Isobutyraldehyde → 1-(3-((tert-butyldimethylsilyl)oxy)propyl)-7-(4-chlorobenzyl)-8-(1-hydroxy-2-methylpropyl)-3-methyl-1H-purine-2,6(3H,7H)-dione

HRID 2200747ノート

反応式

HRID 2200747 の反応式
Br[C:2]1[N:10]([CH2:11][C:12]2[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=2)[C:9]2[C:8](=[O:19])[N:7]([CH2:20][CH2:21][CH2:22][O:23][Si:24]([C:27]([CH3:30])([CH3:29])[CH3:28])([CH3:26])[CH3:25])[C:6](=[O:31])[N:5]([CH3:32])[C:4]=2[N:3]=1.C([Li])CCC.[CH:38](=[O:42])[CH:39]([CH3:41])[CH3:40]>C1COCC1.O>[Si:24]([O:23][CH2:22][CH2:21][CH2:20][N:7]1[C:8](=[O:19])[C:9]2[N:10]([CH2:11][C:12]3[CH:17]=[CH:16][C:15]([Cl:18])=[CH:14][CH:13]=3)[C:2]([CH:38]([OH:42])[CH:39]([CH3:41])[CH3:40])=[N:3][C:4]=2[N:5]([CH3:32])[C:6]1=[O:31])([C:27]([CH3:29])([CH3:30])[CH3:28])([CH3:25])[CH3:26]

参加物

6

反応物 3

HCID 6561IsobutyraldehydeHCID 904028568-bromo-1-(3-((tert-butyldimethylsilyl)oxy)propyl)-7-(4-chlorobenzyl)-3-methyl-3,7-dihydro-1H-purine-2,6-dione2 回HCID 178418339Butyllithium

生成物 1

HCID 904029981-(3-((tert-butyldimethylsilyl)oxy)propyl)-7-(4-chlorobenzyl)-8-(1-hydroxy-2-methylpropyl)-3-methyl-1H-purine-2,6(3H,7H)-dione収率 40.5%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 8028Tetrahydrofuran溶媒2 回

反応条件

温度
-78 °C

実験手順

Step 1 8-Bromo-1-(3-((tert-butyldimethylsilyl)oxy)propyl-7-(4-chlorobenzyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (0.50 g, 0.923 mmol, intermediate 77) was dissolved in THF (5 mL) and cooled to −78° C. To the clear solution was slowly added drop wise 2.5 M n-butyllithium in THF (0.35 mL, 0.877 mmol) followed by the immediate addition of isobutyraldehyde (0.42 mL, 4.61 mmol). The reaction was warmed to room temperature and stirred for 1 h. The reaction was diluted with water (75 mL) and extracted with ethyl acetate (3×75 mL). The combined extracts were dried with magnesium sulfate, filtered and the solvent was removed under reduced pressure to yield an oil. The oil was purified using a 25 g silica column eluted with a gradient of 10% to 30% ethyl acetate/hexanes yielding 1-(3-((tert-butyldimethylsilyl)oxy)propyl)-7-(4-chlorobenzyl)-8-(1-hydroxy-2-methylpropyl)-3-methyl-1H-purine-2,6(3H,7H)-dione (0.20 g, 40% yield) as a light golden oil. LCMS retention time=4.923 min and 98% purity, LCMS MH+ 535.

後処理

  1. temperatureThe reaction was warmed to room temperature
  2. extractionextracted with ethyl acetate (3×75 mL)
  3. dry with materialThe combined extracts were dried with magnesium sulfate
  4. filtrationfiltered
  5. customthe solvent was removed under reduced pressure
  6. customto yield an oil
  7. customThe oil was purified
  8. washeluted with a gradient of 10% to 30% ethyl acetate/hexanes

出典と根拠

ORDレコード
ord-4751f8b27b484d48b8cf038394e2a0f0
出典データセット
uspto-grants-2016_06
特許番号
US09359359B2

反応ノート

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