3,5-Pyridinediamine

2-Chloro-3, 5-dinitropyridine (4.98 g, 24.46 mmol) was dissolved in ethanol (500 mL) and 5percent palladium on carbon (3.74 g, 0.75 g/g substrate) was added. The mixture was hydrogenated at 25° C. under 50 psi of hydrogen for 18 hrs. The mixture was filtered through celite to remove the catalyst and concentrated under reduced pressure. Purification (silica gel, 20:2:1 CHClThe following Hofmann rearrangement was carried out according to a modified patent procedure.2-Chloro-3, 5-dinitropyridine (4.98 g, 24.46 mmol) was dissolved in ethanol (500 mL) and 5percent palladium on carbon (3.74 g, 0.75 g/g substrate) was added. The mixture was hydrogenated at 25° C. under 50 psi of hydrogen for 18 hrs. The mixture was filtered through celite to remove the catalyst and concentrated under reduced pressure. Purification (silica gel, 20:2:1 CHClThe following Hofmann rearrangement was carried out according to a modified patent procedure.EXAMPLE A-7 3, 5-Pyridinediamine, 2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl 97percent yield from 3, 5-bis-(chlorocarbonyl)-2-(difluoromethyl)-4-(2-methylpropyl)-6-(trifluoromethyl) pyridine product of Step 6 above as a dark oil; used in further steps without purification, since this material is unstable.A mixture of picolinic acid (338 mg, 2.75 mmol), pyridine-3, 5-diamine (300 mg, 2.75 mmol) and EDCI.HC1 (580 mg, 3.02 mmol) in pyridine (5 mL) was heated at 50 C for 2 h. A black solution was formed. LCMS (Rt = 0.329 min; MS Calcd: 214.1; MS Found: 214.9 [M+H]+). The mixture was concentrated and the residue was poured into water (20 mL) and stirred for 2 minutes. The aqueous layer was extracted with ethyl acetate (20 mL x3). The combined organic layer was washed with water (20 mL x2) and brine (20 mL x2), dried over anhydrous Na2S04, filtered and concentrated. The residue was purified by Combi Flash (50% to 100% EtOAc in pentane) to give N-(5-aminopyridin-3-yl)picolinamide (400 mg, yield: 61%) as a light yellow solid. (1416) NMR (400 MHz DMSO-rie) d 5.39 (2H, brs), 7.64 (1H, t, J= 2.3 Hz), 7.67-7.72 (2H, m), A mixture of (lS, 2S)-2-phenylcyclopropane-l-carboxylic acid (360 mg, 2.22 mmol), pyridine-3, 5-diamine (242 mg, 2.22 mmol) and EDCI.HC1 (468 mg, 2.44 mmol) in pyridine (5 mL) was heated at 50 C for 2 h. A black solution was formed. The mixture was concentrated and the residue was poured into water (20 mL) and stirred for 2 minutes. The aqueous layer was extracted with ethyl acetate (20 mL x3). The combined organic layer was washed with water (20 mL x2) and brine (20 mL), dried over anhydrous Na2S04, filtered and concentrated. The residue was purified by Combi Flash (50% to 100% EtOAc in pentane) to give (lS, 2S)-N-(5-aminopyridin-3-yl)-2-phenylcyclopropane-l -carboxamide (390 mg, yield: 64%) as a light yellow solid. (1407) NMR (400 MHz DMSO-rie) d 1.34-1.40 (1H, m), 1.45-1.52 (1H, m), 2.05-2.11 (1H, m), 2.33-2.41 (1H, m), 5.33 (2H, brs), 7.15-7.23 (3H, m), 7.26-7.32 (2H, m), 7.34 (1H, t, .7= 2.1 Hz), 7.62 (1H, d, J= 2.5 Hz), 7.89 (1H, d, J= 2.0 Hz), 10.14 (1H, brs).

Molecular Weight:109.13
XLogP3:-0.5
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:3
Exact Mass:109.063997236
Monoisotopic Mass:109.063997236
Topological Polar Surface Area:64.9
Heavy Atom Count:8
Complexity:66.1
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes