Pyridine-2-carboxylates, 5- 4-methoxy

Pyridine, 4-methoxy-3-styryl-photoelectron spectroscopy, 2, 137 Pyridine, 2-methyI-alkylation, 2, 176 amination, 2, 233, 236 carboxylation, 2, 53 chlorination, 2, 201, 331 Claisen condensation, 2, 51 methiodide... 

Electronic effects on nickel-catalyzed oligomeriza-tions/polymerizations have been delineated through the use of a series of substituted pyridine carboxylate complexes, 12. The electron-rich methoxy-... 

Methyl 2-pyridinecarboxylate irradiated 2 min. at 32° under Ng with 254 nm light in methanol containing some H2SO4 -> methyl 6-methoxy-2-pyridine-carboxylate. Y 95%. F. e. s. T. Sugiyama et al., Tetrah. Let. 1974, 4339. 

The addition of Grignard reagents to aldehydes, ketones, and esters is the basis for the synthesis of a wide variety of alcohols, and several examples are given in Scheme 7.3. Primary alcohols can be made from formaldehyde (Entry 1) or, with addition of two carbons, from ethylene oxide (Entry 2). Secondary alcohols are obtained from aldehydes (Entries 3 to 6) or formate esters (Entry 7). Tertiary alcohols can be made from esters (Entries 8 and 9) or ketones (Entry 10). Lactones give diols (Entry 11). Aldehydes can be prepared from trialkyl orthoformate esters (Entries 12 and 13). Ketones can be made from nitriles (Entries 14 and 15), pyridine-2-thiol esters (Entry 16), N-methoxy-A-methyl carboxamides (Entries 17 and 18), or anhydrides (Entry 19). Carboxylic acids are available by reaction with C02 (Entries 20 to 22). Amines can be prepared from imines (Entry 23). Two-step procedures that involve formation and dehydration of alcohols provide routes to certain alkenes (Entries 24 and 25). 

Heating diethyl (l-isoquinolylamino)methylenemalonates in diphenyl ether gave ethyl 4-oxo-4//-pyrimido[2,l-a]isoquinoline-3-carboxylates (97) (78USP4127720). Cyclization of diethyl[(4-amino-l-isoquinolyl)amino] methylenemalonate in a mixture of acetic anhydride and pyridine in methylene chloride at ambient temperature afforded ethyl 7-acetylamino-4-oxo-4//-pyrimido[2,l-a]isoquinoline-3-carboxylate [84JAP(K)84/172472]. The 7-nitro derivative was prepared similarly. Cyclization of diethyl [(7-methoxy-3-methyl-l-isoquinolyl)amino]methylenemalonate in polyphos-phoric acid at 130°C for 6 h gave 10-methoxy-6-methyl-4//-pyrimido[2,l-a]isoquinolin-4-one in 29% yield [94IJC(B)795]. 

The methoxy group in 7-methoxy,2 7-methoxy-6-methyl,41 and 7-methoxy-4-methylisatin41 has been cleaved to the corresponding hydroxy group with pyridine hydrochloride, while treatment with sodium hydroxide cleaves the 6-methoxy group of 5-chloro-6,7-dimethoxy-l-methylisatin.48 5-Acetamidoisatins have been hydrolyzed to 5-aminoisatins.30 Isatin carboxylic acids have been converted to amides and esters by means of standard procedures.52,53... 

Hydroxybenzo[6]thiophene has been isolated from coal tar.42 It may be prepared from 6-aminobenzo[fr]thiophene by standard procedures.241 6-Methoxybenzo[h]thiophene may be prepared by decarboxylation of the corresponding 2-carboxylic acid,341 and 6-ethoxybenzo[6]thiophene is obtained by reduction of 6-(ethoxy)-thioindoxyl (Section VI, 1,2). 6-Methoxy-5-methylbenzo[6]thiophene is obtained by cyclization of (3-methoxy-4-methylphenylthio)-acetaldehyde dimethyl acetal (Section IV,B).617 The product previously described542 as 6-hydroxy-3-phenylbenzo[6]thiophene has now been shown to be the 2-phenyl isomer.307 6-Methoxy-818 and 6-methoxy-5-methyl-benzo[6]thiophene617 are demethylated by pyridine hydrochloride. 

In the event, iodolactonization of the carboxylate salt derived from the ester 458 afforded 459, and subsequent warming of the iodo lactone 459 with aqueous alkali generated an intermediate epoxy acid salt, which suffered sequential nucleophilic opening of the epoxide moiety followed by relactonization on treatment with methanol and boron trifluoride to deliver the methoxy lactone 460. Saponification of the lactone function in 460 followed by esterification of the resulting carboxylate salt with p-bromophenacylbromide in DMF and subsequent mesylation with methanesulfonyl chloride in pyridine provided 461. The diazoketone 462 was prepared from 461 by careful saponification of the ester moiety using powdered potassium hydroxide in THF followed by reaction with thionyl chloride and then excess diazomethane. Completion of the D ring by cyclization of 462 to the keto lactam 463 occurred spontaneously on treatment of 462 with dry hydrogen chloride. 

Reaction of 2-S-S-bis(5-methoxybenzimidazole) 1 with 3,5-dimethyl-4-methoxy-2-pyridine methyl carboxylate 2 followed by reaction with ammonia to give the carboxylate thioether 3. Compound 3 was oxidized to give the carboxylate sulfoxide 4 which was decarboxylated to give omeprazole 5. 

Reaction of 3,5-dimethyl-4-methoxy-2-chloromethylamido pyridine 1 with 5-methoxy-2-mercaptoimidazole 2 in a base to yield the acetamide thioether 3. Compound 3 was oxidized to the acetamide sulfoxide 4. Compound 4 was hydrolyzed to yield the carboxylate sulfoxide 5 which was then decarboxylated to give omeprazole 6. 

To a stirred suspension of p-(p-methoxybenzyloxy)-phenylmalonic acid (125 mg) in methylene chloride (3 ml) are added triethylamine (55 I) and oxalyl chloride (26 I) at -15°C, and the suspension is stirred for 40 minutes at 0°C. The mixture is added to a solution of diphenylmethyl 7p-amino-7a-methoxy-3-(l-methyltetrazol-5-yl)thiomethyl-l-oxadethia-3-cephem-4-carboxylate (100 mg) in methylene chloride (3 ml) and pyridine (63 I), and the mixture is stirred for 30 minutes at 0°C. The reaction mixture is diluted with ethyl acetate, washed with aqueous 2N-hydrochloric acid and water, dried over sodium sulfate, and concentrated to give crude product (212 mg), which is chromatographed on silica gel (20 g) and eluted with a mixture of ethyl acetate and acetic acid (99 1) to give diphenylmethyl-7p-[a-p-(p-methoxybenzyloxy)phenyl-a-carboxyacetamido]-7a-methoxy-3-(l-methyltetrazol-5yl)thiomethyl-l-oxadethia-3-cephem-4-carboxylate as foam (71 mg). Yield 45%. 

To a solution of the S-(+)-4-acethoxy-9-[2-(5-ethyl-l,2,3,6-tetrahydro-pyridin-3yl)-l-(lH-indol-2-yl)-l-methoxycarbonyl-ethyl]-3a-ethyl-5-hydroxy-8-methoxy-6-methyl-3a,4,5,5a,6,ll,12,12b-octahydro-lH-6,12a-diaza-indeno[7,l-ca]fluorene-5-carboxylic acid methyl ester in dioxane and glacial acetic acid was added 37% aqueous formaldehyde and the mixture stirred at 35°C for 24 h. The solution was evaporated in vacuo and the residue suspended in chloroform and washed with cold aqueous 5% K2C03 solution. The chloroform layer was dried (MgS04), filtered, and evaporated. The residue was chromatographed eluting with EtOAc/MeOH, 10% NH4OH to give the product navelbine. 

PYRIDINECARBONITRrLE, l,2-DIHYDRO-4-METHOXY-1-METHYL-2-OXO- see RJKIOO PYRIDINE-3-CARBOXYDIETHYLAMIDE see DJS200 PYRIDINE-3-CARBOXYLIC ACID see NCQ900... 

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