Sarcosine methyl ester

A variation on the usual synthesis of pyrazines, reaction of 1,2-diones with diamines, was the use of the diazabutadiene 81 in place of the dione <06JOC5897>. In another paper, the same diaza compound 81 reacted with sarcosine methyl ester, in a complex set of reactions, to produce quite good yields of 5-oxy-pyrazine-2-carboxamides 82. The A-methyl was lost and direct aromatisation occurred, presumably, due to cleavage oftheN-N bond <06SL2403>. 

The l-methylimidazole-5-aldehyde is easily accessible from sarcosine methyl ester hydrochloride and dimethylamino-2-azaprop-2-en-l-... 

Alkylation of pseudoephedrine sarcosinamide can be used to prepare enantiomerically enriched A -methyl-a-amino acids. Anhydrous pseudoephedrine sarcosinamide has been prepared by the addition of sarcosine methyl ester to a mixture of pseudoephedrine, lithium chloride, and lithium methoxide. In contrast to the preparation of pseudoephedrine glycinamide, the amount of dipeptide by-product produced in the reaction is minimal, perhaps due to the increased steric hindrance of the N-methyl group of sarcosine. Thus, pure anhydrous pseudoephedrine sarcosinamide can be obtained from the crude acylation reaction mixture by precipitation from toluene and subsequent drying. Like anhydrous pseudoephedrine glycinamide, anhydrous pseudoephedrine sarcosinamide can be handled in the atmosphere for brief periods without consequence, but should be stored with scrupulous avoidance of moisture to prevent hydration. 

Saligenin, 719 Sandmeyer reaction, 1098 Santonin, 19, 608 (—)-j8-Santonin, 995 Sarcosine methyl ester, 1160 Sarett reagent, 145-146 Schiff bases, 139, 273, 318, 428, 430, 746, 788, 885 reduction, 1230 Schiemann reaction, 394,1140 Scopoletin, 790 ScylUtol, 1209 Sebacamide, 1265 Sebadc acid, 584, 1265 Sebadl, 159... 

Polyamide resin, an alternative polymer support to polystyrene in SPPS. Polyamide resin is chemically more similar to the peptide chain itself The polyamide resin and the peptide chain would then be well solvated in dipolar aprotic solvents. A very successful member of polyamide resins consists of crosslinked polydimethylacry-lamide bearing sarcosine methyl ester side chains. These methyl ester moieties can then be modified by reaction with ethylene diamine. The resulting primary amino groups provide the points of attachment to the resin. In general, the properties of... 

Chloro-2-dibenzoylaminobenzyl bromide Sarcosine methyl ester Ethyl chloroformate... 

Dibenzyl phosphite was treated with sulphuryl chloride in toluene followed by cyanamide in aqueous alkali to give the salt (114). This was condensed with sarcosine methyl ester to give the imidazolinone (115) which after hydrogenolysis gave phosphocreatinine (116) Scheme 5.27.) [122],... 

The complex thioamide lolrestat (8) is an inhibitor of aldose reductase. This enzyme catalyzes the reduction of glucose to sorbitol. The enzyme is not very active, but in diabetic individuals where blood glucose levels can. spike to quite high levels in tissues where insulin is not required for glucose uptake (nerve, kidney, retina and lens) sorbitol is formed by the action of aldose reductase and contributes to diabetic complications very prominent among which are eye problems (diabetic retinopathy). Tolrestat is intended for oral administration to prevent this. One of its syntheses proceeds by conversion of 6-methoxy-5-(trifluoroniethyl)naphthalene-l-carboxyl-ic acid (6) to its acid chloride followed by carboxamide formation (7) with methyl N-methyl sarcosinate. Reaction of amide 7 with phosphorous pentasulfide produces the methyl ester thioamide which, on treatment with KOH, hydrolyzes to tolrestat (8) 2[. 

The interaction with both synthetic and naturally occurring amino acids has been studied extensively glycine (138, 173, 219-221), a-(173, 219) and /3-alanine (138, 220), sarcosine (219), serine (222), aspartic acid (138, 173, 222-226), asparagine (222), threonine (222), proline (219), hydroxyproline (219), glutamic acid (138, 222-225), glutamine (222), valine (219, 227), norvaline (219), methionine (222, 226), histidine (228, 229), isoleucine (219), leucine (219, 230), norleu-cine (219), lysine (222), arginine (222), histidine methyl ester (228), phenylalanine (138, 222), tyrosine (222), 2-amino-3-(3,4-dihydroxy-phenyl jpropanoic acid (DOPA) (222), tryptophan (222), aminoiso-butyric acid (219), 2-aminobutyric acid (219,231), citrulline (222), and ornithine (222). 

The synthesis of pyrrolo[2,3- 7 pyridazines can be achieved by starting either with pyridazine, a tetrazine, or a pyrrole. Pyridazinone 80 reacts with bromomethyl derivatives to give poor yields of 81 <1996H(43)1863> (Equation 34), while 5-acetyl-2-methyl-4-nitro-6-phenyl-3(2//)-pyridazinone, after treatment with sarcosine ethyl ester for a brief time at room temperature, followed by acid hydrolysis afforded a good yield of 82 (70%) <1994S669>. 

When cyanuric chloride reacts with DMF in t-butyl methyl ether it forms Gold s salt, [3-(dimethylamino)-2-azaprop-3-enylidene]dimethylammonium chloride, in almost quantitative yield. Methylate-promoted condensation of this salt with the methyl ester of sarcosine gives methyl 1-methylimidazole-5-carboxylate in up to 75% yield. The synthetic utility of this method is dependent on interception of the eliminated dimethylamine by addition of dimethyl oxalate and the bubbling of nitrogen through the solution [38]. 

The preparation of two of the three possible isomeric thieno-1,2-thiazin-4-ones (Schemes 5 and 6)128 involved reactions reported12 for the corresponding benzothiazines (see Scheme 1 ). Thus, methyl 3-chlorosul-fonylthiophene-2-carboxylate (152) with sarcosine ethyl ester gave thiophene sulfonamide (153) which, with methanolic sodium methoxide, yielded 3-methoxycarbonyl-4-hydroxy-2-methyl-2H-thieno[2,3-c]-l,2-thiazine 1,1-dioxide (154). Heating 154 with 2-aminothiazole gave 155, a thieno-1,2-thiazine analog of sudoxicam (20) (Scheme 5). 

Synthesis of Meso-ionic Thiazoles.—The anhydro-5-hydroxythiazolium hydroxide (43 R = SMe, R = COCF3) is obtained from the reaction between sarcosine, carbon disulphide, methyl iodide, and potassium hydroxide, followed by treatment of the intermediate MeSC(S)NMeCH2C02H (A) with trifluoroacetic anhydride. Methanolysis of (43) gives the methyl ester of the intermediate (A), whilst photolysis yields F3C0CH(C02Me)NMeCS2Me. 

Some amphoterics containing carboxylic acid functionality, such as the A-alkylami-nopropylglycines, can be analyzed readily by gas chromatography after formation of the methyl esters (97). Sodium lauroyl sarcosinate is readily determined after extraction from soap products with acidic DMF and subsequent derivatization with Ws(trimethylsilyl)-trifluoroacetamide/1% trichloromethylsilane (98). 

According to Eq. (11), Confalone has presented a new method of generation of azomethine ylides through the condensation of N-substituted ot-amino esters with aldehydes (83JOC2994 84JA7175). Thus, 5-formylmethyldibenzo-[a.d]tropylidene or o-(allyloxy)benzaldehyde is heated with ethyl sarcosinate or methyl prolinate under reflux in toluene. The water formed is continuously driven off with the aid of a Dean-Stark trap. The ester-stabilized azomethine ylide 77 or 78 quantitatively generated is trapped in an intramolecular fashion. 

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