Isopropanol → HCID 178503490、化合物

HRID 1091823

反応式

HRID 1091823 の反応式
Cl[C:2]1[N:7]=[C:6]([S:8][CH3:9])[N:5]=[C:4]([NH:10][C:11]2[NH:15][N:14]=[C:13]([CH3:16])[CH:12]=2)[CH:3]=1.Cl.[CH:18]1([C:21]2([F:25])[CH2:24][NH:23][CH2:22]2)[CH2:20][CH2:19]1.C(N(C(C)C)CC)(C)C.C(O)(C)C>CCCCCC>[CH:18]1([C:21]2([F:25])[CH2:24][N:23]([C:2]3[N:7]=[C:6]([S:8][CH3:9])[N:5]=[C:4]([NH:10][C:11]4[NH:15][N:14]=[C:13]([CH3:16])[CH:12]=4)[CH:3]=3)[CH2:22]2)[CH2:20][CH2:19]1

参加物

6

反応物 4

HCID 3776IsopropanolHCID 81531DiisopropylethylamineHCID 665896423-Cyclopropyl-3-fluoroazetidine hydrochlorideHCID 178418729HCID 178418729、化合物

生成物 1

HCID 178503490HCID 178503490、化合物収率 80%

試薬・触媒・溶媒 1

HCID 8058Hexane溶媒

反応条件

温度
85 °C

実験手順

To a mixture of 6-chloro-N-(3-methyl-1H-pyrazol-5-yl)-2-(methylthio)pyrimidin-4-amine (150 g, 0.58 mol), 3-cyclopropyl-3-fluoroazetidine hydrochloride (132.2 g, 0.87 mol) was added diisopropylethylamine (208 g, 1.61 mol) and isopropanol (1.125 L) and then heated to reflux for 23 hours. The reaction was cooled to slightly hazy solution to 85° C. and filtered and the homogeneous solution concentrated to a minimal volume. EtOAc was added (1 L) and concentrated to minimal volume. EtOAc (1 L) and H2O (1 L) were added and the layers separated (organic started to crystallize product during the extraction). The aqueous layer was further extracted with EtOAc (500 ml). Concentrated the 1st organic to dryness to give a white solid. Hexane (750 ml) was added to the 2nd organic extract and the slurry was stirred at ambient temperature, then cooled to 0° C. for 30 min. Filtered and washed with copious Heptane. The filter cake was dried under vacuum. The filter cake and the white solid from the 1st extraction were combined to afford 155.1 g of the desired product. (155.1 g, 77%). 1H NMR (DMSO, 400 MHz) 0.44 (2H, m), 0.60 (2H, m), 1.38-1.43 (1H, m), 2.18 (3H, s), 2.42 (3H, s), 3.89-3.97 (4H, m), 5.92 (1H, br s), 6.04 (1H, br s), 9.23 (1H, s), 11.86 (1H, s). ES+ 335

後処理

  1. temperatureheated
  2. temperatureto reflux for 23 hours
  3. filtrationfiltered
  4. concentrationthe homogeneous solution concentrated to a minimal volume
  5. additionEtOAc was added (1 L)
  6. concentrationconcentrated to minimal volume
  7. additionEtOAc (1 L) and H2O (1 L) were added
  8. customthe layers separated (
  9. customto crystallize product
  10. extractionduring the extraction)
  11. extractionThe aqueous layer was further extracted with EtOAc (500 ml)
  12. concentrationConcentrated the 1st organic to dryness
  13. customto give a white solid
  14. extractionorganic extract
  15. temperaturecooled to 0° C. for 30 min
  16. filtrationFiltered
  17. washwashed with copious Heptane
  18. customThe filter cake was dried under vacuum
  19. extractionThe filter cake and the white solid from the 1st extraction

出典と根拠

ORDレコード
ord-2d42c3b1a4f44aaba7f1bcdf958c7f18
出典データセット
uspto-grants-2012_03
特許番号
US08129399B2

関連ノート

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