Category: 13445-16-4

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

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

Adding a certain compound to certain chemical reactions, such as: 13445-16-4, 3-Bromo-2,6-dimethoxypyridine, can increase the reaction rate and produce products with better performance than those obtained under traditional synthetic methods. Here is a downstream synthesis route of the compound, Quality Control of 3-Bromo-2,6-dimethoxypyridine, blongs to pyridine-derivatives compound. Quality Control of 3-Bromo-2,6-dimethoxypyridine

Preparation 7 (Z,E)-Ethyl 3-(2,6-dimethoxypyridin-3-yl)-3-ethoxyacrylate Bis(tri-t-butylphosphine)palladium (47 mg, 0.092 mmol)) and lithium chloride (292 mg, 0.27 mmol) were added to a flask equipped with reflux condenser, and the apparatus was evacuated under vacuum and refilled with N2 several times. To this flask was added via cannula a degassed solution of anhydrous 1,4-dioxane (8 mL) under N2, followed by 3-bromo-2,6-dimethoxypyridine (500 mg, 2.29 mmol), N,N-dicyclohexylmethylamine (540 uL, 2.52 mmol) and ethyl 3-ethoxyacrylate (1.0 mL, 6.88 mmol), and the resulting orange solution was heated to 110 C. After 20 hours, the reaction mixture was cooled to room temperature, quenched with water and diluted with EtOAc. The layers were separated and the aqueous layer was extracted with EtOAc. The combined organic extracts were washed with brine, dried over Na2SO4 and concentrated in vacuo. The residue was purified by chromatography on silica eluting with 0-50% EtOAc/heptane to yield the title compound (604 mg, 94%) as an amber oil. 1H NMR showed the product to be composed of a 2.5:1 mixture of E/Z isomers.

At the same time, in my other blogs, there are other synthetic methods of this type of compound,13445-16-4, 3-Bromo-2,6-dimethoxypyridine, and friends who are interested can also refer to it.

Reference:
Patent; Carpino, Philip A.; Conn, Edward L.; Dow, Robert L.; Dowling, Matthew S.; Hepworth, David; Kung, Daniel Wei-Shung; Orr, Suvi; Rocke, Benjamin N.; Ruggeri, Roger B.; Sammons, Matthew F.; Warmus, Joseph S.; Zhang, Yan; US2013/123230; (2013); A1;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem

In the next few decades, the world population will flourish. As the population grows rapidly and people all over the world use more and more resources, all industries must consider their environmental impact. 13445-16-4, name is 3-Bromo-2,6-dimethoxypyridine, the common compound, a new synthetic route is introduced below. SDS of cas: 13445-16-4

EXAMPLE 1 Preparation of 2,6-dimethoxy-3-bromo-4-(diphenylphosphino)pyridine To a magnetically stirred solution of 4.0 mL of approximatly 2.0M LDA solution (in hexane) (7.98 mmol) was added a solution of 2,6-dimethoxyl-3-bromopyridine (3.14 g, 6.14 mmol) in 10 mL of THF at -78 C. over a period 20 minutes while the internal temperature was kept below -78 C. To the resulting red-brown suspension was added a solution of chlorodiphenylphosphine (1.20 mL, 6.75 mmol) in the 10 mL of THF at -78 C. The reaction mixture was allowed to warm to ambient temperature overnight and was poured into 20 mL water. The organic product was extracted with dichloromethane (3*20 mL). The combined extract was dried with anhydrous magnesium sulfate and was concentrated in vaccuo to give a crude product which was recrystallized in methanol to give 2.34 g of pure product (95% theoretical yield). 1 H-NMR(400 MHz): delta 3.83 (s, 3H, OCH3), 4.00 (s, 3H, OCH3), 5.71 (d, JPH =2.4 Hz, 1H, PyH’s), 7.38~7.28 (m, 10H, PhH’s). 31 P-NMR(161 MHz): delta-4.18 ppm. 13 C-NMR(101 MHz): delta 53.61, 54.48, 101.73 (J=27.8 Hz), 106.52 (J=2.1 Hz), 128.76 (J=7.6 Hz), 129.38, 134.07, 134.27, 134.33, 134.43, 154.13 (J=16.0 Hz), 158.62 (J=5.6 Hz), 161.5. mass spectrum (high resolution): M.W.=401.0, consistent with C19 H17 NPBrO2, melting point: 149.7~150.8 C.

The synthetic route of 13445-16-4 has been constantly updated, and we look forward to future research findings.

Reference:
Patent; The Hong Kong Polytechnic University; US5886182; (1999); A;,
Pyridine – Wikipedia,
Pyridine | C5H5N – PubChem