反応 #162064

反応方程式

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

収率 88.0%

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

収率 88.0%

溶媒

dichloromethane

反応条件

後処理

1. 1
   その他reaction
2. 2
   その他the 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
   温度heated at 60° C. in sealed tube for 10 minutes
6. 6
   その他The solution was quenched with aqueous saturated NH4Cl solution (0.5 mL)
7. 7
   その他then evaporated to dryness
8. 8
   workup.DISSOLUTIONThe resulting residue was dissolved in DMSO
9. 9
   その他purified by reverse phase HPLC (ammonium formate buffer)

実験手順

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.

出典