1,4-Dioxane → Jak3-IN-7

HRID 1912397Notes

Reaction equation

HRID 1912397 reaction equation
[CH3:1][CH:2]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)[NH:4][CH2:3]1.CC1N([C:26]([CH2:28][C:29]#[N:30])=[O:27])N=C(C)C=1.O1CCOCC1.C(=O)(O)[O-].[Na+]>O>[CH3:1][CH:2]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:26](=[O:27])[CH2:28][C:29]#[N:30])[CH2:3]1

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 2621013-(3,5-Dimethyl-1H-pyrazol-1-yl)-3-oxopropanenitrileHCID 516892Sodium BicarbonateHCID 582933114-(3-methyl-1,6-diazaspiro[3.5]non-6-yl)-7H-pyrrolo[2,3-d]pyrimidine

Product 1

HCID 50913620Jak3-IN-7Yield 21.3%

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
100 °C

Procedure

An optically-active compound of 4-(3-methyl-1,6-diazaspiro[3.5]non-6-yl)-7H-pyrrolo[2,3-d]pyrimidine (25 mg) was mixed with 1-cyanoacetyl-3,5-dimethylpyrazole (32 mg) and 1,4-dioxane (750 μl), and the mixture was stirred at 100° C. for 3.5 hours. The mixture was cooled to room temperature. Thereto were added water and saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The separated aqueous layer was extracted with ethyl acetate five times, and the combined organic layer was washed with water and concentrated under reduced pressure. The resulting residue was purified by silica-gel thin layer chromatography (eluent: chloroform/methanol=9/1). The resulting residue was purified by silica-gel thin layer chromatography (eluent: ethyl acetate/methanol=93/7) again. The resulting solid (8.0 mg) was slurry-washed with n-hexane/ethyl acetate solution to give the titled compound (6.7 mg).

Workup

  1. temperatureThe mixture was cooled to room temperature
  2. extractionthe mixture was extracted with ethyl acetate
  3. extractionThe separated aqueous layer was extracted with ethyl acetate five times
  4. washthe combined organic layer was washed with water
  5. concentrationconcentrated under reduced pressure
  6. customThe resulting residue was purified by silica-gel thin layer chromatography (eluent: chloroform/methanol=9/1)
  7. customThe resulting residue was purified by silica-gel thin layer chromatography (eluent: ethyl acetate/methanol=93/7) again
  8. washThe resulting solid (8.0 mg) was slurry-washed with n-hexane/ethyl acetate solution

Sources & evidence

ORD record
ord-bf60f4d017d84c879a65993acc105b20
Source dataset
uspto-grants-2013_12
Patent number
US08609647B2

Reaction notes

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