1-(3-Bromophenyl)cyclopropanamine

To a solution of 3-bromobenzonitrile (10 g, 55 mmol) and Ti(O-iPr)4 (17.2 g, 18 mL, 60.4 mmol) in THF (100 mL) was added dropwise EtMgBr (40.3 mL, 121 mmol, 3M in THF) at -78 00. The reaction was slowly warmed to room temperature for 1 h then BF3'OEt2 (13.9 mL, 110 mmol) was added. Stirring was continued for 16 h then the reaction was quenched with 1 N HCI (150 mL). The mixture was neutralized with 10% NaOH (200 mL) and extracted with EtOAc (300 mL). The organic solution was used for next step directly.General procedure: 3-(trifluoromethyl)benzene-l-sulfonyl chloride (0.66 mL, 4.1 mmol) was added into a mixture of (3-bromophenyl)methanamine hydrochloride (1.0 g, 4.5 mmol) and DIEA(1.6 mL, 9.0 mmol) in DCM (20 mL). The reaction was stirred at room temperature for approximately 3 hours and washed with IN HC1 (IX) and brine (2X). The organic layer was dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was purified by silica gel chromatography (0 - 30% EtOAc/Hexanes) to afford the title compound (1.5 g, 96%). l NMR (CDC13) delta 8.05 (s, IH), 8.00 (d, IH), 7.82 (d, IH), 7.63 (t, IH), 7.35 (m, IH), 7.27 (s, IH), 7.12 (d, 2H), 5.25 (t, IH), 4.18 (d, 2H). To a solution of To a solution of l-(4-fluoro-phenyl)-lH-pyrazolo[3, 4-c]pyridine-4-carboxylic acid (0.500 g, 1.94 mmol), l-(3-bromophenyl)cyclopropanamine (453 mg, 2.14 mmol) and N, N-diisopropylethylamine (1.73 mL, 9.72 mmol) in DMF (18 mL) is added TBTU (0.780 g, 2.43 mmol). After 2 hours, the mixture is concentrated in vacuo, dissolved in ethyl acetate (200 mL), and washed with 2Nu sodium hydroxide (3 x 100 mL), saturated aqueous ammonium chloride (2 x 100 mL), saturated aqueous sodium bicarbonate (100 mL), brine (100 mL). The organic layer is dried over MgS04, filtered through a pad of silica gel eluting with ethyl acetate (3 x 100 mL), and concentrated in vacuo. The residue is purified by silica gel chromatography eluting with a gradient of 50-70% ethyl acetate in heptane to give a solid that is triturated with methylene chloride to afford the title compound as a solid.Step 1: tert-butyl 4-(4-(1-(3-bromophenyl)cyclopropylamino)-6-(2, 2, 2-trifluoroethoxy)-1, 3, 5-triazin-2-ylamino)benzoate. To a solution of tert-butyl 4-(4-chloro-6-(2, 2, 2-trifluoroethoxy)-1, 3, 5-triazin-2-ylamino)benzoate (1156 mg, 2 mmol) in THF (10 mL) was added Step 1: tert-butyl 4-(4-(l-(3-bromophenyl)cyclopropylamino)-6-(2, 2, 2- trifluoroethoxy)-l, 3, 5-triazin-2-ylamino)benzoate. To a solution of tert-butyl 4-(4- chloro-6-(2, 2, 2-trifluoroethoxy)-l, 3, 5-triazin-2-ylamino)benzoate (1156 mg, 2 mmol) in THF (10 mL) was added l-(3-bromophenyl)cyclopropanamine (424 mg, 2.000 mmol) and Hunig'sBase (1.747 mL, 10.00 mmol). The resulting mixture was stirred for 16 h. After concentration, the residue was purified by Biotage eluting with 20% ethyl acetate in hexane to give 400 mg (35%) of the desired product as a solid.LC ConditionSolvent A 10 % methanol: 90% Water : 0.1% TFASolvent B 90 % methanol: 10% Water : 0.1% TFAStart % B 0Final % B 100Gradient/Stop Time 3 min / 4 minFlow Rate 1 mL/minWavelength 220Solvent Pair methanol: Water: TFAColumn PHENOMENEX-LU A 2.0 X 30mm 3um

Molecular Weight:212.09
XLogP3:1.8
Hydrogen Bond Donor Count:1
Hydrogen Bond Acceptor Count:1
Rotatable Bond Count:1
Exact Mass:210.99966
Monoisotopic Mass:210.99966
Topological Polar Surface Area:26
Heavy Atom Count:11
Complexity:154
Covalently-Bonded Unit Count:1
Compound Is Canonicalized:Yes