تفاعل #69219

معادلة التفاعل

trichloroacetyl chloride

3-[4-(7-[2-(Trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]pentanediamide

DMF

hexane

→

3-[4-(7-[2-(Trimethylsilyl)ethoxy]methyl-7H-pyrrolo[2,3-d]pyrimidin-4-yl)-1H-pyrazol-1-yl]-pentanedinitrile

المذيبات

DCM

DCM

DCM

ظروف التفاعل

المعالجة

1. 1
   أخرىthe reaction to a dark solution
2. 2
   تركيزThe reaction was then concentrated
3. 3
   أخرىto remove the DCM
4. 4
   workup.ADDITIONthe resulting DMF solution was diluted with water
5. 5
   أخرىto precipitate the product
6. 6
   أخرىThe solid precipitate was collected
7. 7
   غسيلwashed with water
8. 8
   أخرىto give a dark solid
9. 9
   غسيلwashed with brine
10. 10
    تجفيفdried over magnesium sulfate
11. 11
    تركيزconcentrated
12. 12
    أخرىto give a very dark oily residue
13. 13
    workup.STIRRINGThis was stirred at rt
14. 14
    أخرىto 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)+

الإجراء التجريبي

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).

المصدر