Diisopropylethylamine → [2-({3-Methyl-5-[2-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-1,3-thiazol-5-yl]phenyl}amino)-pyrimidin-4-yl](piperazin-1-yl)methanone

Participants

Reaction Steps

To 2-({3-methyl-5-[2-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-1,3-thiazol-5-yl]phenyl}amino)-pyrimidine-4-carboxylic acid (Example 68, 68.9 mg, 0.162 mmol) in a scintillation vial was added DMF (812 μL), tert-butyl piperazine-1-carboxylate (33.4 mg, 0.179 mmol), DIPEA (85 μL, 0.487 mmol) and BOP (108 mg, 0.244 mmol). The reaction was stirred at room temperature for 1 hour before being diluted with water and dichloromethane. The organic was dried over sodium sulfate, filtered and concentrated to dryness. The resultant residue was purified by normal phase chromatography (10% MeOH in DCM: hexanes, 10-100%, linear gradient). Boc deprotection was carried out on the isolated material with 1:1 TFA:dichloromethane (1 mL) at room temperature. Upon completion the reaction was concentrated to dryness and was directly purified by reverse phase chromatography (10-80% MeCN in water, linear gradient) to yield [2-({3-methyl-5-[2-(1,1,1-trifluoro-2-hydroxypropan-2-yl)-1,3-thiazol-5-yl]phenyl}amino)-pyrimidin-4-yl](piperazin-1-yl)methanone as a TEA salt. MS ESI: [M+H]+ m/z 493.1. 1H NMR (500 MHz, DMSO-d6) δ 9.91 (s, 1H), 8.87 (s, 2H), 8.67 (d, J=4.8, 1H), 8.08 (s, 1H), 7.83 (s, 1H), 7.57 (s, 1H), 7.16 (s, 1H), 7.00 (s, 1H), 3.82 (s, 2H), 3.67 (s, 2H), 3.21 (s, 2H), 3.08 (s, 2H), 233 (s, 3H), 1.76 (s, 3H). rhSYK activity=+++

Provenance & Evidence