2-CHLORO-4,5-DIAMINOBENZOTRIFLUORIDE

To a solution of 5-chloro-2-nitro-4-(trifluoromethyl)aniline (2g, 8.3lmmol) in EtOH:H20 (5:1, lOmL) was added SnCl2 (4.73g, 24.9mmol) at rt. The reaction mixture was stirred at 800 C for 3h. The TLC showed reaction to be complete. The reaction mixture was filtered through celite bed and concentrated under reduced pressure to afford 4-chloro-5-(trifluoromethyl)benzene-1, 2-diamine as yellow semi solid. Yield:1.7 g (97percent);1H NMR (400 MHz, DMSO-d6): 6.95 (5, 1H), 6.88 (5, 1H), 4.68-5.08 (bs, 4H), MS (ESI-) for CHNOS m/z 209.15 [M-H].General procedure: A solution of intermediate 6 (1.0 equiv.) and substituted o-phenylenediamine (1.0 equiv.) in 15 mL acetonitrile was stirred at roomtemperature overnight. TLC was used to monitor the progress of the reaction. When the reaction finished, the mixture was addedBOP (1.5 equiv.) and DBU (2.0 equiv.) and was stirred at room temperature. TLC was used to monitor the progressof the reaction. The solutionwas treated with water and ethyl acetate. The organic phases were combined anddried over and evaporated to dryness under reduced pressure. Purification bychromatography using petroleum ether/ethyl acetate 2:1 yielded 7a.Step 1: (1 S, 5R)-2-(tert-butoxycarbonyl)-2-azabicyclo[3.1.0]hexane-1 -carboxylic acid (830 mg; 3.47 mmol) is dissolved in DCM (12 ml) and HATU (1583 mg; 4.16 mmol) is added followed by the addition of DIPEA (1.48 ml; 8.67 mmol). Stirring at rt is continued for 10 min, followed by the addition of 4-chloro-5-(trifluoromethyl)benzene- 1, 2-diamine (877 mg; 4.16 mmol) and stirring is continued at rt for 16 h. The reaction mixture is quenched by the addition of water 20 ml) followed by the separation of the organic phase. The aqueous phase is extracted with DCM (15 ml) and the combined organic phases are washed with brine (20 ml), dried over magnesium sulfate and concentrated under reduced pressure. The residue is purified by preparative HPLC (conditions C) to give 1.069 g; 2.55 mmol) of tert-butyl (1S, 5R)-1-((2-amino-4-chloro-5-(trifluoromethyl)phenyl)carbamoyl)-2- azabicyclo[3.1.0]hexane-2-carboxylate as a slightly brown solid. LC-MS (conditions A): tR = 1.05 min; [M+H]+ = 420.16/422.16 (Cl isotops).D. 3, 4-Diamino-6-chlorobenzotrifluoride To a stirred mixture of 3-amino-6-chloro-4-nitrobenzotrifluoride (300 mg, 1.25 mmol) in ethanol (5 mL) was added SnCl2 ·2H2 O (1.40 g, 6.20 mmol) in one portion. The mixture was refluxed at 80 C. (oil bath, 90 C.) for 1 h and the solution was cooled to room temperature and ice water (20 g) was added. It was adjusted to pH=7 and extracted with ethyl acetate. The extract was dried over Mg2 SO4 and evaporated to give 185 mg (71%) of To a solution of Intermediate II (300 mg, 0.887 mmol) and triethylamine (500 mg, 5 mmol) in DMF (5 mL) was added HATU (370 mg, 0.97 mmol) at 0 C. After the mixture was stirred for 15 min,

Molecular Weight:210.58
XLogP3:2.1
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:5
Exact Mass:210.0171604
Monoisotopic Mass:210.0171604
Topological Polar Surface Area:52
Heavy Atom Count:13
Complexity:185
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes