Hydrochloric Acid → 2-(2-chloro-8-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-6-morpholino-9H-purin-9-yl)ethyl acetate

HRID 1692875

반응식

HRID 1692875 반응식
[Cl:1][C:2]1[N:10]=[C:9]2[C:5]([N:6]=[C:7]([CH2:17][N:18]3[CH2:23][CH2:22][CH:21]([C:24]([OH:27])([CH3:26])[CH3:25])[CH2:20][CH2:19]3)[N:8]2C2CCCCO2)=[C:4]([N:28]2[CH2:33][CH2:32][O:31][CH2:30][CH2:29]2)[N:3]=1.Cl.[H-].[Na+].[C:37]([O:40][CH2:41][CH2:42]Br)(=[O:39])[CH3:38]>CO.CN(C=O)C.O>[C:37]([O:40][CH2:41][CH2:42][N:8]1[C:7]([CH2:17][N:18]2[CH2:23][CH2:22][CH:21]([C:24]([OH:27])([CH3:26])[CH3:25])[CH2:20][CH2:19]2)=[N:6][C:5]2[C:9]1=[N:10][C:2]([Cl:1])=[N:3][C:4]=2[N:28]1[CH2:29][CH2:30][O:31][CH2:32][CH2:33]1)(=[O:39])[CH3:38]

참가 물질

8

반응물 4

HCID 313Hydrochloric AcidHCID 135641-Acetoxy-2-bromoethaneHCID 24758Sodium hydrideHCID 596035392-(1-((2-chloro-6-morpholino-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-8-yl)methyl)piperidin-4-yl)propan-2-ol

생성물 1

HCID 866481532-(2-chloro-8-((4-(2-hydroxypropan-2-yl)piperidin-1-yl)methyl)-6-morpholino-9H-purin-9-yl)ethyl acetate수율 33.4%

시약·촉매·용매 3

HCID 887Methanol용매HCID 962Water용매HCID 6228Dimethylformamide용매

반응 조건

온도
50 °C

실험 절차

To a solution of 2-(1-((2-chloro-6-morpholino-9-(tetrahydro-2H-pyran-2-yl)-9H-purin-8-yl)methyl)piperidin-4-yl)propan-2-ol (328 mg, 0.685 mmol) in methanol (10 mL) was added concentrated HCl (0.15 mL). The resulting mixture was stirred at 50° C. for 18 hours. The reaction mixture was then concentrated to give a yellow paste which was then taken up in DMF (10 mL) and cooled to 0° C. To this cooled solution was then added sodium hydride (60% dispersion, 88 mg, 2.2 mmol). The mixture was stirred at 0° C. for 5 minutes before the addition of 2-bromoethanol acetate (0.2 mL, 1.8 mmol). After 18 hours of stirring at room temperature, the reaction was diluted with water. The aqueous mixture was the extracted three times with EtOAc. The combined extracts were washed with brine, dried over Na2SO4, filtered and concentrated. The crude product was purified by flash chromatography (10% MeOH in DCM) to give the title compound (110 mg, 26%). LCMS: M+H+=481.2.

후처리

  1. concentrationThe reaction mixture was then concentrated
  2. customto give a yellow paste which
  3. temperaturecooled to 0° C
  4. stirringAfter 18 hours of stirring at room temperature
  5. extractionextracted three times with EtOAc
  6. washThe combined extracts were washed with brine
  7. dry with materialdried over Na2SO4
  8. filtrationfiltered
  9. concentrationconcentrated
  10. customThe crude product was purified by flash chromatography (10% MeOH in DCM)

출처 및 근거

ORD 기록
ord-fee263cbc74249f58c2b8a1a1d2cf3b2
출처 데이터셋
uspto-grants-2012_04
특허 번호
US08158625B2

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