Lithium Hydroxide → 2-tert-Butyl-4-cyclobutyl-6-{4-[3-(pyridin-4-ylsulfanyl)-propyl]-piperazin-1-yl}-pyrimidine hydrochloride

HRID 219719ノート

反応式

HRID 219719 の反応式
[SH:1][C:2]1[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=1.[OH-].[Li+].[I-].[Na+].[C:12]([C:16]1[N:21]=[C:20]([N:22]2[CH2:27][CH2:26][N:25]([CH2:28][CH2:29][CH2:30][Cl:31])[CH2:24][CH2:23]2)[CH:19]=[C:18]([CH:32]2[CH2:35][CH2:34][CH2:33]2)[N:17]=1)([CH3:15])([CH3:14])[CH3:13]>CN(C)C=O>[ClH:31].[C:12]([C:16]1[N:17]=[C:18]([CH:32]2[CH2:33][CH2:34][CH2:35]2)[CH:19]=[C:20]([N:22]2[CH2:27][CH2:26][N:25]([CH2:28][CH2:29][CH2:30][S:1][C:2]3[CH:7]=[CH:6][N:5]=[CH:4][CH:3]=3)[CH2:24][CH2:23]2)[N:21]=1)([CH3:15])([CH3:13])[CH3:14]

参加物

6

反応物 4

HCID 3939Lithium HydroxideHCID 5238Sodium IodideHCID 666731042-tert-Butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-cyclobutyl-pyrimidineHCID 178418431pyridine-4-thiol

生成物 1

HCID 690805262-tert-Butyl-4-cyclobutyl-6-{4-[3-(pyridin-4-ylsulfanyl)-propyl]-piperazin-1-yl}-pyrimidine hydrochloride収率 129.8%

試薬・触媒・溶媒 1

HCID 6228Dimethylformamide溶媒

反応条件

温度
70 °C

実験手順

0.21 g of 4-mercapto-pyridine (1.8 mmol) were dissolved in 15 ml of dimethylformamide. After addition of 0.04 g of lithium hydroxide (1.8 mmol) and 0.13 g of sodium iodide (0.9 mmol), the reaction mixture was stirred at 70° C. and 0.63 g of 2-tert-butyl-4-[4-(3-chloro-propyl)-piperazin-1-yl]-6-cyclobutyl-pyrimidine (0.9 mmol) were added in portions. The mixture was stirred at 80° C. for 2 h, and after evaporation of dimethylformamide, partitioned between 20 ml of ethyl acetate and 15 ml of saturated aqueous sodium chloride solution and 15 ml of water. The aqueous phase was reextracted twice with ethyl acetate. The combined organic layers were dried over magnesium sulfate, filtered, and concentrated to dryness. The crude product was purified by chromatography on silica gel with ethyl acetate and ethyl acetate-methanol (9:1). Fractions containing the product were combined. After evaporation of the solvent, the residue was re-dissolved in 15 ml of ethyl acetate and 1 N solution of hydrochloric acid in diethyl ether was added. The precipitated hydrochloride salt was collected by filtration and dried to give 0.54 g of the title product.

後処理

  1. stirringThe mixture was stirred at 80° C. for 2 h
  2. customafter evaporation of dimethylformamide
  3. custompartitioned between 20 ml of ethyl acetate and 15 ml of saturated aqueous sodium chloride solution and 15 ml of water
  4. dry with materialThe combined organic layers were dried over magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness
  7. customThe crude product was purified by chromatography on silica gel with ethyl acetate and ethyl acetate-methanol (9:1)
  8. additionFractions containing the product
  9. customAfter evaporation of the solvent
  10. dissolutionthe residue was re-dissolved in 15 ml of ethyl acetate
  11. addition1 N solution of hydrochloric acid in diethyl ether was added
  12. filtrationThe precipitated hydrochloride salt was collected by filtration
  13. customdried

出典と根拠

ORDレコード
ord-1c33b3b73bab49a498f0f99f5933d74d
出典データセット
uspto-grants-2012_06
特許番号
US08202868B2

反応ノート

読み込み中…