Diisopropylamine → HCID 12088082, compound

Participants

Reaction Steps

The 4-Chloro-N2-[(1S)-1-(4-fluorophenyl)ethyl]-1,3,5-triazine-2,6-diamine used was prepared from (1S)-1-(4-Fluorophenyl)ethylamine (resolved by the procedure of Takenaka, S. et al. J. Chem. Soc., Perkins Trans. 2 1978, 95-99), cyanuric chloride and ammonium hydroxide according to the procedure outlined in the first two steps of Scheme 3 and by the procedure as described in Examples 14 and 15. A stirred solution of 4-Chloro-N2-[(1S)-1-(4-fluorophenyl)ethyl]-1,3,5-triazine-2,6-diamine (1.15 g, 4.30 mmol), 2-(2-aminoethyl)pyridine (0.58 g, 4.73 mmol), diisopropylamine (20 ml), and THF (10 ml) was heated at reflux for 18 hours and then concentrated under reduced pressure. The yellow residue was taken up in CH2Cl2 and washed with H2O and brine, dried over sodium sulfate, filtered and concentrated under reduced pressure. The residue was chromatographed on silica, eluting with 3% MeOH/CH2Cl2 to afford N2-[(1S)-1-(4-Fluorophenyl)ethyl]-N4-[2-(2-pyridinyl)ethyl]-1,3,5-triazine-2,4,6-triamine (free base) as a pale tan foam (1.10 g, 72%). 1H NMR (CDCl3) δ 8.51 (s, 1H), 7.56 (t, 1H), 7.31 (s, 2H), 7.08 (m, 1H), 6.97 (m, 3H), 5.88-5.44 (b m, 1H), 5.42-5.19 (b m, 1H), 5.15 (m, 1H), 4.95 (b s, 2H), 3.72 (d, 2H), 3.20-2.81 (b m, 2H), 1.47 (d, 3H). HPLC-MS (C-18, MeOH/H2O/TFA linear gradient elution, 5 ml/min, 220 nm): 1 peak at 0.84 minutes; MS (ES+) obs. m/z 353.83. A stirred solution of N2-[(1S)-1-(4-Fluorophenyl)ethyl]-N4-[2-(2-pyridinyl)ethyl]-1,3,5-triazine-2,4,6-triamine was treated with 10 mL of 1 N HCl in Et2O and allowed to stand at ambient temperature for 30 minutes. The mixture was concentrated by rotary evaporation to afford the titled compound as a pale white fine powder. LC/MS (C-18, MeOH/H2OTFA linear gradient elution, 5 ml/min, 220 nm): 1 peak at 0.86 minutes; MS (ES+) obsd m/z=354.26. MP=161° C.

Provenance & Evidence