Ammonia → 4-[3-(2-Chloro-ethyl)-cinnolin-7-yl]-benzonitrile

HRID 273248

反応式

HRID 273248 の反応式
Br[C:2]1[CH:11]=[C:10]2[C:5]([C:6](Cl)=[C:7]([CH2:12][CH2:13][Cl:14])[N:8]=[N:9]2)=[CH:4][CH:3]=1.[C:16]([C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1)#[N:17].C([O-])([O-])=O.[Na+].[Na+].N>C(O)(C)C.C1(C)C=CC=CC=1.O.Cl[Pd](Cl)([P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1)[P](C1C=CC=CC=1)(C1C=CC=CC=1)C1C=CC=CC=1>[Cl:14][CH2:13][CH2:12][C:7]1[N:8]=[N:9][C:10]2[C:5]([CH:6]=1)=[CH:4][CH:3]=[C:2]([C:21]1[CH:22]=[CH:23][C:18]([C:16]#[N:17])=[CH:19][CH:20]=1)[CH:11]=2

参加物

8

反応物 4

HCID 222AmmoniaHCID 10340Sodium CarbonateHCID 27343264-Cyanophenylboronic acidHCID 671047587-Bromo-4-chloro-3-(2-chloro-ethyl)-cinnoline

生成物 1

HCID 671047734-[3-(2-Chloro-ethyl)-cinnolin-7-yl]-benzonitrile収率 50%

試薬・触媒・溶媒 3

HCID 178418476HCID 178418476、化合物触媒HCID 962Water溶媒HCID 21881414Toluene isopropyl alcohol溶媒

反応条件

温度
90 °C

実験手順

A mixture of the product from Example 169C (0.095 g, 0.312 mmol), 4-cyanophenylboronic acid (0.046 g, 0.343 mmol), Pd(PPh3)2Cl2 (0.011 g, 0.016 mmol), and 1 M Na2CO3 (0.778 mL, 0.778 mmol) in de-gassed isopropanol/toluene (5 mL, 1:1) was heated to 90° C. under a dry nitrogen atmosphere for 24 hours. After cooling, the reaction mixture was diluted with 20 mL water, extracted twice with 25 mL dichloromethane, and concentrated under reduced pressure. The crude material was purified by column chromatography (1000% dichloromethane to 99:1 dichloromethane/methanol) to afford the product in 50% yield as a brown-orange solid. 1H NMR (CDCl3, 300 MHz) δ 8.76 (d, J=3 Hz, 1H), 8.02 (dd, J=3, 9 Hz, 1H), 7.96 (d, J=9 Hz, 1H), 7.87 (q, J=9 Hz, 4H), 7.80 (s, 1H), 4.14 (t, J=6 Hz, 2H), 3.69 (t, J=6 Hz, 2H). MS (DCl—NH3) [M−Cl]+ at 258, [M+H]+ at 294.

後処理

  1. temperatureAfter cooling
  2. extractionextracted twice with 25 mL dichloromethane
  3. concentrationconcentrated under reduced pressure
  4. customThe crude material was purified by column chromatography (1000% dichloromethane to 99:1 dichloromethane/methanol)
  5. customto afford the product in 50% yield as a brown-orange solid

出典と根拠

ORDレコード
ord-b7f11058898841cd9eae48c1291f3136
出典データセット
uspto-grants-2008_11
特許番号
US07456196B2

関連ノート

読み込み中…