229471-26-5Relevant articles and documents
A New and Efficient Synthesis of Pyrrolo[2,3-d]pyrimidine Anticancer Agents: Alimta (LY231514, MTA), Homo-Alimta, TNP-351, and Some Aryl 5-Substituted Pyrrolo[2,3-d]pyrimidines
Taylor, Edward C.,Liu, Bin
, p. 9938 - 9947 (2003)
Alimta, as well as homo-Alimta, a nonbridged analogue of Alimta, and TNP-351 have been prepared by a new method that involves Michael addition of the appropriate 1-nitroalkene with 2,6-diamino-3H-pyrimidin-4-one or 2,4,6-triaminopyrimidine, followed by a Nef reaction of the resulting primary nitro Michael adduct. Spontaneous intramolecular cyclization of the resulting aldehyde with the pyrimidine 6-amino group yields the corresponding pyrrolo[2,3-d]pyrimidine. A series of previously unknown 5-arylpyrrolo[2,3-d]pyrimidines was prepared by the same methodology from the above pyrimidines and nitrostyrenes. It has been found that the intermediate primary nitro Michael adduct can be prepared in a single step by sonication of a mixture of an arylaldehyde, nitromethane, and the 6-aminopyrimidine in acetic acid containing ammonium acetate.
Process for the preparation of pyrrolo[2,3-d]pyrimidines
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, (2008/06/13)
4(3H)-X-7H-Pyrrolo[2,3-d]pyrimidines in which X is =O or =NH are prepared by treating a 6-amino-4(3H)-X-pyrimidine with a unsubstituted or substituted 1-nitroalk-1-ene to yield a 6-amino-4(3H)-X-pyrimidine which is substituted in the 5-position by a 1-nitroalk-2-yl group; (ii) converting the 5-(1-nitroalk-2-yl)-6-amino-4(3H)-X-pyrimidine to the corresponding 5-(1-oxoalk-2-yl)-6-amino-4(3H)-X-pyr-imidine; and (iii) removing the elements of water from the 5-(1-oxoalk-2-yl)-6-amino-4(3H)-X-pyrimidine to effect cyclization. A typical embodiment involves treating 2,6-diamino-4(3H)-pyrimidone with 1-nitro-4-(4-ethoxycarbonylphenyl)-1-butene to yield 1 -nitro-2-(2,6-diamino-4(3H)-oxopyrimidin-5-yl)-4-(4-ethoxy-carbonylphenyl)butane which is then treated sequentially with base and acid, without isolation of the intermediate aldehyde, to form 4-[2-(2-amino-4(3H)-oxo-7H-pyrrolo[2,3-d]pyrimidin-5-yl)ethyl]benzoic acid, a valuable known chemical intermediate for the preparation of N-[4-{2-(2-hydroxy-4-amino-7H-pyrrolo[2,3-d]-pyrimidin-5-yl)ethyl}benzoyl]glutamic acid.
Exploitation of a new route to fused pyrroles: Synthesis of TNP-351, homo-MTA and 5-arylpyrrolo[2,3-d]pyrimidines
Taylor, Edward C.,Liu, Bin
, p. 4027 - 4030 (2007/10/03)
We have developed a new methodology for the construction of pyrrolo[2,3- d]pyrimidines that involves Michael addition of 2,6-diamino-4(3H)- pyrimidinone or 2,4,6-triaminopyrimidines to nitroolefins, followed by a Nef reaction of the resulting adduct to form an intermediate aldehyde that spontaneously cyclizes to the fused pyrrole ring. This methodology has been exploited in a new synthesis of TNP-351, and for the first reported preparation of homo-MTA and of a series of 5-arylpyrrolo[2,3-d]pyrimidines.
