Preparation and application of 3,5-dimethylisoxazole-4-boronic acid pinacol ester_Industrial additives

Preparation and application background of 3,5-dimethylisoxazole-4-boronic acid pinacol ester

3,5-Dimethylisoxazole-4-boronic acid pinacol ester can be used as a pharmaceutical synthesis intermediate, which can be used with 4-iodo-3,5-dimethoxyisoxazole and 4,4 , 5,5-tetramethyl-1,3-dioxaborane was prepared by reaction. 3,5-Dimethylisoxazole-4-boronic acid pinacol ester is often used to perform metal-catalyzed coupling reactions, such as Suzuki reactions.

Preparation and application of 3,5-dimethylisoxazole-4-boronic acid pinacol ester

To 4-iodo-3,5-dimethoxyisoxazole (3.56 g, 16 mmol), TEA (6.68 ml, 48 mmol), Pd(PPh₃)₂Cl₂ (0.56 g, 0.8 mmol, 5% catalyst) in dioxane (30 ml), 4,4,5,5-tetramethyl-1 was added, 3 – Dioxaborane (4.06 ml, 24 mmol), reflux for 3 hours. The solvent was then removed under reduced pressure, diethyl ether (50ml) was added and filtered through a plug of silica. Reduce the solvent to half its volume and wash with water (20 ml), brine (20 ml), dry (MgSO₄) and evaporate to dryness. The product was then purified by column chromatography (10% Et₂O in hexane) to give 3,5-dimethylisoxazole-4-boronic acid pinacol ester as a white color Crystalline solid (2.35 g, 66%). mp 99-101°C; νmax(thin film)/cm^-1 1594, 1401, 1073 (isoxazole); ¹H NMR (CDCl_{3, 250MHz); δ 1.30 (s, 12H, 4 x CH3), 2.33 (s, 3H, ArCH3), 2.51 (s, 3H, ArCH3); ¹³C NMR (CDCl3, 63MHz): δ 12.1, 13.2, 25.2, 83.7, 164.2, 178.3; Found C, 58.98, H, 8.07, N, 6.18, C11H18BNO3 requires C, 59.23, H, 8.13, N, 6.28.}

Preparation and application of 3,5-dimethylisoxazole-4-boronic acid pinacol ester

3,5-Dimethylisoxazole-4-boronic acid pinacol ester can be prepared by Suzuki reaction to prepare 6-(3,5-dimethylisoxazole)-4-phenyl-3-(( 1-phenyl-1H-1,2,3-triazol)methyl)-3,4-dihydroquinazolin-2(1H)-one. Here’s how:

6-Bromo-4-phenyl-3-((1-phenyl-1H-1,2,3-triazole)methyl)-3,4-dihydroquinazoline-2( 1H)-ketone (0.24g, 0.52mmol), 3,5-dimethylisoxazole-4-boronic acid pinacol ester (0.23g, 1.04mmol), [1,1′-bis(diphenylphosphine) ) Ferrocene]palladium dichloride dichloromethane complex (0.038g, 0.052mmol) and potassium carbonate (0.144g, 1.04mmol) dissolved in 1ml N, N-dimethylformamide, 1ml methanol and 3ml toluene Under nitrogen protection, heat the mixture to 70°C and stir for 24 hours. Add 10 ml of water and 10 ml of ethyl acetate. Filter the solution through diatomaceous earth. Collect the filtrate and extract with ethyl acetate. Collect the organic layer and add anhydrous sodium sulfate. Dry, evaporate the organic solvent under reduced pressure, and the residue is purified by silica gel column chromatography, using petroleum ether/ethyl acetate (V/V=2/1-1/1) to elute to obtain 6-(3,5-bis Methylisoxazole)-4-phenyl-3-((1-phenyl-1H-1,2,3-triazole)methyl)-3,4-dihydroquinazoline-2(1H )-ketone 0.13g, white solid, yield 52.32%. ¹HNMR (300MHz, DMSO) δ9.76 (s, 1H), 8.72 (s, 1H), 7.88 (d, J=7.5Hz, 2H), 7.58 (s, 2H), 7.42 (tt, J=14.8, 7.5Hz, 5H), 7.29 (d, J=6.9Hz, 1H), 7.19 (s, 1H), 7.13 (d, J=8.2Hz, 1H), 6.92 (d, J= 8.2Hz, 1H), 5.77 (s, 1H), 5.27 (d, J=15.4Hz, 1H), 3.93 (d, J=15.4Hz, 1H), 2.27 (s, 3H), 2.10 (s, 3H) .

References

[1] Gutierrez C D , Bavets Polycarbonateias V , Mcdonald E . ClTi(O i Pr) 3 -Promoted Reductive Amination on the Solid Phase: Combinatorial Synthesis of a Biaryl-Based Sulfonamide Library Deuterated Tetrahydrofuran[J] . Journal of Combinatorial Chemistry, 2008, 10(2):280-284.

[2]CN201511016420.X Preparation method of triazole derivatives and their use as drugs