2- Acyl-2,3-dihydro-17/-pyrido

Treatment of alkyl 9-benzyloxycarbonyl-3-methyl-6-oxo-2/7,6//-pyr-ido[2,l-f ][l,3]thiazine-4-carboxylates with BBr3 in CH2CI2 at -70 °C for 0.5-1 h and at room temperature for 3h yielded 9-carboxyl derivatives. The decarboxylation of these acids was unsuccessful. Hydrolysis of diethyl cA-3,4-H-3,4-dihydro-3-methyl-6-oxo-2//,6//-pyrido[2,l-f ][l,3]thiazine-4,9-dicarboxylate in aqueous EtOH with KOH at room temperature for 3 days yielded 4-ethoxycarbonyl-3,4-dihydro-3-methyl-6-oxo-2//,6//-pyrido-[2,l-f ] [1,3]thiazine-9-carboxylic acid (00JCS(P1)4373). Alkyl 9-hydroxy-methyl-3-methyl-6-oxo-3,4-dihydro-2//,6//-pyrido[2,l-f ][l,3]thiazine-4-car-boxylates were O-acylated with AC2O and (PhC0)20 in pyridine at room temperature for 12-48h. 

Piperazine NH group of 9-fluoro-10-(l-piperazinyl)-7-oxo-2,3-dihydro-7//-pyrido[l,2,3-<7e]-l,4-benzothiazine-6-carboxylate was reacted with 4-nitrophenylsulfonyl chloride, 2,6-dichloropyrazine, 2,6-dichloropyridine in DMF in the presence of pyridine, and with 4-nitrophenyl isothiocyanate in aqueous acetone in the presence of KOH (01MIP13). A side chain amino group on a 2,3-dihydro-7//-pyrido[l,2,3- fe]-l,4-benzothiazin-7-one skeleton was acylated (OOMIPIO). 

The hydroxy groups of 39 was acylated with acetic anhydride in pyridine (94JOC1358). The ester group of 4,5-difluoro-7-oxo-2,3-dihydro-7//-pyrido[3,2-l-(/ ][2,l]benzoxazine-8-carboxylate (40) was hydrolyzed under acidic conditions [92JAP(K)92/208288, 92JAP(K)92/210656],... 

The hydroxy group of 3-hydroxy-3,4-dihydro-2//-pyrido[l,2-a]pyrimi-dine was acylated with acid chlorides in pyridine341 and exchanged for chlorine by treatment with thionyl chloride.190 The resulting chloro derivative (131 mp = 46.5-47 C) was transformed on standing to a compound containing ionic chlorine (mp = 193 C). The structure of the latter remained unclarified.190... 

Reaction of potassium 9-fluoro-3-methyl-10-(4-methylpiperazin-l-yl)-2,3-dihydro-7H-pyrido[l,2,3-de][l,4]benzoxazine-6-carboxylate with 2-[3-(2,4-dichlorophenoxy)propyl]-3-[(2-chloroacetyl)amino]quinoxa-lin-4(3H)-one gave ester derivative of 2,3-dihydro-7H-pyrido[l,2,3-de] [l,4]benzoxazine-6-carboxylic acid. 3-Amino-2-(aryloxymethyl)quinox-alin-4(3H)-ones were N-acylated with 9-fluoro-3-methyl-10-(4-methyl-piperazin-l-yl)-2,3-dihydro-7H-pyrido[l,2,3-de][l,4]benzoxazine-6-car-boxylic acid chloride in the presence of K2C03 in boiling benzene for 6 h (07MI71). 

The piperazine moiety of 9-(l-piperazinyl)-7-oxo-2,3-dihydro-7//-pyrido[l,2,3-de]-l,4-benzothiazine-6-carboxylate was N-acylated with tri-fluoroacetic anhydride under reflux for 2 h (87JMC465). 

Acyl-2,3-dihydro-lH-pyrido[l, 2-c]pyrimidin-4-ones were obtained when 2-vinylpyridine was reacted with acyl isocyanates (75IZV2608), Cyclocondensation of 3-methoxy-2-(2-oxopropyl)piperidine and phenyl isothiocyanate in boiling ethylene dichloride afforded 3-methyl-5-meth-oxy-2-phenyl-2,4a,5,6,7,8-hexahydro-l//-pyrido[l,2-c]pyrimidine-l-thione (55JOC136). 

Acylation of 3-substituted indoles is more difficult, however 2-acetylation can be effected with the aid of boron trifluoride catalysis." " Indoles, with a carboxyl-containing side-chain acid at C-3, undergo intramolecular acylation forming cyclic 2-acylindoles." Intramolecular Vilsmeier processes, using tryptamine amides, have been used extensively for the synthesis of 3,4-dihydro-p-carbolines, a sub-structure found in many indole alkaloids (P-carboline is the widely used, trivial name for pyrido[3,4-fc]indole). Note that it is the imine, rather than a ketone, that is the final product the cyclic nature of the imine favours its retention rather than hydrolysis to amine plus ketone as in the standard Vilsmeier sequence " this ring closure is analogous to the Bischler-Napieralski synthesis of 3,4-dihydro-isoquinolines (9.15.1.7). 

Spirocyclic pyrido-l,3-oxazin-2-ones (277) can be obtained by the reactions of 2-amino-3-(l-hydroxycycloalkanyl)pyridines (276) with butyllithium and diethyl carbonate (Equation (26)) <89JHC113>, and l,4-dihydro-3,l-benzoxazin-2-ones (279) are available through the reactions of 2-benzoylphenyl isocyanates (278) with alcohols. The former are prepared by Friedel-Crafts acylation of benzene by 2-isocyanatobenzoyl chloride in the presence of aluminum(III) chloride (Scheme 81) and the whole process can be run as a one pot reaction <87JCR(S)96>. 

In contrast, aliphatic and aromatic carbonyl isocyanates react with 2-vinylpyridine to give 2-acyl-l-oxo-2,3-dihydro-l/f-pyrido[l,2c]pyrimidines 486... 

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