Triethylamine → 6-(3-Ethylureido)-4-(4-(1-methyl-1h-pyrazol-4-yl)thiazol-2-yl)pyridin-3-ylboronic acid

HRID 1047178Notes

Reaction equation

HRID 1047178 reaction equation
Br[C:2]1[C:3]([C:14]2[S:15][CH:16]=[C:17]([C:19]3[CH:20]=[N:21][N:22]([CH3:24])[CH:23]=3)[N:18]=2)=[CH:4][C:5]([NH:8][C:9]([NH:11][CH2:12][CH3:13])=[O:10])=[N:6][CH:7]=1.CC1(C)C(C)(C)[O:29][B:28](B2OC(C)(C)C(C)(C)O2)[O:27]1.C(N(CC)CC)C.C([O-])(=O)C.[K+]>O1CCOCC1.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>[CH2:12]([NH:11][C:9](=[O:10])[NH:8][C:5]1[N:6]=[CH:7][C:2]([B:28]([OH:29])[OH:27])=[C:3]([C:14]2[S:15][CH:16]=[C:17]([C:19]3[CH:20]=[N:21][N:22]([CH3:24])[CH:23]=3)[N:18]=2)[CH:4]=1)[CH3:13]

Participants

7

Reactant 4

HCID 8471TriethylamineHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 670574731-(5-bromo-4-(4-(1-methyl-1H-pyrazol-4-yl)thiazol-2-yl)pyridin-2-yl)-3-ethylurea2×

Product 1

HCID 672880116-(3-Ethylureido)-4-(4-(1-methyl-1h-pyrazol-4-yl)thiazol-2-yl)pyridin-3-ylboronic acidYield 34.2%

Reagents, catalysts & solvents 2

HCID 178418476HCID 178418476, compoundCatalystHCID 312751,4-DioxaneSolvent

Conditions

Temperature
40 °C

Procedure

In a 100 mL flask 1-(5-bromo-4-(4-(1-methyl-1H-pyrazol-4-yl)thiazol-2-yl)pyridin-2-yl)-3-ethylurea (Intermediate 97, 1.28 g, 3.14 mmol) was dissolved in 1,4-dioxane (15 mL) at 40° C. and degassed with argon. Bis(triphenylphosphine)palladium chloride (0.221 g, 0.31 mmol) was added and allow it to react for 10 minutes while heating at 40° C. 4,4,4′,4′,5,5,5′,5′-octamethyl-2,2′-bi(1,3,2-dioxaborolane) (2.394 g, 9.43 mmol) was added and stirred for 10 minutes while heating at 100° C. Triethylamine (1.314 mL, 9.43 mmol) and potassium acetate (0.925 g, 9.43 mmol) were added and the solution was heated at 100° C. for 15 h. The reaction mixture was cooled to room temperature, filtered through a pad of Celite and partitioned between water and ethyl acetate. The layers were separated and the aqueous layer was back extracted three times with ethyl acetate. The organic layers were combined and washed with water and brine, then dried over sodium sulfate and concentrated under reduced pressure, and purified by column chromatography (Silica gel, 0-10% MeOH in CH2Cl2). Isolation gave 400 mg of the title compound as an off-white solid.

Workup

  1. customdegassed with argon
  2. customto react for 10 minutes
  3. temperaturewhile heating at 100° C
  4. temperaturethe solution was heated at 100° C. for 15 h
  5. temperatureThe reaction mixture was cooled to room temperature
  6. filtrationfiltered through a pad of Celite
  7. custompartitioned between water and ethyl acetate
  8. customThe layers were separated
  9. extractionthe aqueous layer was back extracted three times with ethyl acetate
  10. washwashed with water and brine
  11. dry with materialdried over sodium sulfate
  12. concentrationconcentrated under reduced pressure
  13. custompurified by column chromatography (Silica gel, 0-10% MeOH in CH2Cl2)

Sources & evidence

ORD record
ord-68cc66791855410eabfe4ab89f87f190
Source dataset
uspto-grants-2013_10
Patent number
US08569484B2

Reaction notes

Loading…