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

HRID 1093193Notes

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

Participants

Conditions

Temperature: 180 °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 (0.15 g, 0.41 mmol) and 8-oxa-3-azabicyclo[3.2.1]octane hydrochloride (approximately 1 mmol) in ethanol (5 mL). The suspension was treated with triethylamine (500 μL, 3.8 mmol) and was then heated in the microwave reactor for 10 minutes at 180° 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 15% acetonitrile/88% of 0.1% aqueous trifluoroacetic acid to 100% acetonitrile to provide 3-[4-(8-oxa-3-azabicyclo[3.2.1]oct-3-yl)-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl]phenol. MS (ES+): 400.1 (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 15% acetonitrile/88% of 0.1% aqueous trifluoroacetic acid to 100% acetonitrile

Sources & evidence

ORD record: ord-0ad18b9d89f6460f9f39caf87def58f4
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08129371B2

Reaction notes

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