Triethylamine → 3-(4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)phenol

HRID 1093192Notes

Reaction equation

Br[C:2]1[N:7]=[C:6]([C:8]2[CH:9]=[C:10]([OH:14])[CH:11]=[CH:12][CH:13]=2)[N:5]=[C:4]2[N:15]([C:18]3[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=3)[N:16]=[CH:17][C:3]=12.Cl.[CH:25]12[NH:32][CH:29]([CH2:30][CH2:31]1)[CH2:28][O:27][CH2:26]2.C(N(CC)CC)C>C(O)C>[CH:29]12[N:32]([C:2]3[N:7]=[C:6]([C:8]4[CH:9]=[C:10]([OH:14])[CH:11]=[CH:12][CH:13]=4)[N:5]=[C:4]4[N:15]([C:18]5[CH:23]=[CH:22][CH:21]=[CH:20][CH:19]=5)[N:16]=[CH:17][C:3]=34)[CH:25]([CH2:31][CH2:30]1)[CH2:26][O:27][CH2:28]2

Participants

Conditions

Temperature: 130 °C

Procedure

A Smith process vial was charged with a suspension of 3-(4-bromo-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)phenol (0.18 g, 0.49 mmol) and 3-oxa-8-azabicyclo[3.2.1]octane hydrochloride (approximately 100 mg, 0.67 mmol) in ethanol (4 mL). The suspension was treated with triethylamine (750 μL, 5.7 mmol) and was then heated in the microwave reactor for 10 minutes at 130° C. The reaction mixture was concentrated to dryness under reduced pressure, and the residue was purified by reverse-phase high performance liquid chromatography using a Phenomenex Prodigy 21 mm×250 mm column, running a gradient elution of 20% acetonitrile/80% of 0.1% aqueous trifluoroacetic acid to 100% acetonitrile to provide 3-(4-(3-oxa-8-azabicyclo[3.2.1]octan-8-yl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl)phenol. MS (ES+): 400.3 (M+H)+

Workup

concentrationThe reaction mixture was concentrated to dryness under reduced pressure
customthe residue was purified by reverse-phase high performance liquid chromatography
washa gradient elution of 20% acetonitrile/80% of 0.1% aqueous trifluoroacetic acid to 100% acetonitrile

Sources & evidence

ORD record: ord-f92e54834bd04caea2a48b9ecd1a843c
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08129371B2

Reaction notes

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