Microwave-Assisted Synthesis of Fluorescent 8-Aryl-7-deazaguanines

Abstract

Microwave-assisted conditions were adapted to our previously published synthesis of 8-aryl-7-deazaguanines via cyclocondensation of phenacyl bromides with 2,4-diamino-6-hydroxypyrimidine in refluxing 1,4-dioxane. Upon microwave irradiation at 150–225 °C, 8-aryl-7-deazaguanines were obtained in high yield above 90% and within 15–60 min, compared to the 24–72 h that are required under reflux conditions. Three new fluorescent 8-heteroaryl-7-deazaguanines were additionally produced and characterized confirming our hypothesis that compounds of this class typically exhibit fluorescence properties, regardless of the aryl substituent.

Key words

fluorescent - 7-deazaguanines - phenacyl bromides - 2,4-diamino-6-hydroxypyrimidine - microwave-assisted synthesis

• References and Notes

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• 19 Procedure 2 mmol of 2,4-diamino-6-hydroxypyrimidine, 2 mmol of substituted phenacyl bromide, 2 mmol of triethylamine, and 10 mL of 1,4-dioxane were charged in a 35 mL MW vial equipped with a stir bar. The vial was heated at the assigned reaction time (15–60 min) and temperature (150–225 °C). Upon cooling to room temperature, the reaction mixture was decanted, and 1,4-dioxane was carefully removed. The residual slurry was treated with 30 mL of water and stirred vigorously until a fine solid precipitated. The 1,4-dioxane phase was evaporated and treated with 15 mL of water until a fine solid precipitated. The combined solid product was filtered under vacuum, washed with 3 × 20 mL of water, and dried under vacuum. Subsequently, the isolated product was dried in an oven at 85 °C for a minimum of 8 h and was characterized via NMR spectroscopy and mass spectroscopy. Analytical samples of the isolated products were purified according to the following methods.
• 20 An analytical sample of the product (3b, 3c, 3e, or 3i, 100 mg) was dissolved in 1 mL of DMSO. The solution was triturated with water to precipitate the product, which was isolated via filtration under vacuum. Products were isolated in 40–50% yield.
• 21 An analytical sample of the product (3a, 3d, 3g, or 3h, 100 mg) was dissolved in 1 mL of DMSO and loaded on top of a silica gel column, which was subsequently equilibrated with ethyl acetate. The product was eluted with a gradient of 0–30% methanol in ethyl acetate. The fractions containing the product were evaporated under vacuum. The resulting residue was triturated with water to precipitate the product, which was isolated via filtration under vacuum. Products were isolated in 30–40% yield.
• 22 2-Amino-6-(2-thiophenyl)-3,7-dihydro-pyrrolo[2,3-d]pyrimidin-4-one (3g) ¹H NMR (500 MHz, DMSO-d ₆): δ = 11.57 (s, 1 H), 10.34 (s, 1 H), 7.32 (m, 2 H), 7.00 (d, 1 H, J = 8 Hz), 6.39 (d, 1 H, J = 2 Hz), 6.18 (s, 2 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 158.5, 152.8, 152.4, 135.6, 127.8, 124.7, 123.3, 121.8, 101.0, 98.9. HRMS: m/z calcd for MH⁺: 233.04916; found: 233.04959.
• 23 2-Amino-6-(3-thiophenyl)-3,7-dihydro-pyrrolo[2,3-d]pyrimidin-4-one (3h) ¹H NMR (500 MHz, DMSO-d ₆): δ = 11.42 (s, 1 H), 10.27 (s, 1 H), 7.62 (d, 1 H, J = 5 Hz), 7.52 (s, 1 H), 7.47 (d, 1 H, J = 5 Hz), 6.54 (d, 1 H, J = 0.5 Hz), 6.12 (s, 2 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 158.7, 152.6, 152.2, 134.1, 126.6, 126.4, 125.5, 116.9, 100.8, 98.9. HRMS: m/z calcd for MH⁺: 233.04916; found: 233.04955.
• 24 2-Amino-6-(2-benzofuranyl)-3,7-dihydro-pyrrolo[2,3-d]pyrimidin-4-one (3i) ¹H NMR (500 MHz, DMSO-d ₆): δ = 11.83 (s, 1 H), 10.45 (s, 1 H), 7.58 (d, 1 H, J = 7.5 Hz), 7.54 (d, 1 H, J = 7.5 Hz), 7.23 (t, 2 H, J = 7.5 Hz), 7.06 (s, 1 H), 6.69 (s, 1 H), 6.29 (s, 2 H). ¹³C NMR (125 MHz, DMSO-d ₆): δ = 158.6, 153.7, 153.2, 153.0, 149.7, 128.9, 123.8, 123.2, 120.9, 120.5, 110.7, 101.2, 100.9, 99.2. HRMS: m/z calcd for MH⁺: 267.08765; found: 267.08794.
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