Glycine amide hydrochloride

The hydrolysis of glycine amide hydrochloride in sodium carbonate-sodium bicarbonate buffers is promoted by copper(II) and to a lesser extent by eobalt(II) and nickel(II) (148). The presence of 0.02 M copper(II) between pH 7.9 and 9.3 increases the rate of hydrolysis by a factor of about 30. This effect of metal ions on the rate of hydrolysis of glycine amide is surprisingly small when compared with the effect on the rate of hydrolysis... 

The same reagents can be used to form amides from carboxylic acids and amines, a method which is applicable to peptide synthesis. Condensation of A-benzyloxycarbonyl-L-phenylalanine and ethyl glycinate hydrochloride gave an 85% yield of purified dipeptide. 

Diazepam From a chemical point of view, diazepam, 7-chloro-l,3-dihydro-l-methyl-5-phenyl-2H-l,4-benzodiazepin-2-one (5.1.2), is the most simple of all of the examined derivatives of l,4-benzodiazepin-2-ones. Various ways for the synthesis of diazepam from 2-amino-5-chlorobenzophenone have been proposed. The first two ways consist of the direct cyclocondensation of 2-amino-5-chlorobenzophenone or 2-methylamino-5-chlorobenzophenone with the ethyl ester of glycine hydrochloride. The amide nitrogen atom of the obtained 7-chloro-l,3-dihydro-5-phenyl-2H-l,4-benzodiazepin-2-one (5.1.1), is methylated by dimethylsulfate, which leads to the formation of diazepam (5.1.2). 

The synthesis of (84) is effected by heating glycine in solvent such as ethylene glycol (Expt 8.38). Brief treatment with hot concentrated aqueous hydrochloric acid cleaves one of the amide linkages with the formation of the dipeptide, glycylglycine, which is isolated as the hydrochloride monohydrate and may be converted into the ester hydrochloride under Fischer-Speier conditions (Section 5.12.3, p. 696). 

Smooth esterification of 5-hydroxymethylpyrazol-3-one 71 was possible with A -Zcrt-butoxycarbonyl glycine 72 in 1,2-dichloromethane in the presence of DMAP and DCC to yield pyrazol-3-one ester 73 (02EJP121) (Scheme 18). Compound 71 was also esterified with 2-(6-methoxy-2-naphthyl)propionic acid 74 in DMF and in the presence of CDI to give pyrazol-3-one ester 75. Coupling of 5-aminomethylpyrazol-3-one hydrochloride 76 with trityloxyacetic acid 77 in DMF containing triethylamine and (benzotriazol-l-yloxy)trw(dimethylamino) phosphonium hexafluorophosphate (BOP) afforded pyrazol-3-one amide 78. 

Condensation of the hydroxy acid (241) with glycine /-butyl ester hydrochloride (242) smoothly proceeds in the presence of DEPC and NEt3 to give the amide (243).89 Amide 243 is used as an intermediate for the synthesis of topostin B567 (244) and topostin D654 (245) both have proved to be novel inhibitors of mammalian DNA topoisomerase.89... 

---