,925,760

Summary for Patent: 5,925,760

Title:	Method for preparing N2 -arylsulfonyl-L-argininamides
Abstract:	A method for preparing N2 -(3-(a hydrogen atom or a lower alkyl)-8-quinolinesulfonyl)-NG -nitro-L-arginine which comprises the step of condensing NG -nitro-L-arginine and 3-(a hydrogen atom or a lower alkyl)-8-quinolinesulfonyl chloride. The method achieves an extremely efficient and high yield preparation of N2 -arylsulfonyl-L-arginineamides that are useful as active ingredients of medicaments. Also provided is a novel N2 -(3-(a hydrogen atom or a lower alkyl)-8-quinolinesulfonyl)-NG -nitro-L-arginine compound which can be used as synthetic intermediate for the manufacture of (2R,4R)-4-methyl-1- N2 -(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl)-L-arginyl!-2-piperidine-carboxylic acid.
Inventor(s):	Ryoji Kikumoto
Assignee:	Mitsubishi Chemical Corp
Application Number:	US08/904,555
Patent Claims:	1. A method for preparing N2 -(3-(a hydrogen atom or a lower alkyl)-8-quinolinesulfonyl)-NG -nitro-L-arginine which comprises the step of condensing NG -nitro-L-arginine and 3-(a hydrogen atom or a lower alkyl)-8-quinolinesulfonyl chloride. 2. N2 -(3-(a hydrogen atom or a lower alkyl)-8-quinolinesulfonyl)-NG -nitro-L-arginine. 3. A method for preparing a lower alkyl ester of 1- NG -nitro-N2 -(3-(a hydrogen atom or a lower alkyl)-8-quinolinesulfonyl)-L-arginyl!-4-methyl-2-piperidine-carboxylic acid which comprises the step of condensing N2 -(3-(a hydrogen atom or a lower alkyl)-8-quinolinesulfonyl)-NG -nitro-L-arginine and a lower alkyl ester of 4-methylpiperidine-2-carboxylic acid. 4. The method according to claim 3, wherein the condensation is carried out in the presence of phosphorus oxychloride. 5. The method according to claim 3, wherein the ester compound is (2R,4R)-4-methylpiperidine-2-carboxylic acid ethyl ester. 6. The method according to claim 4, wherein the ester compound is (2R,4R)-4-methylpiperidine-2-carboxylic acid ethyl ester. 7. A method for preparing a lower alkyl ester of 1- NG -nitro-N2 -(3-(a hydrogen atom or a lower alkyl)-8-quinolinesulfonyl)-L-arginyl!-4-methyl-2-piperidine-carboxylic acid which comprises the steps of:(a) preparing N2 -(3-(a hydrogen atom or a lower alkyl)-8-quinolinesulfonyl-NG -nitro-L-arginine by reacting NG -nitro-L-arginine with 3-(a hydrogen atom or a lower alkyl)-8-quinolinesulfonyl chloride; and (b) condensing the N2 -(3-(a hydrogen atom or a lower alkyl)-8-quinolinesulfonyl)-NG -nitro-L-arginine obtained in the above step (a) with a lower alkyl ester of 4-methylpiperidine-2-carboxylic acid. 8. A method for preparing (2R,4R)-4-methyl-1- N2 -(3-methyl-1,2,3,4-tetrahydro-8-quinolinesulfonyl)-L-arginyl!-2-piperidine-carboxylic acid which comprises the step of hydrolyzing the lower alkyl ester of 1- NG -nitro-N2 -(3-(a hydrogen atom or a lower alkyl)-8-quinolinesulfonyl)-L-arginyl!-4-methyl-2-piperidine-carboxylic acid obtained according to the method of claim 7, and then subjecting the resulting hydrolysate to catalytic hydrogenation. 9. The method according to claim 7, wherein 3-methyl-8-quinolinesulfonyl chloride is used as the 3-(a hydrogen atom or a lower alkyl)-8-quinolinesulfonyl chloride and ethyl (2R,4R)-4-methylpiperidine-2-carboxylate is used as the lower alkyl ester of 4-methylpiperidine-2-carboxylic acid. 10. The method according to claim 8, wherein 3-methyl-8-quinolinesulfonyl chloride is used as the 3-(a hydrogen atom or a lower alkyl)-8-quinolinesulfonyl chloride and ethyl (2R,4R)-4-methylpiperidine-2-carboxylate is used as the lower alkyl ester of 4-methylpiperidine-2-carboxylic acid.