三乙胺 → 4-Cyano-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-N,N,5-trimethyl-6-vinyl-1,3-benzoxazole-2-carboxamide

HRID 17469笔记

反应方程式

HRID 17469 反应方程式
[C:1]([C:3]1[C:8]2[N:9]=[C:10]([C:12]([N:14]([CH3:16])[CH3:15])=[O:13])[O:11][C:7]=2[C:6](F)=[C:5]([CH:18]=[CH2:19])[C:4]=1[CH3:20])#[N:2].C(N(CC)CC)C.[CH3:28][N:29]([CH3:35])[C@H:30]1[CH2:34][CH2:33][NH:32][CH2:31]1.C(=O)([O-])O.[Na+]>CS(C)=O.C(OCC)(=O)C>[C:1]([C:3]1[C:8]2[N:9]=[C:10]([C:12]([N:14]([CH3:16])[CH3:15])=[O:13])[O:11][C:7]=2[C:6]([N:32]2[CH2:33][CH2:34][C@H:30]([N:29]([CH3:35])[CH3:28])[CH2:31]2)=[C:5]([CH:18]=[CH2:19])[C:4]=1[CH3:20])#[N:2]

参与物

7

反应物 4

HCID 8471三乙胺HCID 516892碳酸氢钠HCID 7019156(3S)-(-)-3-(二甲氨基)吡咯烷HCID 685862624-Cyano-7-fluoro-N,N,5-trimethyl-6-vinyl-1,3-benzoxazole-2-carboxamide

产物 1

HCID 685849044-Cyano-7-[(3S)-3-(dimethylamino)pyrrolidin-1-yl]-N,N,5-trimethyl-6-vinyl-1,3-benzoxazole-2-carboxamide收率 70.3%

试剂、催化剂与溶剂 2

HCID 679二甲基亚砜溶剂2 次HCID 8857乙酸乙酯溶剂

实验过程

4-Cyano-7-fluoro-N,N,5-trimethyl-6-vinyl-1,3-benzoxazole-2-carboxamide (I-185) (130 mg, 0.48 mmol) was dissolved in dimethyl sulfoxide (8 ml), then at room temperature, triethylamine (100 μl, 0.48 mmol) was added. The solution was gradually heated from room temperature up to 150° C. under nitrogen atmosphere, a solution of (3S)-3-(dimethylamino)pyrrolidine (79 μl, 0.62 mmol) dissolved in dimethyl sulfoxide (1 ml) was added all at a time. The solution was stirred at the same temperature for 1.25 hours, and the cooled to room temperature. This was fractionated with ethyl acetate and an aqueous saturated sodium hydrogencarbonate solution. The aqueous layer was further extracted twice with ethyl acetate. The organic layers were combined, washed with saturated brine, and dried over anhydrous sodium sulfate. The insoluble matter was separated by filtration, the solvent was evaporated away under reduced pressure, and the resulting residue was purified by preparative TLC (eluent, chloroform:methanol=93:7) to obtain a roughly-purified product (124 mg). This was washed with diisopropyl ether to obtain the entitled compound (87 mg, 50%) as a yellow solid.

后处理

  1. temperatureThe solution was gradually heated from room temperature up to 150° C. under nitrogen atmosphere
  2. additionwas added all at a time
  3. extractionThe aqueous layer was further extracted twice with ethyl acetate
  4. washwashed with saturated brine
  5. dry with materialdried over anhydrous sodium sulfate
  6. customThe insoluble matter was separated by filtration
  7. customthe solvent was evaporated away under reduced pressure
  8. customthe resulting residue was purified by preparative TLC (eluent, chloroform:methanol=93:7)

来源与证据

ORD记录
ord-3f371b60ffb142eaa34c722c345bd6b3
来源数据集
uspto-grants-2010_06
专利号
US07737166B2

反应笔记

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