Electric Literature of 13445-16-4 , The common heterocyclic compound, 13445-16-4, name is 3-Bromo-2,6-dimethoxypyridine, molecular formula is C7H8BrNO2, its traditional synthetic route has been very mature, but the traditional synthetic route has various shortcomings, such as complicated route, low yield, poor purity, etc., below Introduce a new synthetic route.
Step 2: Preparation of (3aR,4R,6S,6aS)-4-(((tert-butyldimethylsilyl)oxy)methyl)-6-(2,6- dimethoxypyridin-3-yl)-2,2-dimethyltetrahydro-3aH-[l,3]dioxolo[4,5-c] (17d) To a stirred solution of 3-bromo-2,6-dimethoxypyridine (17b) (2.73 g, 12.50 mmol) in Tetrahydrofuran (30 mL) was added n-Butyl lithium (1.6 M solution in hexanes, 7.81 mL, 12.50 mmol) at -78 C and stirred at the same temperature for 1 hr. To the anion formed at – 78 C was added a freshly prepared solution of (3aR,4R,6aS)-4-((tert- butyldimethylsilyloxy)methyl)-2,2-dimethyl-4,6a-dihydro-3aH-[l,3]dioxolo[4,5-c]pyrrole (lk) (2.85 g, 10 mmol) in toluene (1.2 molar solution) over a period of 15 minutes. The reaction stirred for 30 minutes at -78 C, quenched with water (50 mL) and extracted with ethyl acetate (3 x 100 mL). The combined organic layers were washed with water (50 mL), brine (50 mL) dried, filtered and concentrated in vacuum. The crude residue was purified by flash column chromatography (silica gel 40 g, eluting with 0-100% ethyl acetate in hexanes) to afford (3aR,4R,6aS)-4-((tert-butyldimethylsilyloxy)methyl)-6-(2,6-dimethoxypyridin-3- yl)-2,2-dimethyltetrahydro-3aH-[l,3]dioxolo[4,5-c]pyrrole (17d) (1.35 g, 31.8 % yield) as a light brown syrup. 1H NMR (300 MHz, DMSO-d6) delta 7.64 (d, J = 8.1 Hz, 1H), 6.29 (d, J = 8.0 Hz, 1H), 4.42 – 4.28 (m, 2H), 4.09 (d, J = 4.3 Hz, 1H), 3.82 (s, 3H), 3.79 (s, 3H), 3.57 (d, J = 5.0 Hz, 2H), 3.05 (d, J = 4.8 Hz, 1H), 2.85 (s, 1H, D20 exchangeable), 1.40 (s, 3H), 1.17 (s, 3H), 0.82 (s, 9H), -0.00 (d, J= 1.3 Hz, 6H). Mass spec (ES+) 425.1 (M+l).
The synthetic route of 13445-16-4 has been constantly updated, and we look forward to future research findings.
Reference:
Patent; BIOCRYST PHARMACEUTICALS, INC.; BABU, Yarlagadda, S.; KOTIAN, Pravin, L.; BANTIA, Shanta; WU, Minwan; KUMAR, V., Satish; WO2014/78778; (2014); A2;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem