Hydrochloric Acid → 4-(5-(3-(5H-pyrrolo[3,2-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile

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Reaction Steps

A mixture of 4-(5-amino-6-methylisoquinolin-1-ylamino)benzonitrile (0.150 g, 0.55 mmol) and 4-(2-fluoropyridin-3-yl)-5H-pyrrolo[3,2-d]pyrimidine (0.13 g, 0.60 mmol) in anhydrous THF (10 mL) was stirred at RT and treated dropwise with lithium bis(trimethylsilyl)amide (1.0 M solution in THF; 1.7 mL, 1.7 mmol) to give a dark suspension. After 1 h stirring, the mixture was treated with 1 N aq HCl (10 mL) and stirred at RT for 10 min. The reaction mixture was added to satd NaHCO3 (70 mL) and extracted with 3:1 CHCl3IPA (3×70 mL). The combined organic layers were washed with satd NaCl (50 mL), dried over Na2SO4, filtered, and concentrated in vacuo. The crude product was adsorbed onto a plug of silica gel and chromatographed through a Redi-Sep® pre-packed silica gel column (40 g), eluting with a gradient of 70% to 90% EtOAc in CH2Cl2 to provide 50 mg. The crude product was purified by reverse-phase preparative HPLC using a Phenomenex Gemini column, 10 micron, C18, 110 Å, 150×30 mm, 0.1% TFA in CH3CN/H2O, gradient 10% to 100% over 13 min. Fractions containing product were combined, concentrated in vacuo, and lyophilized to give 4-(5-(3-(5H-pyrrolo[3,2-d]pyrimidin-4-yl)pyridin-2-ylamino)-6-methylisoquinolin-1-ylamino)benzonitrile as a bright yellow solid. MS (ESI, pos. ion) m/z: 469.2 [M+H]+

Provenance & Evidence