N,N-二异丙基乙胺 → N-(5-(2,2-difluoro-6-methylbenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2,6-difluorobenzamide

HRID 874635笔记

反应方程式

HRID 874635 反应方程式
[F:1][C:2]1[CH:10]=[CH:9][CH:8]=[C:7]([F:11])[C:3]=1[C:4](Cl)=[O:5].[F:12][C:13]1([F:30])[O:17][C:16]2[CH:18]=[C:19]([CH3:29])[C:20]([C:22]3[N:23]=[CH:24][C:25]([NH2:28])=[N:26][CH:27]=3)=[CH:21][C:15]=2[O:14]1.CCN(C(C)C)C(C)C>ClCCl.O1CCCC1.CO.[OH-].[Na+]>[F:30][C:13]1([F:12])[O:17][C:16]2[CH:18]=[C:19]([CH3:29])[C:20]([C:22]3[N:23]=[CH:24][C:25]([NH:28][C:4](=[O:5])[C:3]4[C:2]([F:1])=[CH:10][CH:9]=[CH:8][C:7]=4[F:11])=[N:26][CH:27]=3)=[CH:21][C:15]=2[O:14]1

参与物

8

反应物 3

HCID 81531N,N-二异丙基乙胺HCID 874382,6-二氟苯甲酰氯HCID 584870495-(2,2-Difluoro-6-methylbenzo[d][1,3]dioxol-5-yl)pyrazin-2-amine

产物 1

HCID 58487084N-(5-(2,2-difluoro-6-methylbenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2,6-difluorobenzamide收率 65.1%

试剂、催化剂与溶剂 4

HCID 887Methanol溶剂HCID 6344二氯甲烷溶剂HCID 8028四氢呋喃溶剂HCID 14798氢氧化钠溶剂

反应条件

温度
60 °C

实验过程

Under an atmosphere of argon, 2,6-difluorobenzoyl chloride (40 mg, 0.2 mmol) was added to a stirred solution of 9 (30 mg, 0.1 mmol) and Hünig's base (120 μL, 88 mg, 0.7 mmol) in dichloromethane (1.0 mL) at room temperature. The reaction was stirred for 0.5 h. The solution was diluted with tetrahydrofuran (0.9 mL), methanol (0.6 mL) and 2 M sodium hydroxide solution (0.2 mL). The mixture was stirred and heated to 60° C. for 10 min then cooled to room temperature, extracted with dichloromethane (3×5 mL), dried with sodium sulfate and concentrated under reduced pressure. Flash chromatography (ISCO system, silica, 0-20% ethyl acetate in hexane) provided 10 (26.4 mg, 58%) as a crystalline solid: LRESIMS m/z 406.1 [M+H]+, calcd. for C19H12F4N3O3 406.1.

后处理

  1. stirringThe mixture was stirred
  2. temperaturethen cooled to room temperature
  3. extractionextracted with dichloromethane (3×5 mL)
  4. dry with materialdried with sodium sulfate
  5. concentrationconcentrated under reduced pressure

来源与证据

ORD记录
ord-d798c3e934fe4bc3a7768a5c04a0ff88
来源数据集
uspto-grants-2015_03
专利号
US08980629B2

反应笔记

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