(4-Aminophenyl)boronic acid hydrochloride → 4-(7-Thiazol-2-yl-imidazo[1,2-a]pyridin-3-yl)phenylamine

HRID 1446670Notes

Reaction equation

HRID 1446670 reaction equation
Br[C:2]1[N:6]2[CH:7]=[CH:8][C:9]([C:11]3[S:12][CH:13]=[CH:14][N:15]=3)=[CH:10][C:5]2=[N:4][CH:3]=1.Cl.[NH2:17][C:18]1[CH:23]=[CH:22][C:21](B(O)O)=[CH:20][CH:19]=1>O1CCOCC1.C(=O)([O-])[O-].[Na+].[Na+].C(OCC)(=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>[S:12]1[CH:13]=[CH:14][N:15]=[C:11]1[C:9]1[CH:8]=[CH:7][N:6]2[C:2]([C:21]3[CH:22]=[CH:23][C:18]([NH2:17])=[CH:19][CH:20]=3)=[CH:3][N:4]=[C:5]2[CH:10]=1

Participants

7

Reactant 2

HCID 2734614(4-Aminophenyl)boronic acid hydrochlorideHCID 685397873-Bromo-7-thiazol-2-yl-imidazo[1,2-a]pyridine

Product 1

HCID 685390914-(7-Thiazol-2-yl-imidazo[1,2-a]pyridin-3-yl)phenylamineYield 67.2%

Reagents, catalysts & solvents 4

HCID 11979704Tetrakis(triphenylphosphine)palladiumCatalystHCID 8857Ethyl AcetateSolventHCID 10340Sodium CarbonateSolventHCID 312751,4-DioxaneSolvent

Conditions

Temperature
95 °C

Procedure

Take up 3-bromo-7-thiazol-2-yl-imidazo[1,2-a]pyridine (1.07 g, 3.82 mmol) and 4-aminophenylboronic acid hydrochloride (793 mg, 4.58 mmol, 1.2 eq) in 15 mL of dioxane and 7 mL of 2 N aqueous sodium carbonate, then deoxygenate with vacuum/nitrogen bubbling as described above. Add tetrakis (triphenylphosphine) palladium (0) (221 mg, 0.19 1 mmol, 0.05 eq), fit the reaction flask with a reflux condenser and heat the mixture to 95° C. with stirring under nitrogen for approximately 16 hours. Cool the dark brown reaction mixture, dilute with ethyl acetate (˜40 mL) and partition the layers in a separatory funnel. Dry the organic layer over solid magnesium sulfate, filter, then apply to a 10 g SCX Mega Bond-Elut™ cartridge (Varian) prewashed with 100 mL 1:1 CH2Cl2:MeOH. After loading, wash the cartridge with another 200-250 mL of the CH2Cl2:MeOH solution, then elute the product with 100 mL of CH2Cl2:2 M NH3-MeOH, concentrate to a brown-orange oil, and purify via flash chromatography with a gradient of 0 to 5% methanol in dichloromethane. Pool the clean fractions and concentrate to provide 750 mg (67%) of the title compound as a yellow-brown solid after drying. MS (ES) m/z 293 (M+1).

Workup

  1. customdeoxygenate with vacuum/nitrogen bubbling
  2. temperatureCool the dark brown reaction mixture
  3. custompartition the layers in a separatory funnel
  4. dry with materialDry the organic layer over solid magnesium sulfate
  5. filtrationfilter
  6. washwash the cartridge with another 200-250 mL of the CH2Cl2
  7. washMeOH solution, then elute the product with 100 mL of CH2Cl2
  8. concentration2 M NH3-MeOH, concentrate to a brown-orange oil
  9. custompurify via flash chromatography with a gradient of 0 to 5% methanol in dichloromethane
  10. concentrationconcentrate

Sources & evidence

ORD record
ord-b9f0cd2c6ebe46209d20bc6e16d3bdb5
Source dataset
uspto-grants-2010_02
Patent number
US07666879B2

Reaction notes

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