Ethanol → (2,3-Dihydro-Benzo[1,4]dioxin-6-yl methyl)-[1-(3,5-dimethyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine

HRID 1801684

反応式

HRID 1801684 の反応式
C(O)C.Cl[C:5]1[N:10]=[CH:9][N:8]=[C:7]2[N:11]([C:14]3[CH:19]=[C:18]([CH3:20])[CH:17]=[C:16]([CH3:21])[CH:15]=3)[N:12]=[CH:13][C:6]=12.Cl.[O:23]1[C:28]2[CH:29]=[CH:30][C:31](NC)=[CH:32][C:27]=2[O:26][CH2:25][CH2:24]1.[CH2:35]([N:37](CC)CC)C>>[O:23]1[C:28]2[CH:29]=[CH:30][C:31]([CH2:35][NH:37][C:5]3[N:10]=[CH:9][N:8]=[C:7]4[N:11]([C:14]5[CH:19]=[C:18]([CH3:20])[CH:17]=[C:16]([CH3:21])[CH:15]=5)[N:12]=[CH:13][C:6]=34)=[CH:32][C:27]=2[O:26][CH2:25][CH2:24]1

参加物

5

反応物 4

HCID 702EthanolHCID 8471TriethylamineHCID 49621194-chloro-1-(3,5-dimethylphenyl)-1H-pyrazolo[3,4-d]pyrimidineHCID 46735896N-methyl-2,3-dihydro-1,4-benzodioxin-6-amine hydrochloride

生成物 1

HCID 44182507(2,3-Dihydro-Benzo[1,4]dioxin-6-yl methyl)-[1-(3,5-dimethyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl]-amine収率 86%

反応条件

温度
27.5 °C

実験手順

350.0 ml of ethanol and 25.0 g (0.096 mol) of 4-chloro-1-(3,5-dimethyl-phenyl)-1H-pyrazolo[3,4-d]pyrimidine (Compound No. 79) were charged into a 1.0 L 4 necked round bottom flask connected to a mechanical stirrer, thermometer socket, condenser and addition funnel. Stirred the mass at 25-30° C. for 15-20 min. 32.0 g of 2,3-dihydro-benzo[1,4]dioxin-6-yl-methylamine hydrochloride was charged at 25-30° C. under stirring. Stirred the mass at 25-30° C. for 15-20 min. 30.0 g of triethyl amine was added slowly at maintaining the mass temperature 25-30° C. during 30-45 min. Maintained the mass temperature at 25-30° C. for 30-45 min. Temperature of the reaction mass was raised to refluxing. Maintained the mass at reflux temperature for 10-11 hours. Reaction mass was cooled to 25-30° C. Maintained the mass temperature at 25-30° C. for 60-90 min. Reaction mass was cooled to 0-5° C. Maintained the mass temperature at 0-5° C. for 90-120 min. Solid was filtered and washed with 50.0 ml of chilled ethanol. Compound was dried under vacuum at 60-65° C. till constant weight is obtained. Dry weight of the compound is 35.50 g. 175.0 ml of dimethyl sulphoxide and 35.50 g of dry crude compound were charged into a 1.0 L 4-necked round bottom flask, connected to a mechanical stirrer, thermometer socket and condenser. Mass temperature was raised to 55-60° C. Maintained the mass temperature at 55-60° C. for 30-45 min. Insoluble solid was filtered through hyflow bed, washed the flask with 20.00 ml of hot dimethyl sulphoxide. Clear aerate was collected into flask. 1000.0 ml of Water is charged into a 3.0 L 4 necked round bottom flask, connected to a mechanical stirrer, thermo meter socket and addition funnel. Dimethyl sulphoxide solution was added slowly to water at maintaining the mass temperature at 25-35° C. over a period of 30-45 min. Maintained the mass temperature at 25-35° C. for 60-90 min. Temperature of the mass was cooled to 5-10° C. Maintained the mass temperature at 5-10° C. for 90-120 min. Solid was filtered and solid was washed with 150 ml of water. Compound was dried under vacuum at 60-65° C. 32.0 g Of dried compound is obtained (yield—85.5% by theory). Product purity by HPLC is 99.48%.

後処理

  1. customconnected to a mechanical stirrer
  2. additionthermometer socket, condenser and addition funnel
  3. stirringunder stirring
  4. stirringStirred the mass at 25-30° C. for 15-20 min
  5. temperatureat maintaining the mass temperature 25-30° C. during 30-45 min
  6. temperatureMaintained the mass temperature at 25-30° C. for 30-45 min
  7. temperatureTemperature of the reaction mass was raised
  8. temperatureto refluxing
  9. temperatureMaintained the mass
  10. temperatureat reflux temperature for 10-11 hours
  11. customReaction mass
  12. temperaturewas cooled to 25-30° C
  13. temperatureMaintained the mass temperature at 25-30° C. for 60-90 min
  14. customReaction mass
  15. temperaturewas cooled to 0-5° C
  16. temperatureMaintained the mass temperature at 0-5° C. for 90-120 min
  17. filtrationSolid was filtered
  18. washwashed with 50.0 ml of chilled ethanol
  19. customCompound was dried under vacuum at 60-65° C. till constant weight
  20. customis obtained
  21. customDry weight of the compound
  22. dry with material175.0 ml of dimethyl sulphoxide and 35.50 g of dry crude compound
  23. additionwere charged into a 1.0 L 4-necked round bottom flask
  24. customconnected to a mechanical stirrer
  25. temperatureMass temperature was raised to 55-60° C
  26. temperatureMaintained the mass temperature at 55-60° C. for 30-45 min
  27. filtrationInsoluble solid was filtered through hyflow bed
  28. washwashed the flask with 20.00 ml of hot dimethyl sulphoxide
  29. customClear aerate was collected into flask
  30. addition1000.0 ml of Water is charged into a 3.0 L 4 necked round bottom flask
  31. customconnected to a mechanical stirrer
  32. additionthermo meter socket and addition funnel
  33. additionDimethyl sulphoxide solution was added slowly to water
  34. temperatureat maintaining the mass temperature at 25-35° C. over a period of 30-45 min
  35. temperatureMaintained the mass temperature at 25-35° C. for 60-90 min
  36. temperatureTemperature of the mass was cooled to 5-10° C
  37. temperatureMaintained the mass temperature at 5-10° C. for 90-120 min
  38. filtrationSolid was filtered
  39. washsolid was washed with 150 ml of water
  40. customCompound was dried under vacuum at 60-65° C

出典と根拠

ORDレコード
ord-489353c7c4304b95a426d471ace1e9c2
出典データセット
uspto-grants-2013_01
特許番号
US08349847B2

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