Sodium Carbonate → 1-[5-(7-Pyridin-4-yl-imidazo[1,2-a]pyridin-3-yl)-pyridin-2-yl]-3-(m-trifluoromethyl-phenyl)-urea

HRID 1446748Notes

Reaction equation

HRID 1446748 reaction equation
Br[C:2]1[CH:3]=[CH:4][C:5]([NH:8][C:9]([NH:11][C:12]2[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=2)=[O:10])=[N:6][CH:7]=1.B1(B2OC(C)(C)C(C)(C)O2)OC(C)(C)C(C)(C)O1.C1(P(C2CCCCC2)C2CCCCC2)CCCCC1.C([O-])(=O)C.[K+].I[C:65]1[N:69]2[CH:70]=[CH:71][C:72]([C:74]3[CH:79]=[CH:78][N:77]=[CH:76][CH:75]=3)=[CH:73][C:68]2=[N:67][CH:66]=1.C(=O)([O-])[O-].[Na+].[Na+]>O1CCOCC1>[N:77]1[CH:76]=[CH:75][C:74]([C:72]2[CH:71]=[CH:70][N:69]3[C:65]([C:2]4[CH:3]=[CH:4][C:5]([NH:8][C:9]([NH:11][C:12]5[CH:17]=[CH:16][CH:15]=[C:14]([C:18]([F:21])([F:20])[F:19])[CH:13]=5)=[O:10])=[N:6][CH:7]=4)=[CH:66][N:67]=[C:68]3[CH:73]=2)=[CH:79][CH:78]=1

Participants

8

Reactant 6

HCID 10340Sodium CarbonateHCID 75806TricyclohexylphosphineHCID 517044Potassium AcetateHCID 2733548Bis(pinacolato)diboraneHCID 606503781-(5-Bromopyridin-2-yl)-3-(3-(trifluoromethyl)phenyl)ureaHCID 685421433-Iodo-7-pyridin-4-yl-imidazo[1,2-a]pyridine

Product 1

HCID 578634571-[5-(7-Pyridin-4-yl-imidazo[1,2-a]pyridin-3-yl)-pyridin-2-yl]-3-(m-trifluoromethyl-phenyl)-ureaYield 69%

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
80 °C

Procedure

To a solution of 1-(5-bromopyridin-2-yl)-3-(m-trifluoromethylphenyl)-urea (0.520 g, 1.44 mmol, 1.0 eq.) in dioxane (12 mL), add bis(pinacolato)diboron (0.410 g, 1.59 mmol, 1.1 eq.), tricyclohexylphosphine (0.048 g, 12 mol %), potassium acetate (0.211 g, 1.5 eq.), and tris(dibenzylidineacetone)dipalladium (0) (0.066 g, 5 mmol %). Deoxygenate the reaction mixture and stir under nitrogen at 80° C. for approximately 16 h and cool to room temperature. Add 3-iodo-7-pyridin-4-yl-imidazo[1,2-a]pyridine (0.460 g, 1.44 mmol, 1.0 eq.), sodium carbonate solution (2 M, 3 mL) and tetralis(triphenylphosphine)palladium (0) (0.083 g, 5 mmol %). Deoxygenate the reaction mixture and stir at 80° C. for 6 hours, cool, then purify on a SCX cartridge (Varian) as in Example 115. Concentrate SCX-eluted materials and purify via silica gel flash chromatography employing a 0-4% gradient of methanol in dichloromethane to afford 0.450 g (0.99 mmol, 69%) of the title compound. MS (ES), m/z 475 (M+1).

Workup

  1. customDeoxygenate the reaction mixture
  2. temperaturecool to room temperature
  3. customDeoxygenate the reaction mixture
  4. stirringstir at 80° C. for 6 hours
  5. temperaturecool
  6. custompurify on a SCX cartridge (Varian) as in Example 115
  7. customConcentrate SCX-eluted materials and purify via silica gel flash chromatography

Sources & evidence

ORD record
ord-c4003c63fefa4a6fbb6e99ddd4b5e457
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

Loading…