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

HRID 273248

반응식

HRID 273248 반응식
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

참가 물질

8

반응물 4

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

생성물 1

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

시약·촉매·용매 3

HCID 178418476HCID 178418476, 화합물촉매HCID 962Water용매HCID 21881414Toluene isopropyl alcohol용매

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온도
90 °C

실험 절차

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.

후처리

  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

출처 및 근거

ORD 기록
ord-b7f11058898841cd9eae48c1291f3136
출처 데이터셋
uspto-grants-2008_11
특허 번호
US07456196B2

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