Skip to Content

Synthesis of 2-arylamino substituted 5,6-dihydropyrido[2,3-d]pyrimidine-7(8H)-ones from arylguanidines.

Synthesis of 2-arylamino substituted 5,6-dihydropyrido[2,3-d]pyrimidine-7(8H)-ones from arylguanidines.

Molecular diversity (2012-10-12)

Iñaki Galve, Raimon Puig de la Bellacasa, David Sánchez-García, Xavier Batllori, Jordi Teixidó, José I Borrell

ABSTRACT

A practical protocol was developed for the synthesis of 2-arylamino substituted 4-amino-5,6-dihydropyrido[2,3-d]pyrimidin-7(8H)-ones from α,β-unsaturated esters, malononitrile, and an aryl substituted guanidine via the corresponding 3-aryl-3,4,5,6- tetrahydropyrido[2,3-d]pyrimidin-7(8H)-ones. Such compounds are formed upon treatment of 2-methoxy-6-oxo-1,4,5,6-tetrahydropyridine-3-carbonitriles with an aryl substituted guanidine in 1,4-dioxane and are converted to the desired 4-aminopyridopyrimidines with NaOMe/MeOH through a Dimroth rearrangement. The overall yields of this three-step protocol are, generally speaking, higher than the multicomponent reaction, previously developed by our group, between an α,β-unsaturated ester, malononitrile, and an aryl substituted guanidine.

MATERIALS

Product Number

Brand

Product Description

Sigma-Aldrich

1,4-Dioxane solution, NMR reference standard, 40% in benzene-d₆ (99.6 atom % D), NMR tube size 10 mm × 8 in.

Sigma-Aldrich

1,4-Dioxane, suitable for HPLC

Sigma-Aldrich

1,4-Dioxane, SAJ first grade

Sigma-Aldrich

1,4-Dioxane solution, NMR reference standard, 10 mM in D₂O ("100%", 99.96 atom % D), NMR tube size 5 mm × 7 in.

Supelco

1,4-Dioxane solution, NMR reference standard, 40% in benzene-d₆ (99.6 atom % D), NMR tube size 5 mm × 8 in.

Sigma-Aldrich

1,4-Dioxane, anhydrous, 99.8%, contains <=25 ppm BHT as stabilizer

Supelco

1,4-Dioxane, analytical standard

Sigma-Aldrich

1,4-Dioxane solution, NMR reference standard, 40% in benzene-d₆ (99.6 atom % D), chromium(III) acetylacetonate 5 mg/mL, NMR tube size 5 mm × 8 in.

Sigma-Aldrich

1,4-Dioxane solution, NMR reference standard, 40% in benzene-d₆ (99.6 atom % D), chromium(III) acetylacetonate 5 mg/mL, NMR tube size 3 mm × 8 in.

Supelco

1,4-Dioxane solution, NMR reference standard, 5 mM in benzene-d₆ (99.6 atom % D), NMR tube size 3 mm × 8 in.

Sigma-Aldrich

1,4-Dioxane solution, NMR reference standard, 40% in benzene-d₆ (99.6 atom % D)

Supelco

1,4-Dioxane solution, NMR reference standard, 5 mM in chloroform-d (99.8 atom % D), NMR tube size 3 mm × 8 in.

Sigma-Aldrich

1,4-Dioxane, JIS special grade, ≥99.0%

Sigma-Aldrich

1,4-Dioxane, ReagentPlus^®, ≥99%, contains ≤25 ppm BHT as stabilizer

Sigma-Aldrich

1,4-Dioxane, ACS reagent, ≥99.0%

Supelco

1,4-Dioxane solution, certified reference material, 2000 μg/mL in methanol, ampule of 1 mL

Sigma-Aldrich

1,4-Dioxane, ACS reagent, ≥99.0%, contains ≤25 ppm BHT as stabilizer

Sigma-Aldrich

1,4-Dioxane, puriss. p.a., ACS reagent, reag. ISO, reag. Ph. Eur., ≥99.5% (GC)

Sigma-Aldrich

1,4-Dioxane, suitable for HPLC, ≥99.5%

Sigma-Aldrich

Malononitrile, ≥99%

Sigma-Aldrich

Malononitrile, Arxada quality, ≥99.0% (calculated, GC, KF)