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(3-hydroxyphenyl)boronic Acid → 3-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenol

HRID 1093218
Notes
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Reaction equation

HRID 1093218 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.[OH:20][C:21]1[CH:22]=[C:23](B(O)O)[CH:24]=[CH:25][CH:26]=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>[CH3:11][N:8]1[C:6]2=[N:7][C:2]([C:25]3[CH:26]=[C:21]([OH:20])[CH:22]=[CH:23][CH:24]=3)=[N:3][C:4]([N:12]3[CH2:18][CH:17]4[O:19][CH:14]([CH2:15][CH2:16]4)[CH2:13]3)=[C:5]2[CH:10]=[N:9]1
ParticipantsConditionsProcedureWorkupSources & evidenceReaction notes

Participants

6

Reactant 2

HCID 2734359(3-hydroxyphenyl)boronic AcidHCID 86629377HCID 86629377, compound

Product 1

HCID 252607563-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenol

Reagents, catalysts & solvents 3

HCID 178418397HCID 178418397, compoundCatalystHCID 10340
Sodium Carbonate
Solvent
HCID 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 (95 mg, 0.34 mmol), 3-hydroxyphenylboronic acid (70 mg, 0.51 mmol), and tetrakis(triphenylphosphine)palladium(0) (39 mg, 10 mol %) in toluene/ethanol (1:1, 3 mL) and 2 M aqueous sodium carbonate solution (2 mL) was heated in a 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 acidified with 1 M aqueous hydrochloric acid and then extracted three times with ethyl acetate. The combined extracts were washed successively with water, saturated aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride solution. The extracts were then 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 5% acetonitrile/95% of 0.1% aqueous trifluoroacetic acid to 90% acetonitrile to provide, after concentration, 3-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenol. MS (ES+): 338.0 (M+H)+

Workup

  1. customThe cooled mixture was partitioned between ethyl acetate and water
  2. extractionextracted three times with ethyl acetate
  3. washThe combined extracts were washed successively with water, saturated aqueous sodium hydrogen carbonate solution and saturated aqueous sodium chloride solution
  4. dry with materialThe extracts were then dried 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 5% acetonitrile/95% of 0.1% aqueous trifluoroacetic acid to 90% acetonitrile
  9. customto provide
  10. concentrationafter concentration, 3-[1-methyl-4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenol

Sources & evidence

ORD record
ord-aeb9dd17001142c59f6c8b64beb59fac
Source dataset
uspto-grants-2012_03
DOI
10.6084/m9.figshare.5104873.v1
Patent number
US08129371B2

Reaction notes

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