Tetrahydrofuran → HCID 19356091, compound

HRID 377615Notes

Reaction equation

HRID 377615 reaction equation
C([N-]C(C)C)(C)C.[Li+].[CH3:9][N:10]1[C:15](=[O:16])[C:14]2=[CH:17][N:18]([CH2:20][C:21]3[C:30]4[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=4)[CH:24]=[CH:23][CH:22]=3)[N:19]=[C:13]2[N:12]([CH2:31][CH:32]([CH3:34])[CH3:33])[C:11]1=[O:35].CC1C=CC([S:43](OCCCO[Si](C)(C)C(C)(C)C)(=O)=S)=CC=1.[O:58]1C[CH2:61][CH2:60][CH2:59]1>>[OH:58][CH2:59][CH2:60][CH2:61][S:43][C:17]1[N:18]([CH2:20][C:21]2[C:30]3[C:25](=[CH:26][CH:27]=[CH:28][CH:29]=3)[CH:24]=[CH:23][CH:22]=2)[N:19]=[C:13]2[C:14]=1[C:15](=[O:16])[N:10]([CH3:9])[C:11](=[O:35])[N:12]2[CH2:31][CH:32]([CH3:33])[CH3:34]

Participants

5

Reactant 4

HCID 8028TetrahydrofuranHCID 2724682Lithium diisopropylamideHCID 19356079HCID 19356079, compoundHCID 53747051HCID 53747051, compound

Product 1

HCID 19356091HCID 19356091, compound

Conditions

Temperature
-78 °C

Procedure

Lithium diisopropylamide (3.3 mmol) was added to a solution of 5-methyl-7-(2-methylpropyl)-2-(1-naphthalenylmethyl)-2H-pyrazolo[3,4-d]pyrimidine-4,6(5H,7H)dione (600 mg) and 3-{[dimethyl(1,1-dimethylethyl)silyl]oxy }propyl 4-methylphenylthiosulfonate (J. Med. Chem. 1995, 38, 2557) (720 mg) in tetrahydrofuran (20 ml) cooled to -78° C. After 2 hours the reaction mixture was warmed to ambient temperature and after a further hour quenched with water. The reaction mixture was diluted with ethyl acetate and was washed twice with dilute hydrochloric acid, twice with saturated sodium hydrogen carbonate solution, once with brine, and then dried over magnesium sulfate, filtered and concentrated. The residue was dissolved in tetrahydrofuran (20 ml) and tetrabutylammonium fluoride (1 M in tetrahydrofuran, 2 ml) was added. After 18 hours the reaction mixture was quenched with saturated sodium hydrogen carbonate solution and extracted with ether. The ether extract was washed once with water and once with brine, then dried over magnesium sulfate, filtered and concentrated. Chromatography of the residue on silica gel (isohexane:ethyl acetate 1:1-1:2) followed by preparative reverse phase HPLC and recrystallisation from isohexane : ethyl acetate gave the title compound (156 mg).

Workup

  1. temperatureAfter 2 hours the reaction mixture was warmed to ambient temperature and after a further hour
  2. customquenched with water
  3. additionThe reaction mixture was diluted with ethyl acetate
  4. washwas washed twice with dilute hydrochloric acid, twice with saturated sodium hydrogen carbonate solution, once with brine
  5. dry with materialdried over magnesium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated
  8. dissolutionThe residue was dissolved in tetrahydrofuran (20 ml)
  9. additiontetrabutylammonium fluoride (1 M in tetrahydrofuran, 2 ml) was added
  10. customAfter 18 hours the reaction mixture was quenched with saturated sodium hydrogen carbonate solution
  11. extractionextracted with ether
  12. extractionThe ether extract
  13. washwas washed once with water and once with brine
  14. dry with materialdried over magnesium sulfate
  15. filtrationfiltered
  16. concentrationconcentrated
  17. customChromatography of the residue on silica gel (isohexane:ethyl acetate 1:1-1:2) followed by preparative reverse phase HPLC and recrystallisation from isohexane

Sources & evidence

ORD record
ord-810c47ffbba84f12aea440f8c3d03b1f
Source dataset
uspto-grants-2000_02
Patent number
US06028074

Reaction notes

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