Pyridine, 5-bromo-2-(chloromethyl)- (9CI)

Part B: Compound 413A (500 mg, 2.7 mmol) was dissolved in methylene chloride (5 mL) and cooled in an ice bath. Thionyl chloride (480 mg, 4.05 mmol) was added dropwise and stirred at room temperature for 3 hours. The reaction was quenched with saturated sodium bicarbonate. The organic layer was dried over sodium sulfate and concentrated to provide the desired product (510 mg, 92percent).Step 1 To the stirred solution of (5-Bromo-pyridin-2-yl)-Methanol (5gm, 26.59mmol, 1 eq) in DCM (50mL) at 0°C is added Thionyl chloride (3ml_) drop wise at RT then stirred at RT for 4h. After completion, the reaction mixture quenched with saturated sodium bicarbonate solution and extracted with DCM (3X100ml_). The combined organic layer dried over sodium sulphate and evaporated under reduced pressure. The crude is purified by column chromatography using silica 100-200 mesh using 10percent EtOAc: Hexane as eluent to afford title compound (4g) as brown colored liquid. 1 NMR (400 MHz, DMSO) δ: 4.77 (s, 2H), 7.54 (d, J = 8.64Hz, 1 H), 8.09-8.12 (dd, J1 = 2.4Hz, J2 = 8.32Hz, 1 H), 8.70 (d, J = 5.96Hz, 1 H).Part B: Compound 413A (500 mg, 2.7 mmol) was dissolved in methylene chloride (5 mL) and cooled in an ice bath. Thionyl chloride (480 mg, 4.05 mmol) was added dropwise and stirred at room temperature for 3 hours. The reaction was quenched with saturated sodium bicarbonate. The organic layer was dried over sodium sulfate and concentrated to provide the desired product (510 mg, 92%).A slurry of 36 (10.0 g, 33.1mmol) in TBME (100 ml) was treated with 20% potassium, carbonate (20 ml) solution and stirred at room temperature for 1 h. The layers were separated and the organic layer was washed with water. The TBME and water were removed by atmospheric distillation and azeotropic distillation with acetonitrile (100 ml) and further concentrated under vacuum to a volume of 40 ml. A Karl Fischer was performed to confirm the removal of water (KF ' 0.2). To the acetonitrile concentrate was added dropwise thionyl chloride (3.2 ml, 43.7 mmol) while keeping the temperature below 45 0C. The reaction mixture was then heated at 45 C for 2 h at which time an HPLC assay indicated complete reaction. The reaction mixture was cooled to 25 0C and quenched with water (20 ml) while keeping the temperature below 40 0C. The reaction mixture was slowly poured into a mixture of 20% sodium carbonate (40 ml) and toluene (100 ml), stirred for 10 min and the layers were partitioned. The toluene extract was concentrated under reduced pressure to a volume of about 20 ml. A KF was performed to confirm the removal of water (KF ' 0.2).Example 1A; Preparation of [(5-Bromo-Pyridin-2-ylMethyl)-Phosphonic Acid Diethyl Ester] Hydrochloride; Into a solution of 5-bromo-2-hydroxymethyl-pyridine (BHMP, 50.0 g, 266 mmol) in toluene (100 mL) and MeCN (150 mL) was added thionyl chloride (35.0 mL, 57.1 g, 479 mmol). This reaction mixture was stirred at 45 C. for 4 hours. Toluene (250 mL) was added to the reaction mixture and the reaction mixture was cooled to 0 C. The reaction was quenched with 20% potassium carbonate solution (450 ml), keeping the temperature below 30 C. The reaction mixture was stirred for 10 min and the layers were partitioned. The organic layer was washed once with water (100 mL) and the organic layer was concentrated under reduced pressure to a volume of about 200 mL. The concentrated crude solution was transferred to a distillation apparatus. At room temperature, triethyl phosphite (200 mL, 1144 mmol) was added to the crude concentrated solution and the reaction mixture was heated to 145 C. until reaction was completed. Distillate driven off of the reaction mixture during the heating period was collected (200 mL). After 12 hours of heating the reaction mixture was cooled to 0 C. A solution of 5-6N HCl in isopropanol (150 mL) was slowly added to the cooled reaction mixture over a period of 1 hour, keeping the internal temperature below 5 C. Heptanes (350 mL) were then added to the mixture over 1 hours and the resultant slurry was stirred for another hour. The solid product was collected by vacuum filtration, washed with 10% IPA/heptanes and dried under vacuum at room temperature to provide 81 g of product (89%). Mp. 118-120 C. 1H NMR (400 MHz, CDCl3) delta 1.29 (t, J=7.05 Hz, 6H), 3.88 (d, J=22.3 Hz, 2H), 4.19 (m, 4H), 7.88 (dd, J=8.57 Hz, 1H), 8.34 (dd, J=8.55, 2.18 Hz, 1H), 8.71 (s, 1H).NaH (0.525 g, 13.1 mmol, 60% in mineral oil) was added to a solution of alcohol 41 (1.872, 10.1 mmol) and Step 1 Preparation of To the stirred solution of (5-Bromo-pyridin-2-yl)-Methanol (5gm, 26.59mmol, 1 eq) in DCM (50mL) at 0C is added Thionyl chloride (3ml_) drop wise at RT then stirred at RT for 4h. After completion, the reaction mixture quenched with saturated sodium bicarbonate solution and extracted with DCM (3X100ml_). The combined organic layer dried over sodium sulphate and evaporated under reduced pressure. The crude is purified by column chromatography using silica 100-200 mesh using 10% EtOAc: Hexane as eluent to afford title compound (4g) as brown colored liquid. 1 NMR (400 MHz, DMSO) delta: 4.77 (s, 2H), 7.54 (d, J = 8.64Hz, 1 H), 8.09-8.12 (dd, J1 = 2.4Hz, J2 = 8.32Hz, 1 H), 8.70 (d, J = 5.96Hz, 1 H).tert-Butyl (5S)-2-[(5-bromopyridin-2-yl)methyl]-3-oxo-2, 3, 5, 6, 7, 8-hexahydro[1, 2, 4]triazolo[4, 3-a]pyridine-5-carboxylate tert-Butyl (5S)-3-oxo-2, 3, 5, 6, 7, 8-hexahydro[1, 2, 4]triazolo[4, 3-a]pyridine-5-carboxylate (309 mg, 1.29 mmol) was initially charged in dichloromethane (7.3 ml). Caesium carbonate (1.05 g, 3.23 mmol) and 1 ml of a 30 % aqueous sodium hydroxide solution, tetrabutylammonium bromide (60 mg, 0.18 mmol) and then In -60 C, Ar under protection, NaH (60%, 130 mg, 5.4mmol) adding (S)-2 - nitro - 6, 7 - dihydro - 5H - imidazole [2, 1 - the b] [1, 3] oxazine -6 - alcohol (500 mg, 2 . 7mmol) and 5 - bromo -2 - fluoro pyrimidine (570 mg, 3 . 2mmol) of DMF (5 ml) solution. The solution stirring at room temperature 3 hours, inverted water (50 ml) in. Filtering, solid dissolved in EtOAc, salt water washing, drying (Na2SO4). Evaporate the solvent to obtain the white solid product.Intermediate 20. Reference to the method of Intermediate 1 synthesisTo a solution of (S)-4-methyl-2-((2-((2-(trimethylsilyl)ethoxy)methyl)-2H- tetrazol-5-yl)methyl)pentanoic acid (800 mg, 2.44 mmol) in THF (30 ml) was added LDA (8.7 ml, 6.1 mmol). The solution turned bright yellow half way through the base addition. The mixture was allowed to stir at -78C for 45 minutes before To the stirred solution of

Molecular Weight:206.47
XLogP3:2
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:204.92939
Monoisotopic Mass:204.92939
Topological Polar Surface Area:12.9
Heavy Atom Count:9
Complexity:89.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes