Isoxazolo pyridine, synthesis from

SYNTHESIS FROM ACYCLIC PRECURSORS 7.08.11.1 Isoxazolo 4,3-c]pyridines... 

The electrophilic substitution in position 4 of the isoxazole ring is widespread for 3-AI and 5-AI however, the electrophilic substitution in position 3 or 5 of 4-AI has not been observed (Section III.A). Theoretically, one should expect the formation of isoxazolo[3,4-Z>]pyridines 20 and isoxazolo[5,4-Z>]pyridines 21 from 3-AI and 5-AI, correspondingly. A synthesis of isoxazolo[4,3-Z>]pyridines 22 or isoxazolo[4,5-Z>]pyridines 23 from 4-AI, with the substitution of hydrogen, seems impracticable (Scheme 11). 

Synthesis of isoxazolo[5,4- ]pyridines can be carried out from the corresponding chloronitrile intermediate 165 (Equation 64) <2002BML2925> or by deprotonation of an oxime with subsequent cyclization and expulsion of chloride (Equation 65) <1996JA10803>. Ring closure onto the nitrile in 166 by treatment with sodium hydroxide affords the isoxazolo[5,4- ]pyridine 167 in low yield (Equation 66) <1999JOC8479>. 

One synthesis of isoxazolo[5,4-Z>]pyrimidines from 4-unsubtituted 5-AI has been reported (Section III.C.2). As discussed above for isoxazolo[3,4-Z>]pyridines, the reaction of 3-amino-5-methylisoxazole with carbamate 44 does not produce isoxazolo [3,4-7>]pyrimidines, isoxazolo[2,3-a] 1.3.5-triazines 45 being formed as the only products. Meanwhile, the condensation of 5-amino-3-methylisoxazole with the same carbamate yielded isoxazolo[5,4-Z>]pyrimidine 46 (04KGS496) (Scheme 20). 

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