1,10-Phenanthroline → tert-Butyl 4-(isoquinolin-5-yl)-3-oxopiperazine-1-carboxylate

HRID 63828

反応式

HRID 63828 の反応式
Br[C:2]1[CH:11]=[CH:10][CH:9]=[C:8]2[C:3]=1[CH:4]=[CH:5][N:6]=[CH:7]2.[O:12]=[C:13]1[NH:18][CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:25])([CH3:24])[CH3:23])=[O:20])[CH2:14]1.N1C2C(=CC=C3C=2N=CC=C3)C=CC=1.C([O-])([O-])=O.[K+].[K+]>[Cu]I.CS(C)=O>[CH:7]1[C:8]2[C:3](=[C:2]([N:18]3[CH2:17][CH2:16][N:15]([C:19]([O:21][C:22]([CH3:24])([CH3:23])[CH3:25])=[O:20])[CH2:14][C:13]3=[O:12])[CH:11]=[CH:10][CH:9]=2)[CH:4]=[CH:5][N:6]=1

参加物

7

反応物 4

HCID 13181,10-PhenanthrolineHCID 11430Potassium CarbonateHCID 7364875-BromoisoquinolineHCID 3157178Tert-butyl 3-oxopiperazine-1-carboxylate

生成物 1

HCID 131732696tert-Butyl 4-(isoquinolin-5-yl)-3-oxopiperazine-1-carboxylate収率 54%

試薬・触媒・溶媒 2

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)触媒HCID 679Dimethyl Sulfoxide溶媒

反応条件

温度
130 °C

実験手順

To 5-bromoisoquinoline (0.3 g, 1.442 mmol) and tert-butyl 3-oxopiperazine-1-carboxylate (0.289 g, 1.442 mmol) was added DMSO (4 mL), 1,10-phenanthroline (0.026 g, 0.144 mmol) and K2CO3 (0.498 g, 3.60 mmol). The mixture was degassed for 10 min and then was added CuI (0.055 g, 0.288 mmol). The reaction was heated in a sealed tube in oil bath at 130° C. After 24 h, the reaction was incomplete. After cooling and degassing with argon, more CuI was added and heating was repeated. After 24 h, the reaction was quenched with dilute NH4OH (15 mL) and extracted with EtOAc (3×30 mL). The combined organic layers were washed with brine (15 mL) and dried (MgSO4). The crude product was purified by normal phase chromatography followed by HPLC. After partitioning with saturated NaHCO3 (15 mL) and EtOAc (50 mL), organic layer was washed with brine and dried (MgSO4) to afford 0.157 g (54%) of Intermediate 21A as a white solid. MS (ESI) m/z: 328 (M+H)+.

後処理

  1. customThe mixture was degassed for 10 min
  2. temperatureAfter cooling
  3. customdegassing with argon, more CuI
  4. additionwas added
  5. temperatureheating
  6. waitAfter 24 h
  7. customthe reaction was quenched with dilute NH4OH (15 mL)
  8. extractionextracted with EtOAc (3×30 mL)
  9. washThe combined organic layers were washed with brine (15 mL)
  10. dry with materialdried (MgSO4)
  11. customThe crude product was purified by normal phase chromatography
  12. customAfter partitioning with saturated NaHCO3 (15 mL) and EtOAc (50 mL), organic layer
  13. washwas washed with brine
  14. dry with materialdried (MgSO4)

出典と根拠

ORDレコード
ord-f0027b1bae5f4804afe82ce71258eba7
出典データセット
uspto-grants-2016_09
特許番号
US09447110B2

関連ノート

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