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

反応式

HRID 1692875 の反応式
[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]

参加物

8

反応物 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

生成物 1

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

試薬・触媒・溶媒 3

HCID 887Methanol溶媒HCID 962Water溶媒HCID 6228Dimethylformamide溶媒

反応条件

温度
50 °C

実験手順

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.

後処理

  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)

出典と根拠

ORDレコード
ord-fee263cbc74249f58c2b8a1a1d2cf3b2
出典データセット
uspto-grants-2012_04
特許番号
US08158625B2

関連ノート

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