تفاعل #162064

ord-c2b29f0fc7b041fe86c0a451d685ed86

المذيبات

ظروف التفاعل

الظروف التفصيلية
See reaction.notes.procedure_details.

المعالجة

  1. 1
    أخرىreaction
  2. 2
    أخرىthe solution evaporated to dryness
  3. 3
    workup.DISSOLUTIONThe resulting residue was dissolved in methanol (2 mL)
  4. 4
    workup.ADDITIONthen treated with 25% sodium methoxide/methanol (0.5 mL)
  5. 5
    درجة الحرارةheated at 60° C. in sealed tube for 10 minutes
  6. 6
    أخرىThe solution was quenched with aqueous saturated NH4Cl solution (0.5 mL)
  7. 7
    أخرىthen evaporated to dryness
  8. 8
    workup.DISSOLUTIONThe resulting residue was dissolved in DMSO
  9. 9
    أخرىpurified by reverse phase HPLC (ammonium formate buffer)

الإجراء التجريبي

To a stirred solution of N-(azetidin-3-yl)-2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-amine hydrochloride, 6c, (0.03 g, 0.06 mmol) in dichloromethane (1 mL) was added iPr2NEt (0.33 μL, 1.90 mmol) followed by cyclopentylmethanesulfonyl chloride (0.01 g, 0.06 mmol). The resulting mixture was stirred 30 minutes at room temperature at which time LCMS showed complete reaction. Morpholine (0.20 mL) was added and the solution evaporated to dryness. The resulting residue was dissolved in methanol (2 mL) then treated with 25% sodium methoxide/methanol (0.5 mL) and heated at 60° C. in sealed tube for 10 minutes. The solution was quenched with aqueous saturated NH4Cl solution (0.5 mL) then evaporated to dryness. The resulting residue was dissolved in DMSO and purified by reverse phase HPLC (ammonium formate buffer) to afford 27.4 mg (88% yield) of the desired product, 469, as a solid. LCMS RT=3.1 min, ES+465.

المصدر

DOI: 10.6084/m9.figshare.5104873.v1براءة الاختراع: US08829007B2uspto-grants-2014_09