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

HRID 526893노트

반응식

HRID 526893 반응식
Cl.[NH:2]1[CH2:5][CH:4]([NH:6][C:7]2[C:12]([F:13])=[CH:11][N:10]=[C:9]([C:14]3[C:22]4[C:17](=[N:18][CH:19]=[C:20]([Cl:23])[CH:21]=4)[N:16](S(C4C=CC(C)=CC=4)(=O)=O)[CH:15]=3)[N:8]=2)[CH2:3]1.CCN(C(C)C)C(C)C.[CH:43]1([CH2:48][S:49](Cl)(=[O:51])=[O:50])[CH2:47][CH2:46][CH2:45][CH2:44]1.N1CCOCC1>ClCCl>[Cl:23][C:20]1[CH:21]=[C:22]2[C:14]([C:9]3[N:8]=[C:7]([NH:6][CH:4]4[CH2:5][N:2]([S:49]([CH2:48][CH:43]5[CH2:47][CH2:46][CH2:45][CH2:44]5)(=[O:51])=[O:50])[CH2:3]4)[C:12]([F:13])=[CH:11][N:10]=3)=[CH:15][NH:16][C:17]2=[N:18][CH:19]=1

참가 물질

6

반응물 4

HCID 8083MorpholineHCID 81531DiisopropylethylamineHCID 2735404Cyclopentylmethanesulfonyl ChlorideHCID 67284924N-(azetidin-3-yl)-2-(5-chloro-1-tosyl-1H-pyrrolo[2,3-b]pyridin-3-yl)-5-fluoropyrimidin-4-amine hydrochloride2회

생성물 1

HCID 680079372-(5-chloro-1H-pyrrolo[2,3-b]pyridin-3-yl)-N-(1-(cyclopentyl-methylsulfonyl)azetidin-3-yl)-5-fluoropyrimidin-4-amine수율 88%

시약·촉매·용매 1

HCID 6344Dichloromethane용매

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.

후처리

  1. customreaction
  2. customthe solution evaporated to dryness
  3. dissolutionThe resulting residue was dissolved in methanol (2 mL)
  4. additionthen treated with 25% sodium methoxide/methanol (0.5 mL)
  5. temperatureheated at 60° C. in sealed tube for 10 minutes
  6. customThe solution was quenched with aqueous saturated NH4Cl solution (0.5 mL)
  7. customthen evaporated to dryness
  8. dissolutionThe resulting residue was dissolved in DMSO
  9. custompurified by reverse phase HPLC (ammonium formate buffer)

출처 및 근거

ORD 기록
ord-197c53574dd1404fa4837cdecc0c7a7a
출처 데이터셋
uspto-grants-2016_05
특허 번호
US09345708B2

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