4-(4-AMINOPHENYL)-PIPERIDINE

NT1-OO1 (400 mg, 1.942 mmol) in MeOH (30mL) was combined with a palladium catalyst (144 mg) under argon. The argon was removed and H2 gas was introduced into the system. After 3.5 hours at room temperature, the palladiumcatalyst was filtered, the solvent removed under reduced pressure. The residue was purified bytrituration with DCM to afford 4-(piperidin-4-yl)aniline (NT1-004) as a white solid (340 mg, 99percent). HPLC 95.0percent [R = 6.74 mm, 30percent CH3OH in 0.1percent TFA water 20 min]. Substrates NT1-008 (100 mg, 0.403 mmol) and NT1-004 (71 mg, 0.403 mmol) were mixed in a microwave tube with EtOH (1.5 mL). Then0.1N HC1 (1 mL) was added to the tube. The vessel was sealed and heated to 150 C for 40 minutes. The solvent was removed under reduced pressure, the residue washed with DCM, and filtered to afford (R)-5 -chloro-N2-(4-(piperidin-4-yl)phenyl)-1V4-((tetrahydrofuran-2- yl)methyl)pyrimidine-2, 4-diamine (NT1-010) as a white solid (87 mg, 56%), mp 160 C (dec.). HPLC 95.3% [R = 7.55 mm, 30% CH3OH in 0.1% TFA water 20 mm]. 'H NMR (400 MHz, Methanol-d4) oe 7.94 (s, 1H), 7.48 (d, J= 8.2 Hz, 2H), 7.36 (d, J 8.4 Hz, 2H), 4.16 (p, J 6.2Hz, 1H), 3.86-3.67 (m, 2H), 3.64 - 3.44 (m, 4H), 3.22-3.09 (m, 2H), 3.02-2.90 (m, 1H), 2.14 - 1.84(m, 8H), 1.69-1.58(m, 1H). '3CNMR(101 MHz, Methanol-d4)oe 159.18, 151.36, 141.70, 139.82, 135.13, 128.13, 127.11, 122.75, 105.10, 76.76, 67.64, 45.27, 44.16, 39.16, 29.68, 28.57, 25.03. LC-MS (ESI+) m/z 388.19139 (M+H) HRMS (ESI+) m/z calculated for C20H26ClN5O(M+H)388.1899, found, 388.1913.A mixture of YL7-1 02 (0.062 g, 0.161 mmol) and NT1-004 (0.028 g, 0.161 mmol) in EtOH (1 mL) and 0.1 M aq. HC1 (1 mL) was heated with microwave reactor at 150 C for 40 mm. The solvent was removed and theresulting residue was slurried with DCM, filtered and dried under high vacuum to afford theentitle compound as a solid (0.032 mg, 36%)); HPLC 89.4% (R = 10.37 mm, 45% CH3OH in0.1% TFA water, 20 mm); 'H NMR (400 MHz, DMSO-d6): oe 8.60 (d, J = 4.0 Hz, 1H), 7.55 (d, J= 7.6 Hz, 2H), 7.40 (s, 1H), 7.39 (d, J= 2.8 Hz, 2H), 7.25-7.19 (m, 1H), 4.19-4.10 (m, 1H), 3.93-3.80 (m, 1H), 3.75-3.60 (m, 3H), 3.53-3.50 (d, J = 12.0 Hz, 2H), 3.16 (t, J = 10.4 Hz, 2H), 3.00-2.93 (t, J = 12.0 Hz, 1H), 2.11-1.89 (m, 6H), 1.67-1.60 (m, 1H). LC-MS (ESI+) m/z 525.2;(M+H) HRMS (ESI+) m/z calculated for C27H3, C1FN6O2 (M+H) 525.2176, found 525.2175.

Molecular Weight:176.26
XLogP3:1.4
Hydrogen Bond Donor Count:2
Hydrogen Bond Acceptor Count:2
Rotatable Bond Count:1
Exact Mass:176.131348519
Monoisotopic Mass:176.131348519
Topological Polar Surface Area:38
Heavy Atom Count:13
Complexity:144
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes