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

HRID 2366324Notes

Reaction equation

HRID 2366324 reaction equation
[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]

Participants

8

Reactant 4

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

Product 1

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

Reagents, catalysts & solvents 3

HCID 24350Copper(1+) iodide; Copper(I) iodide; Cuprous iodide; Cuprous iodide (CuI)CatalystHCID 178418397HCID 178418397, compoundCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
150 °C

Procedure

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+].

Workup

  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)

Sources & evidence

ORD record
ord-85e6a1f0a541475395393b998c924eff
Source dataset
uspto-grants-2014_04
Patent number
US08697708B2

Reaction notes

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