ChemInform Abstract: Dehydrogenation of 5,6‐Dihydropyrido[2,3‐d]pyrimidin‐7(8H)‐ones: A Convenient Last Step for a Synthesis of Pyrido[2,3‐d]pyrimidin‐7(8H)‐ones.

Abstract

Dehydrogenation of 5,6-Dihydropyrido[2,3-d]pyrimidin-7(8H)-ones: A Convenient Last Step for a Synthesis of Pyrido[2,3-d]pyrimidin-7(8H)-ones. -Two new protocols for the dehydrogenation of 5,6-dihydropyrido[2,3-d]pyrimidin--7(8H)-ones (I) are presented. -(PEREZ-PI, I.; BERZOSA, X.; GALVE, I.; TEIXIDO, J.; BORRELL*, J. I.; Heterocycles 82 (2010) 1, 581-591, http://dx.doi.org/10.3987/com-10-s(e)28 ; Grup Eng. Mol., Inst. Quim. Sarria, Univ. Ramon Llull, E-08017 Barcelona, Spain; Eng.) -H. Toeppel 19-153

Pyrido[2,3-d]pyrimidin-7(8H)-ones: Synthesis and Biomedical Applications

“…On the contrary, in the case of the structures 10 (C5-C6 double bond), 53.53% present only a substituent at C6 (R 5 = H) with the following distribution referring to the total number of structures: 44.46% carbon substituent [55,56] (32.12% phenyl ring [42,57,58]), 4.70% oxygen substituent [59,60], and 1.00% nitrogen substituent [32,61]. In 7.05% of the structures there is a substituent at C5 (R 6 = H) with the following distribution referring to the total number of structures: 4.16% carbon substituent [62,63] (0.10% phenyl ring [16,56]), 0.47% oxygen substituent [56,64], and 2.39% nitrogen substituent [64,65]. There is 7.75% of structures in which R 5 = R 6 = H [66,67].…”

“…In this synthetic approach, yields are higher than 60% in 840 cases of the 1476 reactions fully described (56.91%). A nice example of the first synthetic strategy is the synthesis of 19, an intermediate in the synthesis of palbociclib [90], starting from 5-bromo-2,4-dichloropyrimidine (15) which is substituted by cyclopentyl amine (16) to afford 17 which undergoes a palladium-catalyzed coupling with crotonic acid (18) followed by an intramolecular cyclization to yield the pyridopyrimidine system 19 ( Figure 10).…”

“…An example of the direct use of a pyrimidine ester is the formation of the 5-hydroxy substituted compound 26 starting from the ester 24 upon condensation with ethyl acetate (25) in a multistep protocol for which the yield is not described (Figure 12) [92]. A nice example of the first synthetic strategy is the synthesis of 19, an intermediate in the synthesis of palbociclib [90], starting from 5-bromo-2,4-dichloropyrimidine (15) which is substituted by cyclopentyl amine (16) to afford 17 which undergoes a palladium-catalyzed coupling with crotonic acid (18) followed by an intramolecular cyclization to yield the pyridopyrimidine system 19 ( Figure 10). Concerning the second synthetic strategy, an example of the use of a pyrimidine aldehyde for the construction of the pyridone ring is the synthesis of compound 23 [57], an intermediate for the synthesis of a series of tyrosine kinase inhibitors, starting from the aldehyde 20 which is condensed with the appropriate nitrile 21 to give the 7-iminopyridopyrimidine 22 that is subsequently transformed in the corresponding pyrido[2,3-d]pyrimidin-7(8H)-one (23) (Figure 11).…”

“…These compounds are subsequently converted to the desired 4-unsubstituted compound (55; R 4 = H) upon treatment with a guanidine carbonate 49 under microwave irradiation [99]. We completed our approach to totally dehydrogenated pyrido[2,3d]pyrimidin-7(8H)-ones (56)(57)(58) and (17; R 4 = H) by using several oxidation protocols [16]. The construction of the pyridopyrimidine structure from pyridone 47 usually proceeds with yields higher Only one example of the first kind of disconnection was found in SciFinder, the synthesis of compound 44 [94], an intermediate in the synthesis of pobosaibu, from pyridone 42 upon treatment with S-methylisothiourea (43) and DMF (N,N-Dimethylformamide) which provides the C4 carbon atom (yield not available) ( Figure 17).…”