GB783306A - Trihalo-1-d-ribofuranosyl-benzimidazole compounds - Google Patents

Abstract

The invention comprises: (a) 4 : 5 : 6-(5 : 6 : 7)-trihalo - 1 - D - ribofuranosylbenzimidazoles of the general formula: <FORM:0783306/IV (a)/1> wherein each X represents a halogen atom and the halogen atoms may be the same or different (the position (4 or 7) of the third halogen atom has not been ascertained, and the numbering "4 : 5 : 6 - (5 : 6 : 7)" is used to indicate this and to identify the compounds with those obtainable by the process set out in (e) below); (b) triacyl derivatives of the compounds of (a); (c) acid addition salts of the compounds of (a) and (b); (d) phosphate esters (probably 51-phosphates but possibly including (b) triacyl derivatives of the compounds of (a); (c) acid addition salts of the compounds of (a) and (b); (c) acid addition salts of the compounds of (a) and (b); (d) phosphate esters (probably 5-phosphates but possibly including also 21- and 31-phosphates) of the compounds of (a), as obtainable by treating them with a phosphorylating agent (e.g. pyrophosphoric acid or phosphorus oxychloride pretreated with one molar equivalent of water); (e) the preparation of the compounds of (a) and (b) by the following series of steps, or by any part thereof including (iv) or (v) : (i) treating a 1 : 2 : 3 - trihalo - 4 : 5 - dinitrobenzene with a reducing agent to form a 1 : 2 : 3-trihalo-4 : 5-diaminobenzene; (ii) reacting the product of (i) with formic acid and a mineral acid to form a 4 : 5 : 6-trihalobenzimidazole; (iii) converting the product of (ii) to a 1-halomercuri derivative thereof by reaction with a mercuric halide (advantageously in the presence of NaOH, KOH, Ca(OH)2, Na2CO3 or KHCO3 and in solution in water or a lower alkanol); (iv) reacting the product of (iii) with a 1-halo-2 : 3 : 5-triacyl - D - ribofuranose to produce a compound (b); and (v) subjecting this to hydrolysis or alcoholysis (in alkaline or acid medium) to produce a compound (a). An example describes the complete process, starting with 1 : 2 : 3-trichloro-4 : 5-dinitrobenzene and using mossy tin and hydrochloric acid as the reducing agent in (i), hydrochloric acid as the mineral acid in (ii), mercuric chloride (in ethanol in the presence of dilute caustic soda) in (iii), 1-chloro-2 : 3 : 5-triacetyl - D - ribofuranose in dry xylene) in (iv), and methanol saturated with dry NH3 as alcoholysing agent in (v). The final product, 4 : 5 : 6 - (5 : 6 : 7) - trichloro - 1 - D - ribofuranosylbenzimidazole, is converted to its hydrochloride by saturating an ethanolic solution of the base with dry HCl. Lists are given of additional starting materials, intermediates and final products, including tribromo, dichloromonobromo, dibromo-monochloro, triiodo and dichloromonoiodo compounds, and acyl derivatives in which the acyl groups are propionyl, butyryl and benzoyl.