2,6-Dibromo-3-pyridinamine

Brown powder

Method F; Example F-1; 4-({6-Bromo-2-oxo-1-[2-(trifluoromethyl)benzyl]-2, 3-dihydro-1 H-pyrido[2, 3- b][1 , 4]thiazin-3-yl}methyl)benzoic Acid; Preparation of F-1-a 2, 6-Dibromopyridin-3-amine; As suggested in Majumdar, K. C; Mondal, S. Regioselective synthesis of substituted pyrrolopyridines based on Pd(ll)-mediated cross coupling and base induced heteroannulation. Tet. Letters 2007, 48, 6951-6953, to a solution of 3-aminopyridine (4.75 g, 50.5 mmol) in DMSO (100 ml_) and water (2.5 ml_) at 0500ml round bottom flask, 3-aminopyridine (25.0g, 0.226mol), dimethyl sulfoxide(250ml), water (5ml) were placed in a 0 ° C N- bromosuccinimide (99.3g, 0.558mol)little by little the scored. The reaction solution was stirred at room temperature for 24 hours and recrystallizedacetonitrile was obtained [Intermediate 2-b]. (59g, 89percent)Synthesis of 2, 6-dibromopyridin-3-amine [0310] To a stirred solution of pyridine-3 -amine (20.0 g, 0.21 mol) in CC1To a stirred solution of pyridin-3-amine (20.0 g, 0.21 mol) in CClSynthesis of 2, 6-dibromopyridin-3-amine (0972) To a stirred solution of pyridin-3-amine (20.0 g, 0.21 mol) in CClSodium methoxide (176.2 g, 3.26 mol) was added in portions to a sol. of 3-amino-2, 6- dibromopyridine (100 g, 939 mmol) in 1, 4-dioxane (1 1) and the r.m. was stirred under reflux for 3 h. After cooling, the r.m. was poured onto a sat. aq. NH4C1 aq. sol (1 1). Additional NH4CI (150 g) and H20 (1 1) were added and the r.m. was stirred at r.t. for 30 min. Et20 (2 1) was added and the r.m. was stirred for 30 min. The layers were separated and the aq. layer was diluted with H20 (1.5 1) and further extracted with Et20 (6 x 0.5 1). The combined o.l. were treated with brine (2 x 0.5 1), dried (MgS04) and cone, under reduced pressure to give a black residue. The residue was purified by flash chromatography over silicagel (glas filter, eluent DCM). The product fractions were combined and cone, under reduced pressure to afford an orange-brownish solid residue. Yield: 67.2 g of intermediate 24 (78.3 %).Synthesis of 6-bromo-2-methoxypyridin-3-amine [0311] To a stirred solution of 2, 6-dibromopyridin-3 -amine (38 g, 0.15 mol) in 1, 4- dioxane (400 mL) under argon atmosphere was added sodium methoxide (70.55 g, 1.30 mol) and stirred at reflux for 8 h. After consumption of the starting materials (monitored by TLC), the reaction was quenched with ice cold water (200 mL) and extracted with EtOAc (3 x 200 mL). The combined organic extracts were washed with cold water (2 x 100 mL), dried over sodium sulfate and concentrated in vacuo. The crude material was purified through silica gel column chromatography using 10% EtOAc:hexanes to afford 6-bromo-2-methoxypyridin-3- amine (13 g, 42%) as an off-white solid. 1H-NMR (CDC13, 400 MHz): delta 6.87 (d, 1H), 6.76 (d, 1H), 4.01 (s, 3H), 3.75 (bs, 2H); TLC: 20% EtOAc:hexane (R/. 0.5).To a stirred solution of 2, 6-dibromopyridin-3-amine (38 g, 0.188 mol) in 1, 4- dioxane (400 mL) under an argon atmosphere was added sodium methoxide (70.55 g, 1.30 mol) at room temperature. The reaction mixture was stirred at reflux for 8 h. After consumption of the starting material (monitored by TLC), the reaction mixture was quenched with ice cold water (200 mL) and extracted with EtOAc (3 x 200 mL). The combined organic extracts were washed with cold water (2 x 100 mL), dried over sodium sulfate and concentrated in vacuo. The crude material was purified by column chromatography using 10% EtOAc:hexanes to afford 6-bromo-2-methoxypyridin-3-amine (13 g, 42%) as a brown solid. 1H-NMR (CDCl3, 400 MHz): delta 6.87 (d, 1H), 6.76 (d, 1H), 4.01 (s, 3H), 3.75 (br s, 2H); TLC: 20% EtOAc:hexane (Rf: 0.5).Synthesis of 6-bromo-2-methoxypyridin-3-amine To a stirred solution of 2, 6-dibromopyridin-3-amine (38 g, 0.188 mol) in 1, 4-dioxane (400 mL) under an argon atmosphere was added sodium methoxide (70.55 g, 1.30 mol) at room temperature. The reaction mixture was stirred at reflux for 8 h. After consumption of the starting material (monitored by TLC), the reaction mixture was quenched with ice cold water (200 mL) and extracted with EtOAc (3*200 mL). The combined organic extracts were washed with cold water (2*100 mL), dried over sodium sulfate and concentrated in vacuo. The crude material was purified by column chromatography using 10% EtOAc:hexanes to afford 6-bromo-2-methoxypyridin-3-amine (13 g, 42%) as a brown solid. 1H-NMR (CDCl3, 400 MHz): delta 6.87 (d, 1H), 6.76 (d, 1H), 4.01 (s, 3H), 3.75 (br s, 2H); TLC: 20% EtOAc:hexane (Rf: 0.5).

Molecular Weight:251.91
XLogP3:2.2
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:251.87207
Monoisotopic Mass:249.87412
Topological Polar Surface Area:38.9
Heavy Atom Count:9
Complexity:99
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes