Ammonia → 4-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine

HRID 1011292Notes

Reaction equation

HRID 1011292 reaction equation
[Cl:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[NH:8][N:9]=[CH:10][C:3]=12.[C:11]1(C)C=[CH:15][C:14](S(O)(=O)=O)=[CH:13][CH:12]=1.N.C(OCC)(=[O:25])C>>[Cl:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:15]3[CH2:14][CH2:13][CH2:12][CH2:11][O:25]3)[N:9]=[CH:10][C:3]=12

Participants

5

Reactant 4

HCID 222AmmoniaHCID 6101p-Toluenesulfonic acidHCID 8857Ethyl AcetateHCID 2210954-Chloro-1H-pyrazolo[3,4-d]pyrimidine

Product 1

HCID 2394984-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidineYield 77%

Conditions

Temperature
50 °C

Procedure

To a round bottom flask equipped with a magnetic stir bar was added 4-chloro-1H-pyrazolo[3,4-d]pyrimidine (2.0 g, 12.9 mmol, 1.0 eq.) and ethyl acetate. The mixture was heated to 50° C. After 10 minutes p-toluenesulfonic acid (50 mg) was added, followed by the addition of 2,3-dihydropurane (1.09 g, 15.5 mmol, 1.2 eq). The resulting reaction mixture was heated at 50° C. with stirring for 1 hour and was then cooled to room temperature at which time aqueous ammonia was added. After 5 minutes the organic layer was separated, and washed twice with water (100 ml) and once with brine (100 ml). The ethyl acetate was removed and petroleum ether was added. The mixture was heated and filtered thru cotton. Removal of the petroleum ether in vacuo afforded 4-chloro-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine as a light yellow colored solid (2.35 g, 77%). 1H NMR (400 MHz, CDCl3): 8.81(s, 1H), 8.22 (s, 1H), 6.05 (dd, 1H), 4.14 (m, 1H), 3.81 (m, 1H), 2.61 (m, 1H), 2.14 (m, 1H), 1.99 (m, 1H), 1.81 (m, 2H), 1.64 (m, 1H); MS (ESI) for C10H11ClN4O: 239 (MH+).

Workup

  1. customTo a round bottom flask equipped with a magnetic stir bar
  2. additionfollowed by the addition of 2,3-dihydropurane (1.09 g, 15.5 mmol, 1.2 eq)
  3. customThe resulting reaction mixture
  4. temperaturewas heated at 50° C.
  5. additionwas added
  6. customAfter 5 minutes the organic layer was separated
  7. washwashed twice with water (100 ml) and once with brine (100 ml)
  8. customThe ethyl acetate was removed
  9. additionpetroleum ether was added
  10. temperatureThe mixture was heated
  11. filtrationfiltered
  12. customRemoval of the petroleum ether in vacuo

Sources & evidence

ORD record
ord-ec902a0a7a4e4a3db46592aa6387ea73
Source dataset
uspto-grants-2011_07
Patent number
US07977345B2

Reaction notes

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