Diisopropylethylamine → N-(5-(2,2-difluoro-6-methylbenzo[d][1,3]dioxol-5-yl)pyrazin-2-yl)-2,6-difluorobenzamide

HRID 1036108ノート

反応式

HRID 1036108 の反応式
[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

参加物

8

反応物 3

HCID 81531DiisopropylethylamineHCID 874382,6-Difluorobenzoyl chlorideHCID 584870495-(2,2-Difluoro-6-methylbenzo[d][1,3]dioxol-5-yl)pyrazin-2-amine

生成物 1

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

試薬・触媒・溶媒 4

HCID 887Methanol溶媒HCID 6344Dichloromethane溶媒HCID 8028Tetrahydrofuran溶媒HCID 14798Sodium Hydroxide溶媒

反応条件

温度
60 °C

実験手順

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.

後処理

  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

出典と根拠

ORDレコード
ord-8fe8ceeea0bc4abd89a67f27ee045f4e
出典データセット
uspto-grants-2013_10
特許番号
US08546403B2

反応ノート

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