5-Bromo-2-(dimethylamino)pyridine

General procedure: To a mixture of 2-aminopyridine (0.5 mmol, 1 equiv), p-TSA (0.4 mmol, 0.8 equiv), 1-butylpyridinium bromide (1.5 mmol, 3 equiv) in a 50 mL Schlenk tube were added 1, 2-dimethoxyethane (2 mL) under air. Then HN-Bromosuccinimide (190 mmol) was added portionwise to a solution of [2- (DIMETHYLAMINO)-PYRIDINE] (200 mmol) in DCM (1.0 L). After 10 min a HPLC- MS indicated complete conversion. The solvent was removed in vacuo and the residue was purified by flash-chromatography (ethyl acetate/heptane 1: 19) to give 25.7 g [(128] mmol, [64percent)] of the desired arylbromide as a white solid. LC-MS: rt = 0.46 min, [201] (M+1, ES+).Step 64a: 5-Bromo-N, N-dimethylpyridin-2-amine (cCompound 0601-114)To a solution of 5-bromopyridin-2-amine (1.0 g, 5.8 mmol) in THF (25 mL) was added NaH (0.92 g, 23.1 mmol) at 0 °C and stirred for 10 min. followed by the addition of CHStep 64a: 5-Bromo-N, N-dimethylpyridin-2-amine (compound 0601-114)[0486]To a solution of 5-bromopyridin-2-amine (1.0 g, 5.8 mmol) in THF (25 mL) was added NaH (0.92 g, 23.1 mmol) at 0° C. and stirred for 10 min. followed by the addition of CHTHF (25mL) in 5-bromo-2-amine (1.0g, 5.8mmol) to a solution of NaH (0.92g, 23.1mmol) was stirred addition to 10 minutes at 0 , then CH3I (1mL, 16mmol) and the mixture was stirred for 1 hour with the addition of. With the addition of water (30mL) and extracted with ethyl acetate (3x30mL). The combined organic layers were washed with brine, dried over Na2SO4, and concentrated and purified by column chromatography (petroleum ether in ethyl acetate, 10percent v / v) on silica gel to give the white solid title compound obtained as (1.1g, 94percent).2, 5-dibromopyridine (1.0 mmol), DMF (1 mmol), Sodium tert-butoxide (0.5-4.0 mmol) and 2 mL of water were successively added to a 10 mL sealed tube, and the mixture was heated and stirred for 6 hours in an oil bath at 140 ° C, and quenched with dichloromethane.When the reaction is over, The yield of the product can be determined by GC and GC-MS by adding the internal standard to the crude product.When the sodium tert-butoxide was 0.5 mmol, 1.0 mmol, 2.0 mmol, 3.0 mmol, and 4.0 mmol, the isolated yields of the products were 55percent, 66percent, 72percent, 80percent, and 82percent, respectively.37 percent Aqueous formaldehyde (13.55 ml, 180.3 mmol) was added dropwise to a solution of 2-amino-5-bromopyrydine (2.0 g, 11.56 mmol) in methanol (465 ml)at room temperature. To the mixture was added dropwise a solution of zinc chloride (3.94 g, 28.90 mmol) and sodium cyanoborohydride (3.63 g, 57.80 mmol) in methanol (155 ml)and the mixture was stirred at room temperature for 4 hrs. To the reaction mixture was added ice water (300 ml) at 5 °C and then methanol was distilled off under reduced pressure. The residue was extracted with ethyl acetate - tetrahydrofuran (1/1) and the extract was washed with water and brine in turn and dried. The solvent was distilled off under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate = 24 and 5) to give 5-bromo-2-dimethylamino-pyridine (1.00 g, 43 percent) as colorless crystals. m.p.: 39 - 41 °C; IR (Nujol): 1588 cm-1; APCI-MS m/z: 201/203 [M+H]+.(Preparation 27) (0109) 1) 37percent Aqueous formaldehyde (13.55 ml, 180.3 mmol) was added dropwise to a solution of 2-amino-5-bromopyrydine (2.0 g, 11.56 mmol) in methanol (465 ml)at room temperature. To the mixture was added dropwise a solution of zinc chloride (3.94 g, 28.90 mmol) and sodium cyanoborohydride (3. 63 g, 57.80 mmol) in methanol (155 ml) and the mixture was stirred at room temperature for 4 hrs. To the reaction mixture was added ice water (300 ml) at 5° C. and then methanol was distilled off under reduced pressure. The residue was extracted with ethyl acetate-tetrahydrofuran (1/1) and the extract was washed with water and brine in turn and dried. The solvent was distilled off under reduced pressure. The residue was purified by column chromatography on silica gel (n-hexane/ethyl acetate=24 and 5) to give 5-bromo-2-dimethylamino-pyridin- e (1.00 g, 43percent) as colorless crystals. m.p.: 39-41° C.; IR (Nujol): 1588 cmTo sealed tube was added 5-bromo-2-fluoropyridine (825 mg, 5.1 mmol), dimethylamine/water (7.0 mL, 33percent) and THF (3.0 mL), then sealed and heated to 110 °C overnight. The reaction mixture was cooled to RT and extracted with EA, the organic layers were combined and washed with brine, then dried over a2S0To a sealed tube was added 5-bromo-2-fluoropyridine (2.0 g, 1 1 .36 mmol), dimethylamine (7.0 mL, 45.6 mmol) in water and tetrahydrofuran (3 mL) and the reaction was heated to 100 °C overnight. The reaction mixture was cooled to room temperature and extracted with EtOAc (15 mL x 3), the organic layers were combined and washed with brine and dried over NaA. Example 191-1 a)

Molecular Weight:201.06
XLogP3:2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:199.99491
Monoisotopic Mass:199.99491
Topological Polar Surface Area:16.1
Heavy Atom Count:10
Complexity:106
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes