Preparation and application of (2-chloro-5-methoxypyridin-3-yl)boric acid_Industrial additives

Preparation and application background and overview of (2-chloro-5-methoxypyridin-3-yl)boronic acid

(2-Chloro-5-methoxypyridin-3-yl)boronic acid is an organic intermediate that can be prepared from 5-bromo-6-chloropyridin-3-ol through a two-step reaction. (2-Chloro-5-methoxypyridin-3-yl)boronic acid, as a boric acid compound, is often used in metal coupling reactions.

Preparation and application of (2-chloro-5-methoxypyridin-3-yl)boronic acid

Preparation and application of (2-chloro-5-methoxypyridin-3-yl)boronic acid Step 1: Preparation of 3-bromo-2-chloro-5-methoxypyridine

Add K₂CO₃ (0.50g, 3.6mmol) followed by methyl iodide (0.20mL, 2.9mmol) to 5-bromo-6-chloropyridine- The mixture was stirred with 3-alcohol (Asymchem Laboratories, Inc., Morrisville, NC) (0.50 g, 2.4 mmol) in DMF (3.00 mL), and the mixture was sealed and heated at 45 °C for 4 h and then allowed to stand at room temperature. Leave overnight. The resulting mixture was diluted with water and the precipitate was collected and dried to give the product as a tan solid. LCMS(API-ES)m/z223(M+H)⁺;¹HNMR(MHz, CDCl₃)δ8.04(s , 1H) 7.49 (d, J = 1.37Hz, 1H) 3.86 (s, 3H).

Preparation and application of (2-chloro-5-methoxypyridin-3-yl)boronic acid Step 2: (2-chloro-5-methoxypyridin-3-yl)dimethoxy Pyridine Boric Acid

At -78°C, 2.5M n-BuLi dissolved in hexane (3.7mL, 9.3mmol) was slowly added to 3-bromo-2-chloro-5-methoxypyridine (1.73g, 7.8mmol) ) and triisopropyl borate (2.1 mL, 9.3 mmol) in THF (10.0 mL, 122 mmol) were stirred, and the resulting dark mixture was stirred at the same temperature for 1 h and then allowed to warm to room temperature over 1 h. The reaction was quenched with IN NaOH (aq) followed by some EtOAc. The separated aqueous layer was acidified with 5N HCl until the pH was about 5, and then extracted with EtOAc (x2), and the combined organic layers were washed with brine, washed with Na₂SO₄ Dry and concentrate to give 2-chloro-5-methoxypyridin-3-ylboronic acid (1.0276 g, 71%) as a brown solid. LCMS(API-ES) m/z 188(M+H)⁺.

[Nitrophenylboronic acid label:title] Application

(2-Chloro-5-methoxypyridin-3-yl)boronic acid can be used to prepare 4-(2-chloro-5-methoxypyridin-3-yl)-6-methyl-1,3 , 5-triazin-2-amine: 1,4-dioxane (10.00mL) and water (2.5mL) were added to 2-chloro-5-methoxypyridin-3-ylboronic acid (1.03g, 5.48mmol) , 4-chloro-6-methyl-1,3,5-triazin-2-amine (0.72g, 4.98mmol), Na₂CO₃ (1.32 g, 12.5 mmol) and Pd(PPh₃)₄ (0.576 g, 0.1 equiv), and the mixture was sealed and heated at 90°C overnight. After cooling, the mixture was concentrated. Flash column chromatography purification (short column, SiO₂, neat DCM to 5% MeOH in DCM) provided 4-(2-chloro-5-methoxypyridine- 3-yl)-6-methyl-1,3,5-triazin-2-amine (0.644 g, 51%). LCMS (API-ES) m/z 252 (M+H)⁺; ¹HNMR (MHz, d6-DMSO) δ8.24 (d, J＝1.17Hz , 1H) 7.68 (br.s., 2H) 7.65 (d, J = 1.17Hz, 1H) 3.87 (s, 3H) 2.36 (s, 3H).