3-Bromo-5-fluoro-2-pyridinamine

Procedure C: Alternatively the bromination was performed by employing H4-1 a 4-2a [0252] Alternatively the bromination was performed by employing HTo a solution of 5-fluoropyridin-2-amine (6 g, 53.52 mmol) in acetonitrile (120 mL) was added slowly NBS (12.64 g, 69.60 mmol), and the mixture was stirred at rt for 2 h, then concentrated in vacuo to dry. The residue was purified by silica gel column chromatography (PE/EA (v/v) = 20/1) to give the title compound as a yellow solid (5.4 g, 53percent).MS (ESI, pos.ion) m/z: 193.O[M+H]1H NMR (400 MHz, CDC13) (ppm): 7.95 (d, J = 2.5 Hz, 1H), 7.52 (dd, J = 7.3, 2.6 Hz, 1H), 4.84 (s, 2H).NBS (10 g, 56.2 mmol) was added slowly to a solution of 5-fluoro-pyridin-2- ylamine (12.4 g, 56.2 mmol) in MeCN (200 mL). The reaction mixture was stirred at RT overnight. After completion, the solution was filtered and the filtrate was concentrated to get a residue, which was purified by silica gel chromatography to give the product (5.2 g, 31percent) as a yellow solid.NBS (10 g, 56.2 mmol) was added slowly to a solution of 5-fluoro-pyridin-2- ylamine (55) (12.4 g, 56.2 mmol) in MeCN (200 mL). The reaction mixture was stirred at RT overnight. After completion, the solution was filtered and the filtrate was concentrated to obtain a residue, which was purified by silica gel chromatography (10percent> to 20percent> EtOAc in petroleum ether) to give 3-bromo-5-fluoro-pyridin-2-ylamine (56) (5.2 g, 27.2 mmol, 31percent> yield) as a yellow solid.ESI-MS (M+l): 191 calc. for CDescription 18 (D18); 3-bromo-5-fluoro-2-pyridinamine; To a stirred solution of 2-amino-4-fluropyridine (22.5 g, 0.20 mol) in acetonitrile (400 ml_) at -10C was added N-bromosuccinimide (37.9 g, 0.21 mol) portionwise over 15 min. Reaction mixture was allowed to stir at this temperature for 1 .5 h and at room temperature for a further 1 h. Ethyl acetate (200 ml_) added and the reaction mixture filtered to remove solids. The filtrate was concentrated in vacuo, triturated with ethyl acetate (300 ml_) and filtered the cake was washed with ethyl acetate (2 x 100 ml_). The filtrate washed with 1 M sodium hydroxide (100 ml_), water (50 ml_) and then brine (50 ml_). The combined organics were dried over sodium sulfate and solvent removed in vacuo yielding a solid. Material purified by column chromatography eluting with 25percent ethyl acetate in hexane. The relevant fractions were combined and solvent removed in vacuo yielding a light brown solid (20.4 g) which was recrystallised from hexane to furnish the title compound (10.8 g, 28percent).A 2-amino-3-bromo-4-fluoro-pyridine (0.5 g, 2.6 mmol), N-[4-(trimethylsilyl)but-3-yn-1-yl]acetamide (1.2 g, 2.5 eq.), Pd(dppf)Cl2·CH2Cl2 (103 mg, 0.048 eq.), LiCl (111 mg, 1eq.), Na2CO3 (0.56 g, 2eq.) were dissolved in anhydrous DMF (12 ml) and sealed under argon. The reaction mixture was irradiated in a microwave oven at 130C (150W) for 30 minutes. After cooling to room temperature the reaction mixture was poured to water (100 ml) and extracted with diethyl ether (2x 50 ml). The combined ether extracts were washed with water (3x 100), brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. Product was purified using column chromatography SiO2/ CHCl3:MeOH 9:1. A dark brown oil of N-{2-[5-fluoro-2-(trimethylsilyl)-1H-pyrrolo[2, 3-b]pyridin-3-yl]ethyl}acetamide was obtained (0.71 g, 94%). N-{2-[5-fluoro-2-(trimethylsilyl)-1H-pyrrolo[2, 3-b]pyridin-3-yl]ethyl}acetamide (0.9 g, 3 mmol) and sodium hydroxide (3.7 g, 30 eq.) were dissolved in ethanol (50 ml) and the reaction mixture was heated at reflux for 72 hours. After cooling to room temperature solvent was evaporated under reduced pressure, water (100 ml) was added and the solution extracted with dichloromethane (2x 100ml). The organic phase was washed with brine, dried over anhydrous magnesium sulfate and evaporated under reduced pressure. The obtained dark brown oil was converted into a fumarate and crystallized from isopropanol. A light brown solid was obtained (0.68 g, 78%). LC-MS [M+1] = 179.20 (180.08 calcd).A pressure vial containing

Molecular Weight:191.00
XLogP3:1.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Exact Mass:189.95419
Monoisotopic Mass:189.95419
Topological Polar Surface Area:38.9
Heavy Atom Count:9
Complexity:101
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes