Pyridopyrimidines. 6. Nucleophilic substitutions in the pyrido[2,3-d]pyrimidine series

Synthesis of a Tetracyclic G∧C Scaffold for the Assembly of Rosette Nanotubes with 1.7 nm Inner Diameter

“…With this compound in hand, we explored the relative reactivity of positions C2, C4, and C7 toward S N Ar (Scheme ). On the basis of earlier work on simple chloro-substituted pyrido[2,3- d ]pyrimidines, , we anticipated that position C4 would be the most reactive. Thus, reaction with allylamine at −78 °C in CH 2 Cl 2 yielded compound 7 in 90% yield, whereas reaction with benzyl alcohol at −40 °C in CH 2 Cl 2 gave the desired compound 6 in 70% yield.…”

“…Given the challenges associated with the classical methods for the preparation of pyrido[2,3- d ]pyrimidines, − we chose to explore the formation of 2 using three regioselective S N Ar reactions at C2, C4, and C7 on the trichloro substituted molecule 1 . An earlier report by Broom and co-workers suggests that regioselective S N Ar on pyrido[2,3- d ]pyrimidine is a viable strategy, although to the best of our knowledge, C6-substituted pyrido[2,3- d ]pyrimidine have never been reported.…”

Pyridopyrimidines. 7. Ribonucleosides structurally related to the antitumor antibiotic sangivamycin

“…Evaporation of the ammonia gave a solid which was recrystallized from DMF to yield 2.35 g (77%) of 9. Dissolution in hot DMF, then addition of H20 to the cloud point and cooling afforded an analytical sample: mp 286-288 °C; UV (pH 1) 275 nm (e 40 000); (pH 7) 274 (43 400); (pH 11) 274 (43400); NMR 2.53 (s, 3 H. SCHA, 7.63.8.92 (br s, 2 H, NH2, JHnh ~4 Hz), 8.42,9.42 (br s. 2 H. CONH,, JHnh ~4 Hz), 3.37 (s, 3 H, CH;10), 5.70 6-Carboxamido-2,4-diamino-8-methoxymethyl-5-oxopyrido-[2,3-d]pyrimidine (10). To compound 8 (2.75 g, 7.33 mmol) in CHC13 (150 ml) at 5 °C was added m-chloroperbenzoic acid (3.75 g, 18.7 mmol) and the solution was stirred for 3 h. The solvent was removed in vacuo and the residue triturated with Et20 (50 ml), then filtered to give a white solid.…”

“…This mixture was obtained even when the oxidizing agent was used in excess. The mixture was treated with liquid ammonia to give a good yield of 6-carboxamido-2,4-diamino-8-methoxymethyl-5-oxopyrido[2,3-d]pyrimidine (10). The difference sulfoxide sulfone in reactivity of the esters of 6 and the oxidation products of 8 toward liquid ammonia may be explained by the electronwithdrawing effect of the methoxymethyl group which decreases electron density at the carbonyl carbon atom resulting in enhancement of reactivity, as compared to the electrondonating effect of the methyl group.…”

“…Synthesis and Stereochemistry of 3-Hydroxy-5-methylproline, a New Naturally Occurring Imino Acid Received September 3,1976 3-Hydroxy-5-methylproline was synthesized via Dieckmann cyclization of methyl N-methoxycarbonyl-3-methoxycarbonylmethylaminobutyrate (6) to A',2-dimethoxycarbonyl-5-methylpyrrolid-3-one (8). Reduction of the latter to lV,2-dimethoxycarbonyl-5-methylpyrrolidin-3-ol (9) and subsequent hydrolysis afforded a mixture (10) of the four diastereoisomers (1-4) of 3-hydroxy-5-methylproline, which were separated by ion-exchange chromatography. From NMR data and epimerization studies, the relative stereochemistry of these stereoisomers was established.…”