1,4-Dioxane → CID 50913770

HRID 1912423Notes

Reaction equation

HRID 1912423 reaction equation
[F:1][C:2]1([F:20])[C:5]2([CH2:10][CH2:9][CH2:8][N:7]([C:11]3[C:12]4[CH:19]=[CH:18][NH:17][C:13]=4[N:14]=[CH:15][N:16]=3)[CH2:6]2)[NH:4][CH2:3]1.CC1N([C:27]([CH2:29][C:30]#[N:31])=[O:28])N=C(C)C=1.C(N(CC)C(C)C)(C)C.O1CCOCC1>O>[F:20][C:2]1([F:1])[C:5]2([CH2:10][CH2:9][CH2:8][N:7]([C:11]3[C:12]4[CH:19]=[CH:18][NH:17][C:13]=4[N:14]=[CH:15][N:16]=3)[CH2:6]2)[N:4]([C:27](=[O:28])[CH2:29][C:30]#[N:31])[CH2:3]1

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 81531DiisopropylethylamineHCID 2621013-(3,5-Dimethyl-1H-pyrazol-1-yl)-3-oxopropanenitrileHCID 582934094-(3,3-difluoro-1,6-diaza-spiro[3.5]non-6-yl)-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 50913770CID 50913770Yield 91.6%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

An optically-active compound of 4-(3,3-difluoro-1,6-diaza-spiro[3.5]non-6-yl)-7H-pyrrolo[2,3-d]pyrimidine (6.6 g) was mixed with 1-cyanoacetyl-3,5-dimethylpyrazole (7.7 g), N,N-diisopropylethylamine (4.3 ml) and 1,4-dioxane (132 ml), and the mixture was stirred at 100° C. for 2 hours. The mixture was cooled to room temperature. Then, thereto was added water, and the mixture was extracted with ethyl acetate. The separated aqueous layer was further extracted with ethyl acetate 5 times. The combined organic layer was sequentially washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution, dried over anhydrous sodium sulfate and concentrated under reduced pressure. The resulting residue was purified by silica gel column chromatography (eluent: chloroform/acetone=3/2 to 2/3). To the resulting residue was added n-heptane, and the mixture was concentrated under reduced pressure. To the resulting residue was added diethylether, and the mixture was slurry-washed and filtered to give a solid (7.5 g). The filtrate was concentrated under reduced pressure. To the resulting residue was added diethylether, and the mixture was slurry-washed to give a solid (0.2 g). The combined solid was purified by silica gel column chromatography (eluent: chloroform/methanol=97/3 to 9/1). To the resulting solid was added ethanol, and the mixture was concentrated under reduced pressure to give the titled compound (7.1 g).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionthe mixture was extracted with ethyl acetate
  3. extractionThe separated aqueous layer was further extracted with ethyl acetate 5 times
  4. washThe combined organic layer was sequentially washed with saturated aqueous sodium bicarbonate solution and saturated aqueous sodium chloride solution
  5. dry with materialdried over anhydrous sodium sulfate
  6. concentrationconcentrated under reduced pressure
  7. customThe resulting residue was purified by silica gel column chromatography (eluent: chloroform/acetone=3/2 to 2/3)
  8. additionTo the resulting residue was added n-heptane
  9. concentrationthe mixture was concentrated under reduced pressure
  10. additionTo the resulting residue was added diethylether
  11. washthe mixture was slurry-washed
  12. filtrationfiltered

Sources & evidence

ORD record
ord-81b30cc4e80a4a11956283646d44ed6d
Source dataset
uspto-grants-2013_12
Patent number
US08609647B2

Reaction notes

Loading…