Pseudoephedrine → n1-[(1r,2s)-2-Hydroxy-1-methyl-2-phenylethyl]-n1-methyl-2-[4-amino-3-(4-{[(2,3-dichlorophenyl)sulfonyl]amino}-3-fluorophenyl)-1h-pyrazolo[3,4-d]pyrimidin-1-yl]acetamide

Participants

Reaction Conditions

Reaction Steps

A solution of (+)-pseudoephedrine (0.037 g, 0.224 mmol) in ethylene glycol dimethyl ether (0.75 mL) was treated with a solution of n-butyllithium (2.5 M in hexanes, 0.060 mL, 0.150 mmol). After 20 min, this solution was transferred via cannula into a solution of ethyl 2-[4-amino-3-(4-{[(2,3-dichlorophenyl)sulfonyl]amino}-3-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]acetate (0.040 g, 0.074 mmol) in N,N-dimethylfornamide (0.75 mL). The resulting solution was stirred at 50° C. for 15 h. It was then cooled to ambient temperature and partitioned between methanol/dichloromethane (1:9, 50 mL), and water (15 mL). The organic layer was separated, dried over magnesium sulfate, filtered, and concentrated under reduced pressure. Purification by preparative HPLC (25 to 100% acetonitrile in 0.1 M aqueous ammonium acetate over 20 min at 21 mL/min using an 8μ Hypersil HS C18, 250×21 mm column, Rt 11.88-12.65 min) afforded N1-[(1R,2S)-2-hydroxy-1-methyl-2-phenylethyl]-N1-methyl-2-[4-amino-3-(4-{[(2,3-dichlorophenyl)sulfonyl]amino}-3-fluorophenyl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl]acetamide as an off-white solid (0.010 g, 0.015 mmol): RP-HPLC (25 to 100% acetonitrile in 0.1 M aqueous ammonium acetate over 10 min at 1 mL/min using a Hypersi1HS C18, 250×4.6 mm column) Rt 9.63 min; MS: (MH)+ 658.

Provenance & Evidence