Alkylation indazole derivatives

A patent (95JAP07196655) deseribed the preparation of a 2//-indazole derivative of speeifie formula 109 useful as a therapeutie agent for a eireulatory disease sueh as hypertension, having angiotensin II antagonism and antihypertensive aetion. In formula 109 r = lower alkyl or alkenyl R, R = H, halogen, lower... 

Indazoles may be assembled via thermolysis as well. Treatment of diphenylcarbamoyl chloride with sodium azide gives rise to diphenyl-carbamoyl azide. Thermolysis of the diphenyl-carbamoyl azide then afforded indazolol. Subsequent alkylation of the indazolol then produced a series of indazole derivatives as activators of the nitric oxide receptor, soluble guanylate cyclise. 

Studies of the alkylation of indazoles (67HC(22)1) have been updated by Nunn (73JCS(PD2371) and Palmer (75JCS(P1)1695). The ratio of methylation at positions 1 and 2 is relatively sensitive to the steric effect of substituents at positions 3 and 7 as shown by the results obtained in basic medium for unsubstituted indazole (55 45) and its 3-phenyl (74 26) and7-nitro derivatives (29 71). 

NMR spectra of vicarious /V-alkylation products of 7-nitroinduzoles [672], l-benzylamino-3-nitroindazole [673], 1- and 6-nitroglucosylindazoles [674], l-acetyl-3-chloro-6-nitroindazole [675], the products of methylation and acetylation of 5- and 6-nitroindazoles in various solvents (CDC13, DMSO, acetone) [676], 5-nitro-7-methylindazole [677], 2-substituted 4,6-dinitroindazole [678], several dinitro indazoles [679], 6-nitroindazole derivatives [680], 44 nitrated 1- and 2-methylindazoles having H, Cl, and Br substituents in position 3 [681] have been obtained. II NMR data of some nitroindazoles are presented in a few studies [682-684],... 

Alkylation of 6-methylindazole with dihydropyran and acid produces the A-l-tetrahydropyranyl derivative as in N-l-acylation of indazoles, this 1-substituted product may be a thermodynamic product resulting from reversible alkylation. 

There have been relatively few previous reports of addition of acrylonitrile to heteroatomic systems. An examination of the reaction with indazoles revealed that alkylation rather than cycloaddition was the main course of reaction, but the diazole (213) did give two isomeric cyclobutane derivatives in poor yields. 2-Acyl-thio-... 

---