반응 #69219

ord-fb7ee31ece0944d78d2cba46754bbf98

용매

반응 조건

온도
0°CELSIUS
상세 조건
See reaction.notes.procedure_details.

후처리

  1. 1
    기타the reaction to a dark solution
  2. 2
    농축The reaction was then concentrated
  3. 3
    기타to remove the DCM
  4. 4
    workup.ADDITIONthe resulting DMF solution was diluted with water
  5. 5
    기타to precipitate the product
  6. 6
    기타The solid precipitate was collected
  7. 7
    세척washed with water
  8. 8
    기타to give a dark solid
  9. 9
    세척washed with brine
  10. 10
    건조dried over magnesium sulfate
  11. 11
    농축concentrated
  12. 12
    기타to give a very dark oily residue
  13. 13
    workup.STIRRINGThis was stirred at rt
  14. 14
    기타to precipitate 3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]-pyrimidin-4-yl)-1H-pyrazol-1-yl]pentanedinitrile as white needle-like crystals (22.7 gm, 85%), LC /MS (M+H)+

실험 절차

3-[4-(7-[2-(Trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]pentanediamide (29.0 g, 0.0654 mol) was partially dissolved in DMF (200 mL, 2 mol), DCM (200 mL, 3 mol) and TEA (36 mL, 0.26 mol) and cooled in an ice bath under nitrogen atmosphere. The trichloroacetyl chloride (15 mL, 0.14 mol) was added dropwise turning the reaction to a dark solution. This was stirred at 0° C. for ½ h. The reaction was then concentrated to remove the DCM and the resulting DMF solution was diluted with water to precipitate the product. The solid precipitate was collected and washed with water to give a dark solid. The solid was then dissolved in DCM and washed with brine, dried over magnesium sulfate and concentrated to give a very dark oily residue. The residue was taken up in DCM, and hexane was added until the solution became slightly cloudy. This was stirred at rt to precipitate 3-[4-(7-[2-(trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]-pyrimidin-4-yl)-1H-pyrazol-1-yl]pentanedinitrile as white needle-like crystals (22.7 gm, 85%), LC /MS (M+H)+: 408, 1H NMR (DMSO-d6) δ 9.07(s, 1H), 8.87(s, 1H), 8.59(s, 1H), 7.88(d, 1H), 7.19(d, 1H), 5.75(s, 2H), 5.30(m,1H), 3.62(t, 2H), 3.40(m, 4H), 0.91(t, 2H), 0.10(s, 9H).

출처

DOI: 10.6084/m9.figshare.5104873.v1특허: US08530485B2uspto-grants-2013_09