2,3-Diamino-5-trifluoromethylpyridine

Production Example 59-2 General procedure: Step 1: To a solution of compound 47 (35 mg, 0.097 mmol) in 3% HOAc/DMF (2 mL) wasadded 4, 5-difluorobenzene-1, 2-diamine (28 mg, 0.194 mmol) and potassiumperoxymonosulfate (Oxone, 60 mg, 0.097 mmol). The reaction was stirred at 80C for 16 hr. Thesolution was cooled to ambient temperature and neutralized with K2CO3 (30 mg). The mixturewas patitioned between EtOAc (6 mL) and water (2 mL). The organic phase was isolated andevaporated in vacuum.To a solution of l-(5-(3-bromobenzamido)pyridin-2-yl)cyclobutanecarboxylic acid (100 mg, 0.267 mmol) in pyridine (5 mL) was added 5-(trifluoromethyl)pyridine-2, 3- diamine (48 mg, 0.27 mmol) and EDC (153 mg, 0.800 mmol) at RT. After the addition was complete, the reaction mixture was stirred at 30 °C for 2 h. The reaction was cooled to RT, diluted with water, and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2S04i filtered and concentrated in vacuo to afford the title compound, which was used directly in next step without further purification. MS (EI) m/z 534 [M+H]+.To a stirred solution of 2-(6-bromopyridin-3-yl)-2-methoxyacetic acid (500 mg, 2.03 mmol) in pyridine(5 mL) was added 5 -(trifluoromethyl)pyridine-2, 3 -diamine (396 mg, 2.23 mmol) and EDC (1.17 g, 6.10 mmol) at RT. After the addition was finished, the reaction was stirred at 40 °C for 4 h. The solvent was removed in vacuo. The residue was diluted with water, extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2S04i filtered and concentrated in vacuo to afford a residue, which was purified by prep-TLC (petroleum ether : ethyl acetate =1 : 1) to give the title compound. MS (EI) m/z 405 [M+H]+.To a solution of 3-(4-bromophenyl)oxetane-3-carboxylic acid (550.0 mg, 2.139 mmol) in DCM (15.0 mL) was added HATU (976 mg, 2.57 mmol). The reaction was stirred for 10 min. Then to the reaction mixture were added To a stirred solution of l-(4-(3-cyanobenzamido)phenyl)cyclobutanecarboxylic acid (65 mg, 0.20 mmol) in pyridine (2 mL) was added EDC (97 mg, 0.51 mmol) and 5- (trifluoromethyl)pyridine-2, 3-diamine (30 mg, 0.17 mmol) at RT. After the addition was finished, the mixture was stirred at 40 °C for 16 h. The reaction was diluted with water and extracted with ethyl acetate. The combined organic layers were washed with brine, dried over Na2S04i filtered and concentrated in vacuo to afford a residue, which was purified by reversed phase HPLC, eluting with water (0.1percentTFA)-ACN to give te title compound. MS (EI) m/z 480 [M+H]+.To a vial were added l-(4-(methoxycarbonyl)phenyl)cyclobutanecarboxylic acid (25 mg, 0.11 mmol),

Molecular Weight:177.13
XLogP3:0.7
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:6
Exact Mass:177.05138169
Monoisotopic Mass:177.05138169
Topological Polar Surface Area:64.9
Heavy Atom Count:12
Complexity:159
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes