4-(Tetramethyl-1,3,2-dioxaborolan-2-yl)aniline → HCID 57424393, compound

HRID 1093170Notes

Reaction equation

HRID 1093170 reaction equation
[CH:1]12[O:8][CH:5]([CH2:6][CH2:7]1)[CH2:4][N:3]([C:9]1[N:14]=[C:13](Cl)[N:12]=[C:11]3[N:16]([CH:19]4[CH2:24][CH2:23][N:22]([C:25]([O:27][CH3:28])=[O:26])[CH2:21][CH2:20]4)[N:17]=[CH:18][C:10]=13)[CH2:2]2.[NH2:29][C:30]1[CH:35]=[CH:34][C:33](B2OC(C)(C)C(C)(C)O2)=[CH:32][CH:31]=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>[NH2:29][C:30]1[CH:35]=[CH:34][C:33]([C:13]2[N:12]=[C:11]3[N:16]([CH:19]4[CH2:20][CH2:21][N:22]([C:25]([O:27][CH3:28])=[O:26])[CH2:23][CH2:24]4)[N:17]=[CH:18][C:10]3=[C:9]([N:3]3[CH2:2][CH:1]4[O:8][CH:5]([CH2:6][CH2:7]4)[CH2:4]3)[N:14]=2)=[CH:32][CH:31]=1

Participants

6

Reactant 2

HCID 27346204-(Tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 75080609HCID 75080609, compound

Product 1

HCID 57424393HCID 57424393, compound

Reagents, catalysts & solvents 3

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

Conditions

Temperature
120 °C

Procedure

A suspension of methyl 4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-6-chloro-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate (2.3 mmol), 4-aminophenylboronic acid pinacol ester (0.76 g, 3.5 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.27 g, 10 mol %) in toluene/ethanol (1:1, 12 mL) and 2 M aqueous sodium carbonate solution (2.5 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 Gemini column, running a gradient elution of 20% acetonitrile/80% of 0.07% aqueous ammonium hydroxide to 95% acetonitrile over 10 minutes. After the concentration of fractions under reduced pressure, methyl 4-(6-(4-aminophenyl)-4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-1-yl)piperidine-1-carboxylate was obtained. MS (ES+): 464.6 (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 20% acetonitrile/80% of 0.07% aqueous ammonium hydroxide to 95% acetonitrile over 10 minutes

Sources & evidence

ORD record
ord-5b52f286ac0b4dec9954f9f7712fa5e8
Source dataset
uspto-grants-2012_03
Patent number
US08129371B2

Reaction notes

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