تفاعل #519556

ord-57433a48d8b243a88c332ed73ae5f32b

ظروف التفاعل

درجة الحرارة
50°CELSIUS
الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    درجة الحرارةIt was then cooled to ambient temperature
  2. 2
    أخرىpartitioned between methanol/dichloromethane (1:9, 50 mL), and water (15 mL)
  3. 3
    أخرىThe organic layer was separated
  4. 4
    تجفيفdried over magnesium sulfate
  5. 5
    ترشيحfiltered
  6. 6
    تركيزconcentrated under reduced pressure
  7. 7
    أخرىPurification by preparative HPLC (25 to 100% acetonitrile in 0.1 M aqueous ammonium acetate over 20 min at 21 mL/min

الإجراء التجريبي

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.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US06660744B1uspto-grants-2003_12