Diisopropylethylamine → 3-[3,3-difluoro-6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,6-diazaspiro[3.4]oct-1-yl]-3-oxopropionitrile

HRID 1912414ノート

反応式

HRID 1912414 の反応式
[F:1][C:2]1([F:19])[C:5]2([CH2:9][CH2:8][N:7]([C:10]3[C:11]4[CH:18]=[CH:17][NH:16][C:12]=4[N:13]=[CH:14][N:15]=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.C(N(CC)C(C)C)(C)C.C(=O)(O)[O-].[Na+]>O1CCOCC1>[F:19][C:2]1([F:1])[C:5]2([CH2:9][CH2:8][N:7]([C:10]3[C:11]4[CH:18]=[CH:17][NH:16][C:12]=4[N:13]=[CH:14][N:15]=3)[CH2:6]2)[N:4]([C:26](=[O:27])[CH2:28][C:29]#[N:30])[CH2:3]1

参加物

6

反応物 4

HCID 81531DiisopropylethylamineHCID 2621013-(3,5-Dimethyl-1H-pyrazol-1-yl)-3-oxopropanenitrileHCID 516892Sodium BicarbonateHCID 582933354-(3,3-difluoro-1,6-diazaspiro[3,4]oct-6-yl)-7H-pyrrolo[2,3-d]pyrimidine

生成物 1

HCID 509136233-[3,3-difluoro-6-(7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1,6-diazaspiro[3.4]oct-1-yl]-3-oxopropionitrile収率 83.1%

試薬・触媒・溶媒 1

HCID 312751,4-Dioxane溶媒

反応条件

温度
100 °C

実験手順

An optically-active compound of 4-(3,3-difluoro-1,6-diazaspiro[3,4]oct-6-yl)-7H-pyrrolo[2,3-d]pyrimidine (170 mg) was mixed with 1-cyanoacetyl-3,5-dimethylpyrazole (209 mg), N,N-diisopropylethylamine (117 μl) and 1,4-dioxane (3.4 ml), and the mixture was stirred at 100° C. for 75 minutes. The mixture was cooled to room temperature. Thereto was added saturated aqueous sodium bicarbonate solution, and the mixture was extracted with ethyl acetate. The separated aqueous layer was extracted with ethyl acetate twice again. The combined organic layer was washed with 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/ethyl acetate=2/1, followed by chloroform/methanol=92/8 to 3/1). The mixture was concentrated under reduced pressure, and the resulting residue was slurry-washed with a mixed solvent of n-heptane/ethanol (3/1) to give the titled compound (177 mg).

後処理

  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 twice again
  4. washThe combined organic layer was washed with 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/ethyl acetate=2/1, followed by chloroform/methanol=92/8 to 3/1)
  8. concentrationThe mixture was concentrated under reduced pressure
  9. washthe resulting residue was slurry-washed with a mixed solvent of n-heptane/ethanol (3/1)

出典と根拠

ORDレコード
ord-d8b6097f0a164959a322e57012dbeafb
出典データセット
uspto-grants-2013_12
特許番号
US08609647B2

反応ノート

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