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DOI: 10.1055/s-0030-1258768
Copper(I)-Catalyst-Free Approach for the Synthesis of Chromene-Fused Pyrido[3,2-d]pyrimidines by Lewis Acid Catalyzed Aza-Diels-Alder Reaction
Publication History
Publication Date:
30 September 2010 (online)
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Abstract
Pyrido[3,2-d]pyrimidine derivatives have been synthesized by the hetero-Diels-Alder reaction of 5-amino-1,3-dimethyl uracil and O-propargylated salicylaldehyde. The reaction requires only a single-step operation and provides potentially bioactive polycyclic heterocycles in high yields (71-82%) from easily available starting materials.
Key words
aza-hetero-Diels-Alder reaction - Lewis acid catalysis - Schiff base - Pyrido[3,2-d)]pyrimidine - 5-amino-1,3-dimethyl uracil
- Supporting Information for this article is available online:
- Supporting Information
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References and Notes
Compound 4a
A
mixture of 5-amino-1,3-dimethyl uracil (3,
50 mg, 0.322 mmol) and O-propargyl salicylaldehyde (2a,
70 mg, 0.322 mmol) was stirred in toluene at r.t. for 10 min. After
addition of 10 mol% BF3˙OEt2 (mol% calcd
relative to the amine) the reaction mixture was refluxed for 4 h.
After completion of the reaction as monitored by TLC the reaction
mixture was cooled and diluted with sat. NaHCO3 solution
(50 mL). This was extracted with EtOAc (3 × 25
mL). The combined organic extract was washed with brine and dried
over Na2SO4. The solvent was distilled off.
The resulting crude product was purified by column chromatography
over silica gel (60-120 mesh) using hexane-EtOAc
mixture (1:4) as eluent to give the compound 4a.
Yield 82%; colorless
solid; mp above 290 ˚C. IR (KBr): νmax = 1705,
1657, 1502, 1478 cm-¹. ¹H
NMR (400 MHz, CDCl3): δ = 1.38
(s, 9 H), 3.55 (s, 3 H), 3.60 (s, 3 H), 5.27 (s, 2 H), 6.91 (d, J = 8.4 Hz,
1 H), 7.30 (s, 1 H), 7.39 (dd, J = 2.4,
8.4 Hz, 1 H), 8.38 (d, J = 2.4
Hz, 1 H) ppm. ¹³C NMR (100 MHz, CDCl3):
29.0, 30.7, 31.4 (3 C), 67.7, 116.6, 116.7, 117.8, 121.0, 121.7,
129.2, 131.5, 132.7, 136.9, 145.4, 145.9, 150.1, 153.9 ppm. HRMS: m/z calcd for C20H21N3O3 [M + H]+:
352.1656; found: 352.1641;
Compound
4c
Yield 75%; colorless solid; mp above 290 ˚C.
IR (KBr): νmax = 1707,
1663, 1504, 1481 cm-¹. ¹H
NMR (400 MHz, CDCl3): δ = 3.56
(s, 3 H), 3.63 (s, 3 H), 3.90 (s, 3 H), 5.26 (s, 2 H), 6.92 (d, J = 1.6 Hz,
2 H), 7.33 (s, 1 H), 7.89 (s, 1 H) ppm. MS: m/z = 325 [M+].
Anal. Calcd. for C17H15N3O4:
C, 62.76; H, 4.65; N, 12.92. Found: C, 62.95; H, 4.61; N, 12.85.