Potassium methyl derivatives

Amino-A.-selenazoline and its 5-methyl derivative have previously been obtained by Baringer (61) starting from 2-bromoethylamine hydrobromide and l-amino-2-bromopropane hydrobromide, respectively, by reaction with potassium selenocyanate. 

Both the 4- (38) and 6-(31) nitrimines are reduced with sodium boro-hydride to the corresponding y5-nitramine derivatives, e.g., (41)], which are methylated with methyl iodide and potassium carbonate. The A -methyl derivative is reduced in modest yield to the 5a-fluoride (43) with lithium aluminum hydride. 

The sodium or potassium salt of 6-azauracil in aqueous ethanol, anhydrous ethanol, or ethylene glycol reacted with methyl iodide practically exclusively to give the 3-methyl derivative (63). In toluene the sodium, potassium, and mercuric salts produced no methylated derivatives whereas the silver salt also yielded the 3-methyl derivative, Similarly, the 3-methyl derivative was prepared from the mercuric salt of 6-azathymine, and its structure was established by hydrolysis to pyruvic acid 4-methylthiosemicarbazone. ... 

The analogous 6-methyl derivative (126) was prepared by the same authors from 6-methyl-3,6-dithioxo derivative (123) as the corresponding monothioxo derivative is not easily available. Even here the substitution with ammonia took place selectively in position 4 (124) and the remaining sulfur atom was replaced with oxygen by oxidation with alkaline potassium permanganate (125). A similar procedure is protected by a patent. ... 

In contrast with cytosine, its aza analog readily undergoes hydrolysis both in acid and in alkaline solution. At 100°C hydrolysis is 50% complete within 10 min in a solution of hydrochloric acid or potassium hydroxide. The 5-methyl derivative is hydrolyzed even more readily. ... 

The 6-methyl derivative (98, R = Me) was an important intermediate in the synthesis of analogs (e.g., 183) of folic acid. Korte has shown that 2-aminopyrido[3,2-guanidine carbonate with 3-aminopicolinic acid and that treatment of the same acid with ammonium thiocyanate or potassium cyanate yields the thioureido and ureido derivatives (100, X = S and X = 0). In contrast to the pyrido[2,3-d]pyrimidine system bsoth of these compounds could be cyclized by heat and the latter (100, X = O) is a likely intermediate in the synthesis of the dione (98) by the fusion with urea. 

Treatment of a solution of the benzothiazepinedione 1 with ethanolic potassium hydroxide gives the potassium salt, which reacts with iodomethane (3 mol equiv) in a sealed tube at 100°C for three hours to give the (V-methyl derivative, 4-methyl-1,4-benzothiazepine-3,5(2//,4/7)-dione (2a).50 The (V-ethyl derivative 2b is prepared similarly.50... 

The potassium salt 2 of 5-amino-l,2,4,6-thiatriazepine-3,7(2//,4/f)-dithione is formed by the action of sulfur on dipotassium Ar-(cyanoformamidino)dithiocarbamate(l). The free thiol cannot be isolated, but its 5-methyl derivative 3 is obtained by treating the potassium salt 2 with iodomethane.380... 

Pyrazolotriazine 253 was prepared (88JOC887) by coupling 3-diazopyrazole 250 with isopropylidene malonate 251 via 252. Methylation of253 with methyl iodide in the presence of methanolic potassium hydroxide gave pyrazolotriazines 255 and 256, whereas mono N-methyl derivative 254 was prepared (88JOC887) by the action of dimethyl sulfate on 253 (Scheme 55). 

In the methylation reaction of 33 with methyl iodide in the presence of potassium carbonate, the A-methyl derivative 35 was formed, which epimerized to 34 on standing in CDCI3 solution at room temperature. This epimerization can be rationalized in terms of the favored N-inside conformation 33 with an equatorial aryl group. On A-methylation, the... 

The other way of synthesis of clozapine is from 8-chloro-10,ll-dihydro-5H-dibenzo[b,e]l, 4-diazepin-ll-thione, which is alkylated at the sulfur atom of the dibenzodiazepine ring by 4-nitrobenzylchloride in the presence of potassium fert-butoxide, giving iV-methyl derivative (6.5.8). Reaction of this with A-methylpiperazine gives the desired clozapine (6.5.7) [59]. 

A number of general methods for the synthesis of meso-ionic 1,2,4-triazol-3-ones are available. Sodium ethoxide-catalyzed cyclization of 1-benzoyl-l,4-diphenylsemicarbazide (201, R = R = R = Ph, X = O) yielded anhydro-3-hydroxy-1,4,5-triphenyl-1,2,4-triazolium hydroxide (200, R = R = R = Ph). A general route to meso-ionic 1,2,4-triazol-3-ones (200) is exemplified by the formation of the 1,4,5-triphenyl derivative (200, R = R = R = Ph) from A-amino-MA -diphenylbenzamidine (202, R = R = R = Ph) and phosgene. In contrast with this ready meso-ionic compound formation, the corresponding reaction of the iV-methylbenzamidine (202, R = Me, R = R = Ph) did not yield the meso-ionic 1,2,4-triazol-3-one (200, R = Me, R = R = Ph). The product was in fact 3,4-diphenyl-2-methyl-l,2,4-triazol-5-onium chloride (203), which on heating gave 3,4-diphenyl-1,2,4-triazol-5-one (204, R = Ph). The formation of the A-methyl derivative (200, R = Me, R = R = Ph, yield 79%) by heating the 7V-thiobenzoyl semicarbazide (201, R = Me, R = R = Ph, X = S) with potassium carbonate in methyl cyanide has been reported. Another synthesis of A-methyl derivatives (200, R = Me) involves methylation of 3-methyl-4-phenyl-l,2,4-triazol-5-one (204,... 

Reaction of the potassium salt of the [l,2,3]triazolo[4,5-d [l,2,5]oxadiazole 2-oxide 68 with AgNOs furnished the corresponding silver salt whilst the parent bicycle was obtained on acidification < 1996TL8577 >. Methylation of either the silver salt, or the parent bicycle, led to mixtures of the IV- and 0-methylated derivatives 67 and 69. In each case the selectivity of the reaction differed, the parent showed a 9 1 preference for the A-substituted derivative however, the 0-methylated product dominated and 67 and 69 resulted in a 4 3 ratio in the reaction starting from the silver salt (Scheme 5) <1996TL8577>. 

Other nucleophilic processes have included displacements of diazonium salts (66JMC733), and the reactions of potassium fluoride with 1-methoxy-2-phenyl-l,2,3-triazolium salts and their 4-methyl derivatives to give the... 

Treatment of 8-methyl derivatives (256) with potassium carbonate and alkyl halide results in C-alkylation of the 8-methyl group (i.e., 256-> 257) (Scheme 11). Reaction of the betaines (257) with hot aqueous potassium... 

For example, treatment of esters 819-21 with hydrazine in refluxing ethanol gave the N-unsubstituted bicycles 9 (R1 = H). 1-Methyl derivatives (9 R1 = Me) were also prepared.22 The hydrazine 11, obtained from the acid 10a, was heated at reflux without puriiication in dilute acid to give 12 (R = H). The acid chloride 10b furnished hydrazide intermediates 10c,17,23,24 which were cyclized by fusing the solid,23 refluxing with pyridine in the presence of copper powder,24 or by heating with potassium carbonate in 1-pentanol.17... 

The NH groups of sulfonamide functions are also readily alkylated. The 1,2,6-thiadiazine dioxide (74) gives the 2-methyl derivative on treatment with iodomethane in acetone in the presence of potassium carbonate <65CI(L)182). The 1,3,2,4,6-dithiatriazine (75) forms a silver salt (64MI22800), and reaction of the salt with iodomethane gives the expected TV-methyl compound. 

Schulte and Witt103 described the products obtained from the pyrido-[l,2-a]pyrimidine (63 R = H) with propargyl bromide and with 1-bromo-but-2-yne in methanolic potassium methoxide as the 2-alkoxy derivatives (mp = 200 C). Later, Katritzky and Waring273 proved these compounds to be the 1-alkyl derivatives. From 63 (R = H) with methyl iodide they obtained the 1-methyl derivative with propyl bromide, the 2-propyloxy derivative and with propargyl bromide, a mixture of the 1-propargyl and 2-pro-pargyloxy derivatives. 

Subsequently, a simpler procedure was devised for the preparation of (45) and the methyl derivative, chloro(acetylacetonato)-(ir-propen-2-ol)platinum(II) (48), which involved simply treating (43) with acetaldehyde or acetone in the presence of aqueous potassium hydroxide (45, 46). The respective a complexes are obtained as the potassium salts (46) and (47), most probably via attack by the a carbanion of the acetaldehyde or acetone on the platinum. 

The rates of hydrolysis and carbonyl-oxygen exchange carried out at 27°C with potassium hydroxide (1.5 N) on labeled N-benzyl-M-methyl derivatives of formamide (21 ), acetamide (22), and propionantide (23) have been reported (14). 

Similarly, the synthesis of 8,9-dihydropyrrolo[2,l-c/][l,5]benzothiazep-ine-7,10(6//,7u//)-dione 5,5-dioxides (16) was carried out by cyclizing l-(2-benzylsulfonylphenyl)pyrrolidin-5-one-2-carboxylates (15) in boiling xylene in the presence of potassium (Scheme 7) (72FES1003 73FES494). 7u-Carboxyethyl-8-methyl derivative 16 showed slight sedative activity (73FES494). 

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