3-(2-aminoethyl)-1,3-dihydroindol-2-one;hydrochloride

Conditions: temp:100.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: A mixture of 4-(((1R,3S)-2,2-dimethyl-3-(1-(tetrahydro-2H-pyran-2-yl)-1H-1,2,4-triazol-3-yl)cyclobutyl)amino)-2-(methylsulfonyl)pyrimidine-5-carbonitrile (140 mg, crude), 3-(2-aminoethyl)indolin-2-one hydrochloride (80 mg, 0.376 mmol) and DIEA (194 mg, 1.50 mmol) in NMP (2.0 mL) was stirred at 100° C. for 1 h. Th reaction was diluted with water and extracted with ethyl acetate. The combined organic layers were dried over anhydrous sodium sulfate and concentrated to give a crude product, which was dissolved in a solution of hydrochloride in MeOH (2N, 5 mL) and stirred at room temperature for 5 h. The reaction was neutralized with ammonia and concentrated. The residue was purified by standard methods to afford the title compound (33.4 mg, 0.075 mmol, 20% yield for two steps). 1H NMR (400 MHz, DMSO-d6) δ (ppm) 13.49 (brs, 1H), 10.24 (s, 1H), 8.52-7.41 (m, 3H), 7.29 (t, J=7.6 Hz, 1H), 7.25-7.07 (m, 2H), 7.01-6.93 (m, 1H), 6.87-6.82 (m, 1H), 4.41-4.29 (m, 1H), 3.59-3.43 (m, 2H), 3.42-3.25 (m, 1H), 3.10-2.96 (m, 1H), 2.81-2.66 (m, 1H), 2.49-2.34 (m, 1H), 2.16-1.94 (m, 2H), 1.49-1.00 (m, 3H), 0.63-0.62 (m, 3H). MS (ESI) m/z 444.2 [M+H]+. extracted with ethyl acetate The combined organic layers were dried over anhydrous sodium sulfate concentrated to give a crude product, which stirred at room temperature for 5 h concentrated The residue was purified by standard methods

Conditions: temp:50.01; pressure:0.00; stir:; See reaction.notes.procedure_details.

Procedure: To a solution of 2-(1H-indol-3-yl)ethanamine (6.00 g, 37.50 mmol) in DMSO (8.0 mL, 112.50 mmol) was added concentrated hydrochloric acid (9.5 mL, 112.50 mmol) slowly. The resulting reaction mixture was stirred at 50° C. in a sealed tube for 16 h. After cooling to room temperature, the reaction mixture was filtered. The resulting cake was stirred in EtOH (15 mL). The mixture was filtered and dried to give the desired title compound as a brown solid (5.00 g, 23.64 mmol, 63% yield). MS (ESI) m/z 177.2 [M+H]+. The resulting reaction mixture After cooling to room temperature the reaction mixture was filtered The resulting cake was stirred in EtOH (15 mL) The mixture was filtered dried

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

Procedure: A mixture of 3-(2-aminoethyl)indolin-2-one hydrochloride (3.20 g, 15.06 mmol), phthalic anhydride (3.34 g, 22.59 mmol) and TEA (4.56 g, 45.18 mmol) in toluene/NMP (20 mL/10 mL). The mixture was heated under reflux for 3 h. The reaction mixture was concentrated and the resulting mixture was washed with saturated aqueous ammonium chloride and brine. The separated organic layer was dried over anhydrous sodium sulfate and filtered. Concentration under vacuum gave the crude product, which was purified by silica gel column chromatography (30% ethyl acetate in petroleum ether) to afford the title compound (2.60 g, 8.50 mmol, 56% yield) as a brown solid. MS (ESI) m/z 307.2 [M+H]+. The mixture was heated under reflux for 3 h The reaction mixture was concentrated the resulting mixture was washed with saturated aqueous ammonium chloride and brine The separated organic layer was dried over anhydrous sodium sulfate filtered Concentration under vacuum gave the crude product, which was purified by silica gel column chromatography (30% ethyl acetate in petroleum ether)