2-Amino-5-bromo-3-benzloxypyridine

2-Amino-3-benzyloxypyridine (85.0 g, 0.42 mol) was dissolved in a 10 percent aqueous solution of sulphuric acid (1000 ml). The yellow solution was cooled to 0 to 4 °C and a solution of bromine (80.5 g, 0.50 mol) in acetic acid (276 g, 4.6 mol) was added dropwise over a period of 2 hours. A red suspension was obtained which was stirred for 2.5 hours at 0 °C and was then poured onto a mixture of ice water (500 ml) and dichloromethane (1000 ml). A pH-value of 8 was adjusted by addition of 25 percent aqueous ammonia solution (approx. 600 ml) to the well-stirred biphasic mixture. The phases were separated and the aqueous phase was extracted with dichloromethane (3 x 500 ml). The combined organic phases were washed with water (400 ml) and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by flash chromatography [1 kg of silica gel, eluant : petrol ether/ethyl acetate = 7: 3 (v/v) ]. Thus, 96.0 g of the title compound were isolated in form of a brown solid (81 percent yield). Melting point: 109-110 °C 'H-NMR (CDCI3, 200 MHz): 8= 4.73 (bs, 2 H), 5.04 (s, 2 H), 7.08 (d, 1 H), 7.40 (me, 5 H), 7.73 (d, 1 H).IV. Starting Compounds and Intermediates; Synthesis ofintermediates for racemic 7H-8, 9-dihydro-pvranof2, 3-cl-imidazo ( ?, 2- alpvridines via cross metathesis; i. 2-Amino-3-benzyloxy-5-bromo-pyridine; 2-Amino-3-benzyloxypyridine (85. 0 g, 0.42 mol) was dissolved in a 10 percent aqueous solution of sulphuric acid (1000 ml). The yellow solution was cooled to 0 to 4 °C and a solution of bromine (80.5 g, 0.50 mol) in acetic acid (276 g, 4.6 mol) was added dropwise over a period of 2 h. A red suspension was ob- tained which was stirred for 2.5 h at 0 °C and was then poured onto a mixture of ice water (500 mi) and dichloromethane (1000 ml). A pH-value of 8 was adjusted by addition of 25 percent aqueous ammonia solu- tion (approx. 600 ml) to the well-stirred biphasic mixture. The phases were separated and the aqueous phase was extracted with dichloromethane (3 x 500 ml). The combined organic phases were washed with water (400 ml) and dried over sodium sulfate. The solvent was removed under reduced pressure and the residue was purified by flash chromatography [1 kg of silica gel, eluant : petrol ether/ethyl acetate = 7: 3 (v/v) ]. Thus, 96.0 g of the tide compound were isolated in form of a brown solid (81 percent yield).Example 84A Example 14A 3-(Benzyloxy)-5-bromopyridine-2-amine 200 g (1 mol) of 2-amino-3-benzyloxypyridine were initially charged in 4 l of dichloromethane, and a solution of 62 ml (1.2 mol) of bromine in 620 ml of dichloromethane was added at 0° C. over a period of 30 min. After the addition had ended, the reaction solution was stirred at 0° C. for 60 min. About 4 l of saturated aqueous sodium bicarbonate solution were then added to the mixture. The organic phase was separated off and concentrated. The residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate 6:4) and the product fractions were concentrated. This gave 214 g (77percent of theory) of the title compound. LC-MS (Method 2): RExample 236A 3-(Benzyloxy)-5-bromopyridine-2-amine [1076] 2-amino-3-benzyloxypyridine were initially charged in 4 l of dichloromethane, and a solution of 62 ml (1.2 mol) of bromine in 620 ml of dichloromethane was added at 0° C. over a period of 30 min. After the addition had ended, the reaction solution was stirred at 0° C. for 60 min. About 4 l of saturated aqueous sodium bicarbonate solution were then added to the mixture. The organic phase was separated off and concentrated. The residue was purified by silica gel column chromatography (petroleum ether:ethyl acetate 6:4) and the product fractions were concentrated. This gave 214 g (77percent of theory) of the title compound. [1078] LC-MS (Method 2): R10600] 200 g (1 mol) of 2-amino-3-benzyloxypyridine were initially charged in 4 1 of dichloromethane, and at 00 C. a solution of 62 ml (1.2 mol) of bromine in 620 ml of dichloromethane was added over 30 mi Afier the addition had ended, the reaction solution was stirred at 00 C. for 60 mm. About 4 1 of saturated aqueous sodium bicarbonate solution were then added to the mixture. The organic phase was removed and concentrated. The residue was purified by silica gel colunm chromatography (petroleum ether/ethyl acetate 6:4) and the product fractions were concentrated. This gave214 g (77percent of theory) of the title compound.10601] LC-MS (Method 1): R=0.92 mm10602] MS (ESpos): mlz=279 (M+H)10603] ‘H-NMR (400 MHz, DMSO-d5): ö=5.16 (s, 2H), 5.94-6.00 (m, 2H), 7.26-7.29 (m, 1H), 7.31-7.36 (m, 1H), 7.37-7.43 (m, 2H), 7.47-7.52 (m, 2H), 7.57-7.59 (m, 1H).Example 19A Example 17A Further Preparation Method:10589] 200 g (1 mol) of 2-amino-3-benzyloxypyridinewere initially charged in 4 1 of dichloromethane, and at 00 C. a solution of 62 ml (1.2 mol) of bromine in 620 ml of dichioromethane was added over 30 mm. After the addition had ended, the reaction solution was stirred at 00 C. for 60 mm. About 4 1 of saturated aqueous sodium bicarbonate solution were then added to the mixture. The organic phase was removed and concentrated. The residue was purified by silica gel colunm chromatography (petroleum ether/ethyl acetate 6:4) and the product fractions were concentrated. This gave 214 g (77percent of theory) of the title compound.10590] LC-MS (Method 1): R=0.92 mm MS (ESpos): mlz=279 (M+H)j0592] ‘H-NMR (400 MHz, DMSO-d5): ö=5.16 (s, 2H), 5.94-6.00 (m, 2H), 7.26-7.29 (m, 1H), 7.31-7.36 (m, 1H), 7.37-7.43 (m, 2H), 7.47-7.52 (m, 2H), 7.57-7.59 (m, 1H).200 g (1 mol) of 2-amino-3-benzyloxypyridine were initially charged in 4 1 of dichloromethane, and at 0° C. a solution of 62 ml (1.2 mol) of bromine in 620 ml of dichioromethane was added over 30 mm. After the addition had ended, the reaction solution was stirred at 0° C. for 60 mm. About 4 1 of saturated aqueous sodium bicarbonate solution were then added to the mixture. The organic phase was removed and concentrated. The residue was purified by silica gel colunm chromatography (petroleum ether:ethyl acetate 6:4) and the product fractions were concentrated. This gave 214 g (77percent of theory) of the title compound. LC-MS (Method 1): R=0.92 mm, MS (ESpos): mlz=279 (M+H); ‘H-NMR (400 MHz, DMSO-d5): ö=5.16 (s, 2H), 5.94-6.00 (m, 2H), 7.26-7.29 (m, 1H), 7.31-7.36 (m, 1H), 7.37-7.43 (m, 2H), 7.47-7.52 (m, 2H), 7.57-7.59 (m, 1H).200 g (1 mol) of 2-amino-3-benzyloxypyridine were initially charged in 4 1 of dichioromethane, and at 00 C. a solution of 62 ml (1.2 mol) of bromine in 620 ml of dichloromethane was added over 30 mm. After the addition had ended, the reaction solution was stirred at 00 C. for 60 mm. About 4 1 of saturated aqueous sodium bicarbonate solution were then added to the mixture. The organic phase was removed and concentrated. The residue was purified by silica gel colunm chromatography (petroleum ether:ethyl acetate 6:4) and the product fractions were concentrated. This gave 214 g (77percent of theory) of the title compound. LC-MS (Method 1): R=0.92 min. MS (ESpos): mlz=279 (M+H). 1H-NMR (400 Mhz, DMSO-d5): ö=5.16 (s, 2H), 5.94-6.00 (m, 2H), 7.26-7.29 (m, 1H), 7.31-7.36 (m, 1H), 7.37-7.43 (m, 2H), 7.47-7.52 (m, 2H), 7.57-7.59 (m, 1H).200 g (1 mol) of 2-amino-3-benzyloxypyridine were initially charged in 4 1 of dichloromethane, and at 00 C. a solution of 62 ml (1.2 mol) of bromine in 620 ml of dichioromethane was added over 30 mm Afier the addition had ended, the reaction solution was stirred at 00 C. for 60 mm. The mixture was then quenched with about 4 1 of saturated sodium bicarbonate solution. The organic phase was removed and concentrated. The residue was purified by silica gel colunm chromatography (petroleum ether/ethyl acetate=6:4) and the product fractions were concentrated. This gave 214 g (77percent of theory) of the title compound.10534] LC-MS (Method 2): R=0.92 mm10535] MS (ESpos): mlz=279 (M+H)10536] ‘H-NMR (400 MHz, DMSO-d5): ö=5.16 (s, 2H), 5.94-6.00 (m, 2H), 7.26-7.29 (m, 1H), 7.31-7.36 (m, 1H), 7.37-7.43 (m, 2H), 7.47-7.52 (m, 2H), 7.57-7.59 (m, 1H).Sulfuric acid (10percent, 160 mL) was introduced in a three necked flask equipped with mechanical stirrer. 3-Benzyloxypyridi-2-ylamine 12 (8 g, 40 mmol) was added at room temperature under efficient stirring. The reaction mixture was cooled at 0 °C, where a mixture of BrTo a solution of 3-benzyloxy-pyridin-2-ylamine (2.00 g, 10.0 mmol) in DMF (15 mL) was slowly added bromine (0.56 mL, 11 mmol) at 0 1. To a stirred solution of 2-amino-3-benzyloxypyridine (42.0 g, 0.21 mol) in CHStep A: Preparation of 3-(benzyloxy)-5-bromopyridin-2-arnine:; 3-(Benzyloxy)pyridin-2-amine (25.0 g, 124.9 mmol) was added to acetonitrile (300 mL) and cooled to 0

Molecular Weight:279.13
XLogP3:2.7
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:3
Rotatable Bond Count:3
Exact Mass:278.00548
Monoisotopic Mass:278.00548
Topological Polar Surface Area:48.1
Heavy Atom Count:16
Complexity:209
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes