Potassium Phosphate, Tribasic → 1-(5-(6-Cyanopyridin-3-yl)-6-fluorobenzo[d]thiazol-2-yl)-3-ethylurea

HRID 2068692Notes

Reaction equation

HRID 2068692 reaction equation
Br[C:2]1[C:3]([F:17])=[CH:4][C:5]2[S:9][C:8]([NH:10][C:11]([NH:13][CH2:14][CH3:15])=[O:12])=[N:7][C:6]=2[CH:16]=1.CC1(C)C(C)(C)OB([C:26]2[CH:27]=[CH:28][C:29]([C:32]#[N:33])=[N:30][CH:31]=2)O1.[O-]P([O-])([O-])=O.[K+].[K+].[K+]>CN(C=O)C.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>[C:32]([C:29]1[N:30]=[CH:31][C:26]([C:2]2[C:3]([F:17])=[CH:4][C:5]3[S:9][C:8]([NH:10][C:11]([NH:13][CH2:14][CH3:15])=[O:12])=[N:7][C:6]=3[CH:16]=2)=[CH:27][CH:28]=1)#[N:33]

Participants

6

Reactant 3

HCID 62657Potassium Phosphate, TribasicHCID 164141882-Cyanopyridine-5-boronic acid pinacol esterHCID 596030721-(5-Bromo-6-fluoro-benzothiazol-2-yl)-3-ethyl-urea

Product 1

HCID 866481461-(5-(6-Cyanopyridin-3-yl)-6-fluorobenzo[d]thiazol-2-yl)-3-ethylureaYield 71%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 21962138N,N-Dimethylformamide--water (1/1)Solvent

Conditions

Temperature
100 °C

Procedure

A solution of 1-(5-bromo-6-fluoro-benzothiazol-2-yl)-3-ethyl-urea (0.10 g, 0.31 mmol), 5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)picolinonitrile (0.144 g, 0.63 mmol) and K3PO4 (0.133 g, 0.63 mmol) in DMF-H2O (5.0 mL, 4:1) was degassed by flushing with nitrogen for 15 min. Dichlorobis(triphenylphosphine)-palladium(II) (0.022 g, 0.03 mmol) was then added to the reaction mixture followed by degassing with nitrogen for another 15 min. The resulting reaction mixture was then heated to 100° C. for 2 h. After the completion of the reaction (TLC monitoring), the reaction mixture was cooled to room temperature and poured onto ice-cold water followed by extraction with EtOAc (2×50 mL). The combined organics was washed with brine, dried (Na2SO4), filtered and concentrated under reduced pressure. The crude was then purified over silica gel (100-200 M, 2.50% MeOH-DCM) to obtain the desired product (0.075 g, 71%). 1H-NMR (400 MHz, DMSO-d6): δ 1.09 (t, J=7.20 Hz, 3H), 3.20 (m, 2H), 6.71 (br s, 1H), 7.90 (d, J=6.80 Hz, 1H), 8.03 (d, J=10.80 Hz, 1H), 8.15 (m, 1H), 8.31 (m, 1H), 9.0 (s, 1H) and 10.90 (br s, 1H). MS: 340.06 (M−H)+.

Workup

  1. customby flushing with nitrogen for 15 min
  2. customby degassing with nitrogen for another 15 min
  3. customThe resulting reaction mixture
  4. customAfter the completion of the reaction (TLC monitoring)
  5. temperaturethe reaction mixture was cooled to room temperature
  6. additionpoured onto ice-cold water
  7. extractionfollowed by extraction with EtOAc (2×50 mL)
  8. washThe combined organics was washed with brine
  9. dry with materialdried (Na2SO4)
  10. filtrationfiltered
  11. concentrationconcentrated under reduced pressure
  12. customThe crude was then purified over silica gel (100-200 M, 2.50% MeOH-DCM)

Sources & evidence

ORD record
ord-ffc2179d802149b5bbd31b6d38ecda47
Source dataset
uspto-grants-2012_10
Patent number
US08299065B2

Reaction notes

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