2- oxazolo pyridines

As reported in <1996GHEC-II(7)283>, no specific study on the mass spectra of these classes of compounds has been reported, although this analytical method has only been used as a tool for structure elucidation or reference without critical analysis. Some examples are reported in <1996GHEC-II(7)283>. Further information on the MS of heterocycles can be found in <2001MI1>. The mass spectral data for imidazopyridines, pyrazolo[3,4- ]pyridines, oxazolo-pyridines, ioxazolopyridines, isothiazolopyridines, 377-1,2-dithiolo[3,4- ]pyridines, and l,3-dithiolo[4,5- ]pyridines were reported in <1996GHEG-II(7)283>, but there have been no further reports in this area. 

This reaction procedure has also been used for the synthesis of oxazolo[3,2-fl]pyridine and imidazo[l,2-fl]pyridine derivatives, and the numerous variations studied, allowing changes of the substituent pattern and the number and position of the nitrogen atoms in the six-membered ring, are described in Chapters 4.10 and 4.29. 

Oxazolo[4,5-6]pyridin-2(3 H)-one IR, 6, 653 <76HCA1593) Oxazolo[4,5-fi]pyridin-2(3H)-one, 3-(4-chlorophenyl)-3a,7a-dihydro-6-methyl-X-ray, 6, 647 <79CPB2261) Oxazolo[4,5-6]pyridin-2(3H)-one, 3-(4-chlorophenyl)-3a,7a-dihydro-7a-methyl-X-ray, 6, 647 <79CPB2261) 5H-Oxazolo[3,2-a]pyridin-3(2H)-one, 2-phenyl-6,7,8,8a-tetrahydro-X-ray, 6, 646 <77MI42902) Oxazolo[5,4-d]pyrimidin-4-amine, A7-methyl- H NMR, 6, 650 <70BCJ3909)... 

Oxazolo[5,4-6]pyridine, 2-phenyl-applications, 6, 668 Oxazolo[3,2-a]pyri dines synthesis, 5, 121 6, 662 3ff-Oxazolo[3,4-a]pyridines partially saturated... 

Of the four possible oxazolopyridines, two have been studied with respect to quatemization reactions. Frazer and Tittensor prepared 2-alkyl- and 2-aryl-oxazolo[4,5-c]pyridines (105 Y = H) and converted them into methiodides, the structures of which have not been determined. Subsequently Takahashi et al. prepared the corresponding 5-methyl (105 Y = Me) and 2-methyl-5-nitro compounds and... 

Treatment of 3-phenylperhydro[l, 3]oxazolo[3,2-a]pyridine-5-carboxylates 303 and 304 with BF3 Et20 in THE, followed by reduction with NaBD4 afforded 6-deutero-4-phenylperhydropyrido[2,1 -c][l, 4]oxazin-1 -ones 220 and 222 (97JA6446). 

S,8aK)-8-acetoxytetrahydro-5- 2-propenyf)-3W-oxazolo[3,4-a]pyridin-3-one135 yield 88 %... 

One representative of the oxazolo[4,5-/][ 1,6]naphthyridine system, viz. the ester 62, is produced in four steps by annulation of 2-(dicthy lam ino)oxazolo[4,5- pyridine (Scheme 20). Whether the final product exists mainly as the hydroxy tautomer or as the 9//-6-one cannot be deduced from the spectral data presented alkylation occurs either at the oxygen or at N-9, and gives either 63 or 64 <1993SC2931>. 

Oxazolo[3,4-tf]pyridines 153, thiazolo[3,4- ]pyridines 155, and their fully saturated derivatives 154 and 156 were discussed in CHEC(1984) <1984CHEC(6)613> and CHEC-II(1996) <1996CHEC-II(8)249> very little information was available on the thiazolo[3,4- ]pyridine ring system while most of the information concerned the fully saturated oxygenated parent, oxazolo[3,4- ]pyridines. Careful examination of the literature clearly indicated that the situation has not changed much almost no references were reported on thiazolo[3,4-tf]pyridines and most of the work done in the last decade concerns the synthesis and reactivity of hexahydro-oxazolo[2,3-tf]pyridines 154. Therefore, this chapter will briefly describe the new reactions of fully conjugated systems and will focus on the partially/completely saturated derivatives (Scheme 45). 

An important feature of saturated oxazolo[3,4- ]pyridines is their easy epimerization at the aminal C-l stereocenter. A quite explicit example has been reported by Moloney et al. and is depicted in Scheme 46. The reaction between lactam 157 and benzaldehyde produces a mixture of hexahydro-oxazolo[3,4- ]pyridines, the kinetic product 158 being the major one. Equilibration of the mixture with boric acid allows the ratio of diasteroisomers to be reversed since /rarcr-oxazolidine 159 is now the major product <1998TL1025> the equilibration of epimeric oxazolidines via ring-chain tautomerism has been investigated in detail and explains the epimerization observed for some hexahydro-oxazolo[3,4-4]pyridines <1993JOC1967>. 

In contrast with the conjugated system, the reactivity of hexahydro-oxazolo[3,4- ]pyridines has been the subject of considerably more attention, which can most certainly be attributed to their greater synthetic potential, as demonstrated with the synthesis of many complex natural products. However, most of the reactions reported since 1996 have been known for many years, and the last decade was in fact characterized by their use in syntheses or optimization. After a brief survey of the thermal reactions, procedures involving the opening of the five-membered ring will be surveyed and the last part of this section will be devoted to the functionalization of the C-6 and C-7 positions. 

The ring rearrangement of 8a-(l-hydroxy-alkyl)-hexahydro-oxazolo[3,4- ]pyridin-3-ones 163 upon treatment with sulfuryl chloride was reported in 2004 activation of the alcohol and ring extension produces 5,6-dihydro-l//-oxazolo[3,4-tf]azepin-3-ones 164 in excellent yields (Scheme 48) <2004H(63)17>. 

Instead of water (or hydroxide ion), amines can be used to cleave the five-membered ring of tetrahydro-oxazolo[3,4- ]pyridine-l,3-dione 172 pipecolic acid amides 173 are usually obtained in good yields (36-93%, Scheme 50) <1998EJM23>. 

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