4-(Tetramethyl-1,3,2-dioxaborolan-2-yl)aniline → 4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)aniline

HRID 1093216Notes

Reaction equation

HRID 1093216 reaction equation
Cl[C:2]1[N:7]=[C:6]2[N:8]([CH3:11])[N:9]=[CH:10][C:5]2=[C:4]([N:12]2[CH2:18][CH:17]3[O:19][CH:14]([CH2:15][CH2:16]3)[CH2:13]2)[N:3]=1.[NH2:20][C:21]1[CH:26]=[CH:25][C:24](B2OC(C)(C)C(C)(C)O2)=[CH:23][CH:22]=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:14]12[O:19][CH:17]([CH2:16][CH2:15]1)[CH2:18][N:12]([C:4]1[N:3]=[C:2]([C:24]3[CH:25]=[CH:26][C:21]([NH2:20])=[CH:22][CH:23]=3)[N:7]=[C:6]3[N:8]([CH3:11])[N:9]=[CH:10][C:5]=13)[CH2:13]2

Participants

6

Reactant 2

HCID 27346204-(Tetramethyl-1,3,2-dioxaborolan-2-yl)anilineHCID 86629377HCID 86629377, compound

Product 1

HCID 665889994-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)aniline

Reagents, catalysts & solvents 3

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

Conditions

Temperature
120 °C

Procedure

A mixture of 3-(6-chloro-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-4-yl)-8-oxa-3-azabicyclo[3.2.1]octane (0.40 g, 1.4 mmol), 4-aminophenylboronic acid pinacol ester (0.47 g, 2.1 mmol), and tetrakis(triphenylphosphine)palladium(0) (0.16 g, 10 mol %) in toluene/ethanol (1:1, 7 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 triturated with dichloromethane and the light brown solid was collected by Buchner filtration to furnish 4-(4-(8-oxa-3-azabicyclo[3.2.1]octan-3-yl)-1-methyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)aniline. MS (ES+): 337.0 (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 triturated with dichloromethane
  8. filtrationthe light brown solid was collected by Buchner filtration

Sources & evidence

ORD record
ord-42d7ff1d40894553836a965e3137b98a
Source dataset
uspto-grants-2012_03
Patent number
US08129371B2

Reaction notes

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