5- Amino-l-methylimidazole-4-carboxamide

Intermediate ureido derivatives may be isolated in many of these reactions by working at lower temperatures as with l-methyl-4-methylaminoimidazole-5-iV-methylcarboxamide (341) which with urea at 140 °C in the presence of hydrogen chloride gave the ureidoimidazole (342). This then cyclized to theobromine with hot dilute acid (Scheme 136) (28CB1409). Potassium cyanate can sometimes replace urea, and with this reagent (341) was readily converted into caffeine (Scheme 136) (28CB1409), but on the other hand 5-amino-2-methylthio-l-methylimidazole-4-carboxamide failed to react. 

The first purine prepared from an imidazole was a 2-oxopurine, namely 7-methylxanthine (338), which was obtained from 4-amino-l-methylimidazole-5-carboxamide and diethyl carbonate in a sealed tube (Scheme 133) (24HCA713). 

Purine 9-oxides on the other hand are best made from imidazole precursors. Thus 9-hydroxy-8-methylxanthine (368) and hypoxanthine (369) have been most conveniently obtained by cyclization of 5-amino-l-benzyloxy-2-methylimidazole-4-carboxamide (370) with carbonate or formate esters, respectively, and debenzylation of the intermediate benzyloxy derivatives with hydrogen bromide in acetic acid (Scheme 156) (72JOC1867). 

A powdered mixture of 4-amino-l-methylimidazole-5-carboxamide hydrochloride (8g, 0.06 mol) and thiourea (12g, O.lSmol) was fused at 150 C for 25min. The cooled residue was dissolved in dil KOH and the solution boiled with a little charcoal and filtered. The filtrate, on acidification with HOAc, gave a light-brown solid yield , 3g (31%) mp > 360°C. 

Thus, 4-amino- l-methylimidazole-5-carboxamide (see 18) gave a good yield of 9-methylpurin-6-one (see 19) when refluxed with these reagents for 2 hr,201 and 4-aminoimidazole-5-carboxamide required only 30 min at 70°C.202 In the more 7i-deficient pyrazine series, 2 hr of boiling with the... 

---