5-Amino-2-chlorobenzonitrile

A mixture of 2-chloro-5-nitrobenzonitrile (10 g, 54.8 mmol) and stannous chloride dihydrate (56 g, 248.6 mmol) in isopropyl alcohol (125 mL) and concentrated hydrochloric acid solution (62.5 mL) was heated to reflux for 1 hour. The mixture was then cooled and neutralized with sodium hydroxide solution (2N). The aqueous layer was extracted with methylene chloride. The combined organic layers were dried over magnesium sulfate and concentrated to afford the title compound (8 g, 96percent). HPLC purity component=100percent at 210-370 nm; RT=7.2 min.; 85/15-5/95 (Ammon. Form. Buff. Ph=3.5/ACN+MeOH) for 10 min., hold 4 min the Xterra.(TM). RP18 instrument, 3.5μ, 150.x.4.6 mm, 1.2 mL/min.Example 72 Conc. HC1 (15.6 ml) was added dropwise to 2-chioro-5- nitrobenzonitrile (3.38 g, 18.5 mmol) and SnC12.2H20 (18.9 g, 83.9 mmol, 4.5 eq.) in isopropanol (35 ml). The mixture was heated at 120° C. for 2 h and then cooled to room temperature and made basic using aq. NaOH. The mixture wasextracted with dichloromethane, dried over Na2SO4 and filtered through silica gel. Concentration under reduced pressure gave 5-amino-2-chlorobenzonitrile (2.58 g, 91percent).55‘H NMR (300 MHz, CDC13): ö=3.90 (br. s, 2H), 6.79 (dm, 1H), 6.91 (m, 1H), 7.22-7.26 (m, 1H) ppm.To a solution of AM-1 -7_N0General procedure: A mixture of N-(2, 6-dichloro-4-nitro-phenyl)-2-methoxy-acetamide (0.290 g, 1.0354 mmol) and tin (II) chloride dihydrate (0.704 g, 3.12 mmol) in ethanol (5 ml_) was refluxed for 3h. TLC (2.5% MeOH in DCM) indicated absence of starting material. The volatiles were removed in vacuo and the residue was suspended in water (15 ml_). The pH was adjusted with 50% aq NaOH to ~ 8 and the suspension was extracted with EtOAc (2 X 30 ml_). The combined EtOAc layer was washed with water, brine and dried over anhyd Na2S04. It was then removed in vacuo and the residue dried further in vacuo to give 0.230 g N-(4-amino-2, 6-dichloro-phenyl)-2-methoxy-acetamide. MS (MH+): 249.a. 5-Amino-2-chlorobenzonitril A solution of 10.0 g (54.8 mmol) 2-chloro-5-nitrobenzonitril in 500 ml ethanol was hydrogenated at 40 psi by using 0.5 g 5% Pd-C as a catalyst. The catalyst was filtered off and the filtrate was evaporated in vacuo. Recrystallization (ethanol-water) gave 3.6 g (43%) 5-amino-2-chlorobenzonitril. M.p. 129-130 C.Acetic anhydride (2.79 ml_, 29.5 mmol),

Used as pharmaceutical intermediate

Molecular Weight:152.58
XLogP3:1.3
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:2
Exact Mass:152.0141259
Monoisotopic Mass:152.0141259
Topological Polar Surface Area:49.8
Heavy Atom Count:10
Complexity:160
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes