반응 #162064

반응 방정식

cyclopentylmethanesulfonyl chloride

Morpholine

N-(azetidin-3-yl)-2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-amine hydrochloride

6c

N-(azetidin-3-yl)-2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-amine hydrochloride

iPr2NEt

→

desired product

수율 88.0%

2-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-N-(1-(cyclopentyl-methylsulfonyl)azetidin-3-yl)-5-fluoropyrimidin-4-amine

수율 88.0%

용매

dichloromethane

반응 조건

후처리

1. 1
   기타reaction
2. 2
   기타the 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
   온도heated at 60° C. in sealed tube for 10 minutes
6. 6
   기타The solution was quenched with aqueous saturated NH4Cl solution (0.5 mL)
7. 7
   기타then evaporated to dryness
8. 8
   workup.DISSOLUTIONThe resulting residue was dissolved in DMSO
9. 9
   기타purified by reverse phase HPLC (ammonium formate buffer)

실험 절차

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.

출처