Water → HCID 66619680, compound

HRID 415654Notes

Reaction equation

HRID 415654 reaction equation
Br[C:2]1[N:7]=[C:6]2[S:8][C:9]([CH2:11][O:12][C:13]3[C:14]([F:23])=[C:15]([C:19]([F:22])=[CH:20][CH:21]=3)[C:16]([NH2:18])=[O:17])=[N:10][C:5]2=[CH:4][CH:3]=1.[CH3:24][N:25]1[CH:29]=[CH:28][N:27]=[C:26]1[Sn](CCCC)(CCCC)CCCC.O>CN(C=O)C.[Pd].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1>[F:23][C:14]1[C:13]([O:12][CH2:11][C:9]2[S:8][C:6]3[C:5]([N:10]=2)=[CH:4][CH:3]=[C:2]([C:26]2[N:25]([CH3:24])[CH:29]=[CH:28][N:27]=2)[N:7]=3)=[CH:21][CH:20]=[C:19]([F:22])[C:15]=1[C:16]([NH2:18])=[O:17]

Participants

6

Reactant 3

HCID 962WaterHCID 27632521-Methyl-2-(tributylstannyl)-1H-imidazoleHCID 866432773-(5-Bromo-thiazolo[5,4-b]pyridin-2-ylmethoxy)-2,6-difluoro-benzamide

Product 1

HCID 66619680HCID 66619680, compound

Reagents, catalysts & solvents 2

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
120 °C

Procedure

To a solution of 3-(5-bromo-thiazolo[5,4-b]pyridin-2-ylmethoxy)-2,6-difluoro-benzamide (0.10 g, 0.24 mmol) in 5 ml of anhydrous DMF was added 1-methyl-2-tributylstannanyl-1H-imidazole (0.120 g, 0.32 mmol) and degassed the reaction mixture for the 10 minutes. Tetrakis(triphenylphosphine) palladium (0) (0.004 g, 0.0037 mmol) was then added and the reaction mixture was heated at 120° C. for 12 h under the nitrogen atmosphere. The reaction mixture was then cooled to room temperature, added water (25 mL) and extracted the compound with ethyl acetate. The combined organic layers were dried over anhydrous Na2SO4, and evaporated to dryness under reduced pressure. The compound was purified by column chromatography on silica (230-400 M) using ethyl acetate/hexane (40:60) as the eluent to provide the title compound as brick red solid (0.020 g, 20%). 1H NMR (DMSO-d6, 400 MHz): δ 3.14 (s, 3H), 5.67 (s, 2H), 7.07 (m, 1H), 7.28-7.37 (m, 2H), 7.87 (m, 2H), 8.28 (s, 1H), 8.53 (s, 1H) and 8.75 (br s, 1H). MS ES+ (402.22), HPLC (method I) Rt=12.05 min.

Workup

  1. customdegassed the reaction mixture for the 10 minutes
  2. temperatureThe reaction mixture was then cooled to room temperature
  3. extractionextracted the compound with ethyl acetate
  4. dry with materialThe combined organic layers were dried over anhydrous Na2SO4
  5. customevaporated to dryness under reduced pressure
  6. customThe compound was purified by column chromatography on silica (230-400 M)

Sources & evidence

ORD record
ord-470be71c8772454a823a2bc9235cefa9
Source dataset
uspto-grants-2012_01
Patent number
US08088791B2

Reaction notes

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