2-Bromo-5-chloro-4-methylbenzenamine

A solution of 4-acetamido-5-bromo-2-chlorotoluene (64 g, 0.245 mol) in glacial acetic acid (48 ml) and concentrated hydrochloric acid (96 ml) was heated at 118 C. for 24 h. The reaction mixture was allowed to cool to room temperature, diluted with water (200 ml), cooled in an ice-bath and the pH was. adjusted to 5 with a aqueous solution of NaOH (50percent w/v). The precipitate was collected by filtration washed with water, and dried in vacuo over P2O5 to afford a white solid (50.7 g, 94percent), mp 90 CExample 41: (5-Chloro-2-((E)-3-13-(4-fl uorobenzvl)-3, 8-diazabicvdo13 .2. I loct-8-vll-3- oxopropenyl} -4-methylphenyl)-urea; a) 2-Bromo-5-chloro-4-methylphenylamine; 3-Chloro-4-methylphenylamine (20.0 g; 0.141 mmol) is dissolved in CH2CI2 (200 ml) and combined within 5 min. with a solution of NBS (25.1 g; 0.141 mmol) in CH2CI2 (800 ml). The reaction mixture is stirred for 5 min at room temp. , evaporated to a volume of -200 ml and diluted with hexanes (1000 ml). The resulting precipitate is filtered off, the filtrate evaporated to dryness and purified via chromatography (Si02, hexanes / TBME 10: 1) to render the title compound as yellowish crystals (12.3 g; 40 percent). A second batch of title compound is obtained by re-chromatography of mixed fractions (7.5 g; 24 percent). 1H-NMR (400MHz; DMSO-d6), No. (ppm) : 2.13 (s, 3H) ; 5.32 (s, 2H, NH2) ; 6.81 (s, 1 H); 7.31 (s, 1 H). MS (m/z) ES+: 221 (100, M+) ; 219 (80) ; 184 (35 ); 140 (100) ; 104 (50) ; 77 (65) ; 52 (58) ; 51 (60).[00148] To a solution of 3-chloro-4-methylaniline (10.0 g, 70.6 mmol) in diethyl ether/acetic acid (v/v 1/1, 350 ml) cooled in an ice-bath was dropwise added bromine (4 ml) over a 35 min period under an argon atmosphere while the temperature of the reaction mixture was kept below 5 C. Stirring was continued for 10 min after the addition of bromine; then the yellow reaction mixture was partitioned between dichloromethane (250 ml) and dilute brine (200 ml). The organic layer was washed with more dilute brine (200 ml), dried (Na2SO4), and concentrated in vacuo to an oily residue. This was redissolved in dichloromethane (200 ml) and the solution was washed with saturated aqueous sodium bicarbonate (3200 ml; caution: gas is evolved), dried (Na2SO4) and concentrated in vacuo to leave a brown wet solid. Purification by column chromatography on gradient elution with dichloromethane in hexanes (25 to 30percent) gave in order of elution: [00149] a. 5-chloro-2, 6-dibromo-4-methylaniline as a white solid (4.63 g) mp 77-78 C. [00150] b. the desired product, 2-bromo-5-chloro-4-methylaniline (5.32 g, 34percent), mp 90 C., 1H-NMR (CDCl3) 2.23 (s, 3H, 4-CH3), 3.99 (br s, 2H, NH2), 6.78 (s, 1H, 6-H), 7.26 (s, 1H, 3-H). MS (FAB, m/z) 219, 221, 223 [(M+H)+, BrCl isotopic pattern]. Elemental Analysis: Found: C, 38.04; H, 3.20; N, 6.35; Cl, 16.04; Br, 36.28. C7H7BrClN requires: C, 38.13; H, 3.20; N, 6.35; Cl, 16.08; Br, 36.24 [00151] c. 2-bromo-3-chloro-4-methylaniline as a white solid (1.22 g) mp 48-56 C.

Molecular Weight:220.49
XLogP3:2.9
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Exact Mass:218.94504
Monoisotopic Mass:218.94504
Topological Polar Surface Area:26
Heavy Atom Count:10
Complexity:120
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes