N,N'-二甲基乙二胺 → 1-(4-(3,4-dichlorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)pyridin-2(1H)-one

HRID 576106

反应方程式

HRID 576106 反应方程式
Br[C:2]1[CH:11]=[C:10]2[C:5]([CH:6]([C:13]3[CH:18]=[CH:17][C:16]([Cl:19])=[C:15]([Cl:20])[CH:14]=3)[CH2:7][N:8]([CH3:12])[CH2:9]2)=[CH:4][CH:3]=1.BrCC(C1C=CC(Cl)=C(Cl)C=1)=O.BrC1C=C(CNC)C=CC=1.[N:43]1[CH:48]=[CH:47][CH:46]=[CH:45][C:44]=1[OH:49].CNCCNC.P([O-])([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.[Cu]I>[Cl:20][C:15]1[CH:14]=[C:13]([CH:6]2[C:5]3[C:10](=[CH:11][C:2]([N:43]4[CH:48]=[CH:47][CH:46]=[CH:45][C:44]4=[O:49])=[CH:3][CH:4]=3)[CH2:9][N:8]([CH3:12])[CH2:7]2)[CH:18]=[CH:17][C:16]=1[Cl:19]

参与物

9

反应物 6

HCID 8070N,N'-二甲基乙二胺HCID 62657POTASSIUM DIPHOSPHATEHCID 244751α-溴代-3,4-二氯苯乙酮HCID 457588N-甲基-3-溴苄胺HCID 667882077-Bromo-4-(3,4-dichlorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinolineHCID 178516071HCID 178516071，化合物

产物 1

HCID 667885251-(4-(3,4-dichlorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)pyridin-2(1H)-one收率 7.1%

试剂、催化剂与溶剂 2

HCID 24350碘化亚铜催化剂HCID 312751,4-二氧六环溶剂

反应条件

温度
110 °C

实验过程

To a mixture of 7-bromo-4-(3,4-dichlorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinoline (500 mg, 1.35 mmol) which was prepared following similar method described in Steps A to C of Example 1 starting from 2-bromo-1-(3,4-dichlorophenyl)ethanone and 1-(3-bromophenyl)-N-methylmethanamine, pyridin-2-ol (154 mg, 1.62 mmol), N,N′-dimethylethylene diamine (58 μl, 0.54 mmol), and potassium phosphate (572 mg, 2.69 mmol) in 1,4-dioxane (5 mL) was added copper(1) iodide (51 mg, 0.27 mmol). The mixture was degassed with argon and then heated to 110° C. for 17 hours. The reaction mixture was diluted with water (20 mL) and extracted with methylene chloride (2×25 mL). The combined organics were dried over sodium sulfate, filtered, and concentrated in vacuo. The residue was partially purified by column chromatography (methylene chloride to 90:9:1 methylene chloride/methanol/ammonium hydroxide) to give 1-(4-(3,4-dichlorophenyl)-2-methyl-1,2,3,4-tetrahydroisoquinolin-7-yl)pyridin-2(1H)-one (37 mg, 7%): ESI MS m/z 385 [M+H]+.

后处理

  1. customwas prepared
  2. customThe mixture was degassed with argon
  3. additionThe reaction mixture was diluted with water (20 mL)
  4. extractionextracted with methylene chloride (2×25 mL)
  5. dry with materialThe combined organics were dried over sodium sulfate
  6. filtrationfiltered
  7. concentrationconcentrated in vacuo
  8. customThe residue was partially purified by column chromatography (methylene chloride to 90:9:1 methylene chloride/methanol/ammonium hydroxide)

来源与证据

ORD记录
ord-0e5259f31ac845dbb4b124b976f9a35e
来源数据集
uspto-grants-2015_05
专利号
US09034899B2

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