6-Chloro-3-pyridineacetonitrile

(1 R)-1-(6-amιno-Pyrιdιn-3-yl-acetyl amιno)-2-(2-hvdroxy-3-carboxyphenyl)ethyl-1- boronic acid formateStep 1. Synthesis of (6-chloropyridin-3-yl) acetonitrite. To a solution of 2-chloro-5-(chloromethyl)pyrιdιne (25 g, 0 154 mol) in ethanol (40 mL) stirring at 0 °C was added a solution of sodium cyanide (8 17 g 0 167 mol) in water (18 mL) The reaction mixture was refluxed for 2 hours then stirred at ambient temperature for a further 18 hours The solvent was evaporated in vacuo and the residue extracted from water into DCM (500 mL), washed with brine dned over sodium sulfate, filtered and evaporated in vacuo The crude material was purified by column chromatography over silica gel eluting with 70/30 DCM/hexanes to afford 20 g (85percent) of product as brown oil which solidified on standing ESI-MS m/z 153 (MH)To a stirred solution of 2-chloro-5-(chloromethyl)pyridine (1 g, 6.17 mmol, 1.0 equiv.) in ethanol (10 ml_) was added the solution of NaCN (325 mg, 6.79 mmol, 1.1eq) in HTo a stirred solution of 2-chloro-5-(chloromethyl)pyridine (1 g, 6.17 mmol, 1.0 eq) in ethanol (10 mL) was added the solution of NaCN (325 mg, 6.79 mmol, 1.1 eq) in water (10 mL) dropwise at 0 °C and then stirred for 3 h at 100 °C. The reaction mixture was diluted with water (50 mL), extracted with ethyl acetate (2 x 70 mL) washed with brine (20 mL). The organic layer was dried over anhydrous sodium sulphate and evaporated under vacuum. The crude was purified by using silica gel chromatography (100-200 mesh) using ethyl acetate /petrol ether (3:7) to get 2-(6-chloropyridin-3-yl)acetonitrile (400 mg, 63 percent) as a yellow solid.Step 1: Step 1 16.2 g 2-chloropyridine benzyl chlorine, 5.1 g of sodium cyanide are added to a 250 ml four-mouthed flask. Add 150 ml ethanol, 11 g sodium carbonate. Heat to reflux. Reflux reaction for 4 hours. After the reaction, prolapsed ethanol, add 100 g water and stirred, filtered to obtain 21 g 2-chloropyridine acetonitrile.To a solution of 2-chloro-5-(chlofomethyl)pyridine (75g, 0.46mol) in ethanol (120ml) stirring at O1.17.a To a solution of 2-chloro-5-(chloromethyl)pyridine (5.0 g, 0.031 mol) in ethanol (38 mL) and water (19 mL) was added potassium cyanide (2.41 g, 0.0370 mol) at RT under nitrogen atmosphere. A solution of 5.2 g (32 MMOL) of 2-chloro-5-chloromethylpyridine dissolved in 40 mL of ethanol was treated with 20 mL of water and 2.4 g (37 MMOL) of potassium cyanide. The mixture was stirred and heated at 50 °C for 20 hours. The dark mixture was then partitioned between DICHLOROMETHANE and water and the organic layer was washed with brine and dried over sodium sulfate. The solvent was removed under reduced pressure to yield 4.54 g (92percent) of Preparatory Compound E, (6-chloro-3- pyridinyl) acetonitrile, as a dark brown liquid :'H NMR (CDCI3) 8 8.38 (d, J = 3.0 Hz, 1H), 7.71 (dd, J = 3.0 and 7.6 Hz, 1H), 7.42 (d, J = 7.6 Hz, 1H), 3.80 (s, 2H) ppm. GCMS: (EI) m/z 152 (M+).

Molecular Weight:152.58
XLogP3:1.5
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:152.0141259
Monoisotopic Mass:152.0141259
Topological Polar Surface Area:36.7
Heavy Atom Count:10
Complexity:149
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes