4-(Tetramethyl-1,3,2-dioxaborolan-2-yl)aniline → HCID 66589022, compound

HRID 1093174Notes

Reaction equation

HRID 1093174 reaction equation
Cl[C:2]1[N:7]=[C:6]2[N:8]([CH:11]3[CH2:16][CH2:15][N:14]([CH2:17][C:18]([F:21])([F:20])[F:19])[CH2:13][CH2:12]3)[N:9]=[CH:10][C:5]2=[C:4]([N:22]2[CH2:28][CH:27]3[O:29][CH:24]([CH2:25][CH2:26]3)[CH2:23]2)[N:3]=1.[NH2:30][C:31]1[CH:36]=[CH:35][C:34](B2OC(C)(C)C(C)(C)O2)=[CH:33][CH:32]=1>C1(C)C=CC=CC=1.C(O)C.C(=O)([O-])[O-].[Na+].[Na+].C1C=CC([P]([Pd]([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)([P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)[P](C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)(C2C=CC=CC=2)C2C=CC=CC=2)=CC=1>[CH:27]12[O:29][CH:24]([CH2:25][CH2:26]1)[CH2:23][N:22]([C:4]1[N:3]=[C:2]([C:34]3[CH:35]=[CH:36][C:31]([NH2:30])=[CH:32][CH:33]=3)[N:7]=[C:6]3[N:8]([CH:11]4[CH2:12][CH2:13][N:14]([CH2:17][C:18]([F:19])([F:20])[F:21])[CH2:15][CH2:16]4)[N:9]=[CH:10][C:5]=13)[CH2:28]2

Participants

6

Reactant 2

HCID 27346204-(Tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 866293683-(6-Chloro-1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane

Product 1

HCID 66589022HCID 66589022, compound

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 10340Sodium CarbonateSolventHCID 21863594Toluene ethanolSolvent

Conditions

Temperature
120 °C

Procedure

A mixture of 3-(6-chloro-1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane (0.55 g, 1.3 mmol), 4-aminophenylboronic acid pinacol ester (0.42 g, 1.9 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.15 g, 10 mol %) in toluene/ethanol (1:1, 10 mL) and 2 M aqueous sodium carbonate solution (2 mL) was heated in a 10-20 mL Smith process vial in the microwave reactor for one hour at 120° C. The cooled mixture was partitioned between ethyl acetate and water. The aqueous phase was extracted three times with ethyl acetate. The combined extracts were washed with saturated aqueous sodium chloride solution, dried over anhydrous magnesium sulfate, filtered, and concentrated to dryness under reduced pressure. The crude residue was purified via reverse-phase high performance liquid chromatography using a Phenomenex Prodigy 21 mm×250 mm column, running a gradient elution of 10% acetonitrile/90% of 0.1% aqueous trifluoroacetic acid to 95% acetonitrile over 30 minutes. After the concentration of fractions under reduced pressure, 4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-(1-(2,2,2-trifluoroethyl)piperidin-4-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl)aniline was obtained as a maroon oil that solidified upon standing. MS (ES+): 488.4 (M+H)+

Workup

  1. customThe cooled mixture was partitioned between ethyl acetate and water
  2. extractionThe aqueous phase was extracted three times with ethyl acetate
  3. washThe combined extracts were washed with saturated aqueous sodium chloride solution
  4. dry with materialdried over anhydrous magnesium sulfate
  5. filtrationfiltered
  6. concentrationconcentrated to dryness under reduced pressure
  7. customThe crude residue was purified via reverse-phase high performance liquid chromatography
  8. washa gradient elution of 10% acetonitrile/90% of 0.1% aqueous trifluoroacetic acid to 95% acetonitrile over 30 minutes

Sources & evidence

ORD record
ord-7a42d4d7a7fe458d84548220f7b15727
Source dataset
uspto-grants-2012_03
Patent number
US08129371B2

Reaction notes

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