Methanol carboxamidates

The aminolysis of esters of pyrimidine occurs normally to yield amides. The reagent is commonly alcoholic ammonia or alcoholic amine, usually at room temperature for 20-24 hours, but occasionally under refiux aqueous amine or even undiluted amine are used sometimes. The process is exemplified in the conversion of methyl pyrimidine-5-carboxylate (193 R = Me) or its 4-isomer by methanolic ammonia at 25 °C into the amide (196) or pyrimidine-4-carboxamide, respectively (60MI21300), and in the butylaminolysis of butyl ttracil-6-carboxylate (butyl orotate) by ethanolic butylamine to give A-butyluracil-5-carboxamide (187) (60JOC1950). Hydrazides are made similarly from esters with ethanolic hydrazine hydrate. 

Ethynyl-l-/3-D-ribofuranosylpyrazole-3-carboxamide was obtained in good yield by treatment of compound 48 with methanolic ammonia (96BMCL1279) (Scheme 97). 

This reaction to bicyclic compounds containing the aziridine group was also observed for other amides, viz., 44c-f, when treated with a catalytic amount of f-BuOK in THF or MeONa in methanol. LDA treatment of the tosyl-activated substrate 44 a gave the five-membered ring product albeit in a low yield (31 %). Remarkably, the carboxamide derived from the cz5-aziridine failed to react with base, probably due to steric hindrance. 

CASRN 148-79-8 molecular formula C10H7N3S FW 201.25 Photolytic. When thin films of thiabendazole on glass plates were exposed to sunlight for 128 d, benzimidazole-2-carboxamide and benzimidazole formed as photolysis products. Both compounds also formed when aqueous methanolic solutions of thiabendazole were subjected to UV light for 1 h (Zbozinek, 1984). 

Reduction of 3-aryl-4-oxo-4//-pyrido[2,l-fl]phthalazine-l-carboxamides with sodium cyanoborohydride in acidified methanol or lithium borohy-dride in tetrahydrofuran afforded 6,7-dihydro derivatives 47 (R = H) (88EUP294599). 

Diazoimidazole-5-carboxamide (9a) coupled in methanol with mer-capto derivatives to give the thioazo compounds 226 [73JAP24392 ... 

Ribavirin Ribavirin, l-j3-D-ribofuranosyl-l//-l,2,4-triazol-3-carboxamide (36.1.28), is synthesized by reacting methyl ester of l,2,4-triazol-3-carboxylic acid with 0-l,2,3, 5-tetraacetyl-j3-D-ribofuranose to make methyl ester of l-0-2,3,5-tetraacetyl-j3-D-ribofura-nosyl-l,2,4-triazol-3-carboxylic acid (36.1.27), which is treated with an ammonia solution of methanol to simultaneously dezacylate the carbohydrate part and amidation of the carboxyl part of the product to give ribavirin [29-37]. 

Alkaline hydrolysis of the carboxamide derivatives 142 upon heating in 1M KOH at reflux afforded the N-3-unsubstituted bicycle 143 (Equation 8) <1992FA1021>. Methanolic ammonia has also been used to remove the N-3-substituent from 144 giving 145 (Equation 9) <1996USP5508154>. 

Dicarboxanilide-acetylene Di(N-phenyl-carboxamide) acetylene or Bis(carboxanilide)- cetylene, CgHjHNOC.CsC.CONHCeHj mw 264.27, N 10.60% pinkish-white crysts (from MeOH-water), mp 194-96° was prepd from acetylenedicacboxylic acid by a series of reactions to give bromofumaranilide which was dehydrohalogenated by a dil soln of methanolic KOH. 

Treatment of ethyl l-oxo-l//-pyrimido[l,2-a]quinoline-2-carboxylates with ammonia in methanol and hydrazine hydrate in ethanol at ambient temperature afforded 2-carboxamides and 2-carbohydrazides, respectively (74MIP1 79MIP2). Reaction of l-oxo-l//-pyrimido[l,2,-a]quinoline-2-carboxylic acids (169) with A-. /V-carbonyldiimidazole in dimethyl-formamide, then with 5-aminotetrazole gave 7V-(5-tetrazolyl)-1 -oxo-1H-pyrimido[l,2-a]quinoline-2-carboxamides (170) (77GEP2630469 77USP 4017625). 

Ethyl 3-ethyl-2-methyl-4-oxo-4//-pyrido[ 1,2-a]pyrimidine-7-carboxyl-ate 486 reacted with ammonia, methylamine, and dimethylamine in methanol at ambient temperature for 3 days, with benzylamine at 175°C for 1 hour, and with hydrazine in boiling ethanol for 1 hour to afford the appropriate 7-carboxamides 487 and 7-carbohydrazide (83PHA218). The treatment of 7-carboxamide 487 (R = R1 = H) with boiling phosphoryl chloride for 1 hour afforded 7-nitrile 488. 7-Carboxylic acid chloride 490 was... 

A solution of 2-(N-methylbenzylidenehydrazo)-a-oxophenyl-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)carboxamide (37 mg) in methanol (1 ml) was treated with 2 N hydrochloric acid (0.1 ml) and left at room temperature for several hours. Evaporation of the solvent gave the crude product as a brown oil (36 mg). HPLC and MS analysis confirmed the structure and indicated a quantitative yield of endo-N-(9-methyl-9-azabicyclo[3.3.1]non-3-yl)-l-methylindazole-3-carboxamide (Ganisetron). 

A mixture of 34.4 g (100 mmol) 5-benzoyl-N-methyl-N-phenyl-2,3-dihydro-lH-pyrrolizine-l-carboxamide, 25 g sodium hydroxide in 25 mL water, and 80 mL methanol was refluxed for 5 hours. The mixture was cooled to room temperature, stirred under nitrogen for sixteen hours, and then diluted with 80 mL of water. The mixture was extracted with toluene, and the aqueous and organic phases were separated. The aqueous phase was acidified with 6 N hydrochloric acid. The resulting precipitate was extracted with dichloromethane. The combined extract was treated with activated clay decolorizing agent (4.5 g) for 30 minutes, filtered, and concentrated by... 

A mixture of 26.9 g (0.1 mol) of the 1,1-dioxide of methyl 4-hydroxy-2-methyl-2H-l,2-benzothiazine-3-carboxylate and 12.5 g (0.11 mol) of 2-amino-5-methylthiazole was refluxed in 4 liters of xylene for 24 hours in a nitrogen atmosphere. The methanol formed by the reaction was removed by means of a 4-A-molecular sieve mounted in a Soxhlet-extractor. The hot reaction solution was filtered. Upon cooling and standing overnight, the crude product separated out of the filtrate in the form of crystals (32.0 g, 91% of theory). After recrystallization from ethylene chloride 26.0 g (74% of theory) of 4-hydroxy-2-methyl-N-(5-methyl-2-thiazolyl)-2H-l,2-benzothiazine-3-carboxamide-1,1-dioxide were obtained M.P. 254°C (decomp.). 

A solution of 561 mg of 2-[3(S)-amino-2(R)-hydroxy-4-phenylbutyl]-N-tert-butyl-decahydro-(4aS,8aS) -isoquinoline-3(S)-carboxamide and 372 mg of N-(benzyloxycarbonyl)-L-asparagine in 20 ml of dry tetrahydrofuran was cooled in an ice/salt mixture. 189 mg of hydroxybenzotriazole, 161 mg of N-ethylmorpholine and 317 mg of dicyclohexylcarbodiimide were added and the mixture was stirred for 16 h. The mixture was then diluted with ethyl acetate and filtered. The filtrate was washed with aqueous sodium bicarbonate solution and sodium chloride solution. The solvent was removed by evaporation and the residue was chromatographed on silica gel using dichloromethane/methanol (9 1) for the elution to give 434 mg of 2-[3(S)-[[N-(benzyloxycarbonyl)-L-asparaginyl]amino]-2(R)-hydroxy-4-phenyl butyl]-N-tert-butyl-decahydro-(4aS,8aS)-isoquinoline-3(S)-carboxamide as a white solid from methanol/diethyl ether. 

About 10 g of VLB (vincaleucoblastine or simply vinblastine) sulfate were converted by standard procedures to VLB free base. The free base, obtained as a residue after evaporation of the dried ethereal solvent, was dissolved in about 200 ml of anhydrous methanol. Anhydrous liquid ammonia (300 ml) was added, and the reaction mixture sealed and maintained at about 100°C for 60 hours. The reaction vessel was opened, and the contents removed and evaporated to dryness in vacuo. The resulting residue, containing 4-desacetyI VLB C-3 carboxamide, as shown by thin layer chromatography, were combined and the solvent evaporated therefrom in vacuo, yielding asa residue purified 4-desacetyl VLB C-3 carboxamide free base. The NMR and IR spectra of the solid free base confirmed the structure indicated. The free base showed a band in the infrared at 1,687 cm-1, characteristic of the amide function. The molecular weight of the free base determined by mass spectroscopy was 753 which is in agreement with theoretical value calculated for C43H55N5O7. 

Irradiation of 3-chloro-A-phenylbenzo[Z ]thiophene-2-carboxamide and triethylamine in benzene/methanol (4/1) yielded [l]benzothieno[2,3-c]quinolin-6(5//)-one (92%)597. 

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