Potassium Phosphate, Tribasic → 1-Ethyl-3-[7-(2-fluoro-phenyl)-5-pyridin-3-yl-benzothiazol-2-yl]-urea

HRID 1010649Notes

Reaction equation

HRID 1010649 reaction equation
Br[C:2]1[C:10]2[S:9][C:8]([NH:11][C:12]([NH:14][CH2:15][CH3:16])=[O:13])=[N:7][C:6]=2[CH:5]=[C:4]([C:17]2[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=2)[CH:3]=1.[F:23][C:24]1[CH:29]=[CH:28][CH:27]=[CH:26][C:25]=1B(O)O.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>O1CCOCC1.CO>[CH2:15]([NH:14][C:12]([NH:11][C:8]1[S:9][C:10]2[C:2]([C:25]3[CH:26]=[CH:27][CH:28]=[CH:29][C:24]=3[F:23])=[CH:3][C:4]([C:17]3[CH:18]=[N:19][CH:20]=[CH:21][CH:22]=3)=[CH:5][C:6]=2[N:7]=1)=[O:13])[CH3:16]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 27343542-Fluorophenylboronic acidHCID 248642171-(7-Bromo-5-pyridin-3-yl-benzothiazol-2-yl)-3-ethyl-urea

Product 1

HCID 578136721-Ethyl-3-[7-(2-fluoro-phenyl)-5-pyridin-3-yl-benzothiazol-2-yl]-ureaYield 23%

Reagents, catalysts & solvents 2

HCID 887MethanolSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

A stirred mixture of 1-(7-Bromo-5-pyridin-3-yl-benzothiazol-2-yl)-3-ethyl-urea (50 mg, 0.133 mmol), 2-fluorobenzeneboronic acid (19 mg, 0.139 mmol), powdered potassium phosphate tribasic (34 mg, 0.160 mmol) and 1,1′-bis(diphenylphosphino)ferrocene palladium(II) chloride complex (16 mg, 0.01995 mmol) in anhydrous 1,4-dioxane (1 ml) and anhydrous methanol (2 ml) was purged with nitrogen for 5 min and heated in a sealed vessel for 16 h at 80° C. After cooling to ambient temperature, the mixture was filtered through kieselguhr. The kieselguhr was thoroughly washed with methanol and the combined filtrates evaporated to dryness in vacuo to give the crude 1-Ethyl-3-[7-(2-fluoro-phenyl)-5-pyridin-3-yl-benzothiazol-2-yl]-urea which was purified by “flash” silica chromatography eluting with 0 to 30% methanol in ethyl acetate. 12 mg of a pale-brown solid was obtained.

Workup

  1. customwas purged with nitrogen for 5 min
  2. temperatureAfter cooling to ambient temperature
  3. filtrationthe mixture was filtered through kieselguhr
  4. washThe kieselguhr was thoroughly washed with methanol
  5. customthe combined filtrates evaporated to dryness in vacuo
  6. customto give the crude 1-Ethyl-3-[7-(2-fluoro-phenyl)-5-pyridin-3-yl-benzothiazol-2-yl]-urea which
  7. customwas purified by “flash” silica chromatography
  8. washeluting with 0 to 30% methanol in ethyl acetate

Sources & evidence

ORD record
ord-f067975e8ff246aeb6d3c302ca121459
Source dataset
uspto-grants-2011_07
Patent number
US07977340B2

Reaction notes

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