Ammonium Chloride → 7-(1-Propyl-butyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine

HRID 1660733ノート

反応式

HRID 1660733 の反応式
[Mg].Br[CH:3]([CH2:7][CH2:8][CH3:9])[CH2:4][CH2:5][CH3:6].Cl[C:11]1[N:16]2[N:17]=[C:18]([CH3:20])[CH:19]=[C:15]2[N:14]=[C:13]([CH3:21])[CH:12]=1.[Cl-].[NH4+]>C1COCC1.BrC(CCC)CCC.II>[CH2:4]([CH:3]([C:11]1[N:16]2[N:17]=[C:18]([CH3:20])[CH:19]=[C:15]2[N:14]=[C:13]([CH3:21])[CH:12]=1)[CH2:7][CH2:8][CH3:9])[CH2:5][CH3:6]

参加物

8

反応物 4

HCID 25517Ammonium ChlorideHCID 704604-BromoheptaneHCID 5462224Magnesium2 回HCID 184069877-Chloro-2,5-dimethylpyrazolo(1,5-a)pyrimidine

生成物 1

HCID 248985217-(1-Propyl-butyl)-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine収率 1,086.8%

試薬・触媒・溶媒 3

HCID 807Iodine触媒HCID 704604-Bromoheptane触媒HCID 8028Tetrahydrofuran溶媒3 回

反応条件

温度
0 °C

実験手順

Heat a mixture of magnesium turnings (3.5 g, 144 mmol) and a catalytic amount of iodine (100 mg) in THF (100 mL) to 65° C. under a nitrogen atmosphere. Add a few drops of neat 4-bromoheptane and heat the mixture until the reaction starts. Then add a solution of 4-bromoheptane (17.6 mL, 94 9 mmol) in THF (42 mL) keeping the temperature at 65-70° C. over 2 h. Reflux the mixture for an additional hour and then cool the reaction to 22° C. Add the prepared Grignard reagent to a solution of 7-chloro-2,5-dimethyl-pyrazolo[1,5-a]pyrimidine (10.2 g; 53 3 mmol) in THF (60 mL) cooled to 0° C. under a nitrogen atmosphere. Add the magnesium reagent solution via cannula over 45 min while keeping the temperature below 10° C. Then stir the mixture for an additional 30 min at 5° C. Add to this mixture a 10% aqueous ammonium chloride solution (wt/wt) (125 mL) and stir at 22° C. for 30 min. Separate the organic layer and extract the aqueous layer with ethyl acetate (2×25 mL). Combine the organic layers and dry over sodium sulfate. Filter the mixture and evaporate the solvent. Purify the crude material by silica gel flash chromatography using an eluent of hexanes/ethyl acetate (5/1) to provide the title compound (8 g, 62%). ES/MS m/z 246 (M+1)+.

後処理

  1. temperatureHeat
  2. customto 65° C.
  3. temperatureheat the mixture until the reaction
  4. customat 65-70° C.
  5. customover 2 h
  6. temperatureReflux the mixture for an additional hour
  7. temperaturecool
  8. customthe reaction to 22° C
  9. customthe temperature below 10° C
  10. stirringstir at 22° C. for 30 min
  11. customSeparate the organic layer
  12. extractionextract the aqueous layer with ethyl acetate (2×25 mL)
  13. dry with materialCombine the organic layers and dry over sodium sulfate
  14. filtrationFilter the mixture
  15. customevaporate the solvent
  16. customPurify the crude material by silica gel flash chromatography

出典と根拠

ORDレコード
ord-ecf40c43b84e46a59e3ace2e80a87c17
出典データセット
uspto-grants-2011_10
特許番号
US08030304B2

反応ノート

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