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Water → 3-Chloro-5-fluoro-2-thiazolo[5,4-c]pyridin-2-yl-benzonitrile

HRID 2366324
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HRID 2366324 반응식
[N:1]1[C:9]2[CH:8]=[CH:7][N:6]=[CH:5][C:4]=2[S:3][CH:2]=1.Br[C:11]1[C:18]([Cl:19])=[CH:17][C:16]([F:20])=[CH:15][C:12]=1[C:13]#[N:14].C(=O)([O-])[O-].[Cs+].[Cs+].O>CN(C)C=O.C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1.[Cu]I>[Cl:19][C:18]1[C:11]([C:2]2[S:3][C:4]3[CH:5]=[N:6][CH:7]=[CH:8][C:9]=3[N:1]=2)=[C:12]([CH:15]=[C:16]([F:20])[CH:17]=1)[C:13]#[N:14]
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참가 물질

8

반응물 4

HCID 962WaterHCID 10796Cesium carbonateHCID 14666228Thiazolo[5,4-c]pyridineHCID 668014342-Bromo-3-chloro-5-fluorobenzonitrile

생성물 1

HCID 668014643-Chloro-5-fluoro-2-thiazolo[5,4-c]pyridin-2-yl-benzonitrile수율 20.7%

시약·촉매·용매 3

HCID 24350
Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)
촉매
HCID 178418397HCID 178418397, 화합물촉매
HCID 6228Dimethylformamide용매

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온도
150 °C

실험 절차

A mixture of thiazolo[5,4-c]pyridine (0.5 g, 3.67 mmol), 2-bromo-3-chloro-5-fluorobenzonitrile (1.3 g, 5.5 mmol), Pd(PPh3)4 (0.42 g, 0.36 mmol), copper(I) iodide (70 mg, 0.37 mmol) and cesium carbonate (3.9 g, 12 mmol) in dimethylformamide (15 mL) was heated at 150° C. in a microwave reactor for 5 minutes. The cooled mixture was poured into water and extracted twice with ethyl acetate. The combined organic extracts were washed with water, dried (Na2SO4), filtered and concentrated in vacuo. The crude product was purified by chromatography on silica (10% diethylether in DCM) to yield a pale solid (0.22 g). The reaction was repeated on the same scale, and the combined product from both reactions was purified by chromatography on silica (5% diethylether in DCM) to give the title compound as an off-white solid (0.30 g, 14%). 1H NMR (300 MHz, CDCl3): δ 9.35 (s, 1H), 8.78 (d, J=6.2 Hz, 1H), 8.10 (d, J=6.2 Hz, 1H), 7.58 (dd, J=7.8, 2.5 Hz, 1H), 7.53 (dd, J=7.4, 2.5 Hz, 1H). LCMS (Method E): RT=2.78, m/z: 290 [M+H+].

후처리

  1. extractionextracted twice with ethyl acetate
  2. washThe combined organic extracts were washed with water
  3. dry with materialdried (Na2SO4)
  4. filtrationfiltered
  5. concentrationconcentrated in vacuo
  6. customThe crude product was purified by chromatography on silica (10% diethylether in DCM)

출처 및 근거

ORD 기록
ord-85e6a1f0a541475395393b998c924eff
출처 데이터셋
uspto-grants-2014_04
DOI
10.6084/m9.figshare.5104873.v1
특허 번호
US08697708B2

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