5-Bromo-3-(trifluoromethyl)pyridin-2-amine

Step 3) 5-Bromo-3-trifluoromethyl-pyridin-2-ylamine CAS-No. [79456-34-11; To a solution of the above 3-trifluoromethyl-pyridin-2-ylamine (16.21 g, 100 mmol) in acetonitrile (300 mL) at 5° C. was added NBS (17.8 g, 100 mmol) and the mixture was stirred at 23° C. for 1 h. Poured into ice and additional sat. NaHCOExample 46; Preparation of iV-(5-(6-Amino-5-(trifluoromethyl)pyridin-3- yl)thiazolo [5, 4-] pyrimidin-2-yl)acetamide (46); 46C 43D Example 46[0428] To a solution of 3-(trifluoromethyl)pyridin-2-amine (46A, 2.10 g, 13 mmol) in acetonitrile (40 mL) was added N-bromosuccinimide (2.54 g, 14.2 mmol). The mixture was stirred overnight at room temperature. The reaction mixture was poured into water (50 mL) and extracted with ethyl acetate (100 mL x 2). The organic extract was washed with brine (50 mL) and dried over anhydrous MgSOCompound BB-21-1 (42.0g, 259mmol) was dissolved in N, N - dimethylformamide (400mL), then was addedN - bromosuccinimide (46.1g, 259mmol).The reaction was stirred at 20 2 hours.The reaction solution was poured into stirred5percent mixture of sodium bisulfite and water (10:1), the precipitate was filtered, washed with water, dissolved in methylene chloride (a 500 mL), dried over sodium sulfatedrying, filtered, and concentrated to give the title compound BB -20-2 (yellow solid, 51.0g, yield: 89.7percent).2-Amino-3-trifluoromethyl pyridine (5.4 gm, 33.3 mmol) was dissolved in DMF (31 mL) and N-bromosuccinimide (5.9 gm, 33.3 mmol) dissolved in DMF (31 mL) was added N-bromosuccinimide (20.83g, 117.28 mmol) was portion wise added to a stirred solution of 3-(trifluoro- methyl)pyridin-2-amine (19g, 117.28 mmol) in MeCN (380 mL) at 0°C. The RM was stirred for4h at RT. The RM was quenched with aq. NaHCO3 solution (pH—8) and then filtered. The solid was washed with water (200 mL), and the product was dissolved with EtOAc (300 mL). The organic layer was dried over anhydr. Na2SO4, filtered and solvent was concentrated under reduced pressure to give 5-bromo-3-(trifluoromethyl)pyridin-2-amine (25g, 88percent) as a solid.To a solution of 2-amino-3~trifluoromethylpyridine (100 g, 0.62 mol) in D F (500 mL) was added a solution of NBS (1 10 g, 0, 62 mol) in DMF (500 mL) dropwise at room temperature. The solution was stirred at room temperature for 2 hours and then concentrated to 300 mL. The residue was added slowly to the beaker containing a mixture of 5percent aqueous NaHS0l-ll-β-Chloro-6-furan-3-yl-8Arifluoromethyl4midazoll, 2-a]pyridine-2-carbonyl)-piperidin-4- yl]-pyrrolidin-2-one (Compound 101) Step l 5-Bromo-3-trifluoromethyl-pyridin-2-ylamine[0102] A solution of N-Bromosuccinimide (54.89 g, 308.41 mmol) in DMF (250 niL) was rapidly added dropwise via addition funnel to a stirring solution of 2-Amino-3-(trifluoromethyl) pyridine (50.00 g, 308.41 mmol) in DMF (250 mL) at room temperature. The mixture was stirred for 2 hours, concentrated to a volume of 200 mL and added slowly into a beaker containing a cold stirring mixture of 5percent NaHSOThe 3 - (trifluoromethyl) pyridin-2-amine (1.0g, 6 . 17mmol) dissolved in acetonitrile (30 ml) in, then dropped to 0 °C, then the NBS (1.2g, 6 . 74mmol) is slowly added to the system, is omitted, the temperature is increased to 25 °C reaction 2 hours. The concentrated, the residue by silica gel column chromatography (PE:EA=5:1) purification, to obtain the title compound (1.25g, yield 84.1percent).3-(Trifluoromethyl)-2-pyridinamine (150 g) was added to acetic acid (1500 mL) and stirred the mass for 10 to 15 min. Bromine (47.54 mL) was added to the mixture over a period of 45-60 min at 25-30°C. The reaction mass was maintained under stirring at 25-30°C for 2-3 h. After completion of the reaction, the mass was cooled to 10 to 15°C and diluted with water (2500 mL) subsequently neutralized the mass with solid sodium carbonate (420 g). The reaction mass was filtered and bed was washed with water (300 mL) and dried at 25 to 30°C for 12 h. The dried mass was dissolved in ethyl acetate (2250 mL) and washed with 5percent sodium bicarbonate solution (750 mL). The separated organic layer was washed with 10percent sodium chloride solution (750 mL). Clean organic layer was distilled out completely to obtain the title compound (183 g). Yield: 82percent Purity: 99.52percent 1H NMR (300 MHz, DMSO- To a solution of 3-(trifluoromethyl)pyridin-2-amine (5.4 g, 33.3 mmol) in acetonitrile (100 mL) was added NBS (5.93 g, 33.3 mmol) at OeC and reaction mixture was stirred at 25eC for 1H. After completion of the reaction, reaction mixture was quenched with saturated sodium bicarbonate (25 mL) and extracted with EtOAc (25 mL/13). The combined organic phase was washed with brine (20 mL), dried over Na2S04, filtered. The filtrate was rotary evaporated and residue was purified by flash column chromatography (silica gel) to afford 6.5 g (81percent) of the titled product. 1HNMR (400 MHz, DMSO-d6) U8.28 (d, J = 2.4 Hz, 1H), 7.91 (d, J = 2.4 Hz, 1H), 6.72 (s, 2H); ESI-MS (m/z) 241.08 (MH)3-(trifluoromethyl)pyridin-2-amine (20 g, 123 mmol) was stirred in acetic acid (200 ml) at RT. Bromine (19.72 g, 123 mmol) was added drop wise with stirring. The reaction mixture was stirred for 2 h; followed by dilution with water. The product was extracted with ethyl acetate. Organic layer was washed with water, dried over sodium sulfate and concentrated to obtain the title product in 74percent yield.Synthesis of 5-bromo-3-trifluoromethyl-pyridin-2-ylamine

Molecular Weight:241.01
XLogP3:2.1
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:5
Exact Mass:239.95100
Monoisotopic Mass:239.95100
Topological Polar Surface Area:38.9
Heavy Atom Count:12
Complexity:161
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes