3-amino-1,1,1-trifluoropentan-2-ol

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a stirred solution of (2-fluoro-9-isopropyl-9H-purin-6-yl)-pyridin-3-ylmethyl-amine (300 mg, 1.05 mmol) in n-BuOH/DMSO (5 mL, 4:1) at room temperature under an argon atmosphere was added DIEA (1.4 ml, 10 eq, 8 mmol) followed by 3-amino-1,1,1-trifluoropentan-2-ol (1 g, 6.4 mmol). The flask was fitted with a condenser and the reaction mixture was placed in a preheated oil bath at 140° C. and stirred at this temperature for 72 h. The reaction mixture was allowed to cool to room temperature and the solvent was evaporated in vacuo. The residue was partitioned between EtOAc (50 ml) and water (50 ml), the aqueous phase was extracted with more EtOAc (2×25 ml), and the combined organic phase was washed with brine (50 ml), dried (MgSO4) and evaporated in vacuo. The residue was purified by gradient flash column chromatography on silica gel eluted with CHCl3:MeOH (100:0→95:5), to afford the title compound as a colorless film (42 mg, 9.4%). δH (CDCl3, 500 MHz) 1.04 (3 H, t, J 7.5, CHCH2CH3) 1.56 (6 H, d, J 7.5, CH[CH3]2), 1.8-1.73 (2 H, m, CHCH2CH3), 4.13-4.07 (1 H, m, CHMe2), 4.22-4.2 (1 H, m, CHEt) 4.57-4.55 (1 H, m, CHOHCF3), 4.71 (2 H, s, b, NHCH2Ar), 5.08 (1 H, s, b, NH), 7.2 (1 H, dd, J 5, 10 ArH), 7.51 (1 H, s, ArH), 7.64 (1 H, d, J 10, ArH), 8.46 (1 H, d, J 5, ArH), 8.55 (1 H, s, ArH); δC (CDCl3, 500 MHz) 159.28 (C), 154.72 (C), 149.07 (CH), 148.47 (CH), 135.44 (CH), 134.83 (C), 134.48 (CH), 124.12 (C), 123.44 (CH), 114.62 (C), 73.1 (CH), 55.88 (CH), 46.70 (CH), 41.78 (CH2), 23.68 (CH2) 22.36 (2×CH3), 11.55 (CH3); 19FNMR δ −74.83; m/z 424.2 (M+H) The flask was fitted with a condenser the reaction mixture was placed in a preheated oil bath at 140° C. the solvent was evaporated in vacuo The residue was partitioned between EtOAc (50 ml) and water (50 ml) the aqueous phase was extracted with more EtOAc (2×25 ml) the combined organic phase was washed with brine (50 ml) dried (MgSO4) evaporated in vacuo The residue was purified by gradient flash column chromatography on silica gel eluted with CHCl3:MeOH (100:0→95:5)

Conditions: temp:0.00; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: 1,1,1-trifluoro-3-nitropentan-2-ol (3 g, 16 mmol) was dissolved in methanol (40 ml). Raney Nickel catalyst was added and the reaction vigorously stirred under an atmosphere of hydrogen for 24 h. The catalyst was filtered and the filtrate was concentrated in vacuo to give the amine relatively pure (2.35 g, 94%). δH (CDCl3, 500 MHz) 1.05 (3 H, t, J 5, CHCH2CH3), 1.55-1.45 (1 H, m, CHCHHCH3), 1.8-1.7 (1 H, m, CHCHHCH3), 2.95-2.9 (1 H, m, CHEt), 3.95-3.85 (1 H, m, CHOHCF3); δC (CDCl3, 500 MHz) 124.5 (C), 71.5 (CH), 54.03 (CH), 25.5 (CH2), 11.05 (CH3) the reaction The catalyst was filtered the filtrate was concentrated in vacuo