Acetic Acid → 4-chloro-5-iodo-7-[1-(1-methyl-4-piperidinyl)-4-piperidinyl]-7H-pyrrolo[2,3-d]pyrimidine

HRID 51616

反応式

HRID 51616 の反応式
[Cl:1][C:2]1[C:3]2[C:10]([I:11])=[CH:9][N:8]([CH:12]3[CH2:17][CH2:16][NH:15][CH2:14][CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1.[CH3:18][N:19]1[CH2:24][CH2:23][C:22](=O)[CH2:21][CH2:20]1.C(O)(=O)C.C(O[BH-](OC(=O)C)OC(=O)C)(=O)C.[Na+].C(=O)(O)[O-].[Na+]>ClC(Cl)C.O>[Cl:1][C:2]1[C:3]2[C:10]([I:11])=[CH:9][N:8]([CH:12]3[CH2:17][CH2:16][N:15]([CH:22]4[CH2:23][CH2:24][N:19]([CH3:18])[CH2:20][CH2:21]4)[CH2:14][CH2:13]3)[C:4]=2[N:5]=[CH:6][N:7]=1

参加物

8

反応物 5

HCID 176Acetic Acid2 回HCID 740491-Methyl-4-piperidone2 回HCID 516892Sodium BicarbonateHCID 5049666Sodium triacetoxyborohydrideHCID 227362064-chloro-5-iodo-7-(4-piperidyl)-7H-pyrrolo[2,3-d]pyrimidine

生成物 1

HCID 227361824-chloro-5-iodo-7-[1-(1-methyl-4-piperidinyl)-4-piperidinyl]-7H-pyrrolo[2,3-d]pyrimidine収率 61%

試薬・触媒・溶媒 2

HCID 962Water溶媒HCID 63651,1-Dichloroethane溶媒

反応条件

温度
0 °C

実験手順

A mixture of 4-chloro-5-iodo-7-(4-piperidinyl)-7H-pyrrolo[2,3-d]pyrimidine (0.52 g, 1.43 mmol), 1-methyl-4-piperidone (0.178 g, 1.57 mmol), and glacial acetic acid (0.094 g, 1.57 mmol) in dichloroethane was stirred at 0° C. for 20 minutes. Sodium 15 triacetoxy borohydride (0.455 g, 2.15 mmol) was added and stirred for 15 minutes at 0° C., after which the ice bath was removed, allowed to warm to room temperature and stirred over night. Additional 1-methyl-4-piperidone (0.178 g, 1.57 mmol), glacial acetic acid (0.094 g, 1.57 mmol), and sodium triacetoxy borohydride (0.455 g, 2.15 mmol) were added and stirred at room temperature. To the reaction solution was added sodium bicarbonate (0.721 g, 8.58 mmol) in water (10 mL) and stirred for 1 hour. The organic layer was evaporated under reduced pressure. Ethyl acetate was added, the layers were partitioned, and the aqueous layer was extracted with ethyl acetate. The organic layers were combined, washed with water and brine, dried over magnesium sulfate, filtered and evaporated under reduced pressure. The compound was purified by flash chromatography on silica using dichloromethane/ethyl acetate (1:1), 10% methanol in dichloromethane, and then 20% methanol in dichloromethane to give 400 mg (61%) of 4-chloro-5-iodo-7-[1-(1-methyl-4-piperidinyl)-4-piperidinyl]-7H-pyrrolo[2,3-d]pyrimidine

後処理

  1. stirringstirred for 15 minutes at 0° C.
  2. customafter which the ice bath was removed
  3. temperatureto warm to room temperature
  4. stirringstirred over night
  5. stirringstirred at room temperature
  6. stirringstirred for 1 hour
  7. customThe organic layer was evaporated under reduced pressure
  8. additionEthyl acetate was added
  9. customthe layers were partitioned
  10. extractionthe aqueous layer was extracted with ethyl acetate
  11. washwashed with water and brine
  12. dry with materialdried over magnesium sulfate
  13. filtrationfiltered
  14. customevaporated under reduced pressure
  15. customThe compound was purified by flash chromatography on silica

出典と根拠

ORDレコード
ord-106d473a23f243a7be95a35f3e678cc3
出典データセット
uspto-grants-2004_03
特許番号
US06713474B2

関連ノート

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