Triethylamine → 3-{4-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl]-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenol

HRID 1093205Notes

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.[C@H:25]12[CH2:31][C@H:28]([NH:29][CH2:30]1)[CH2:27][O:26]2.C(N(CC)CC)C>C(O)C>[C@H:25]12[CH2:31][C@H:28]([N:29]([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)[CH2:30]1)[CH2:27][O:26]2

Participants

Conditions

Temperature: 150 °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 (56 mg, 0.15 mmol) and (1S,4S)-2-oxa-5-azabicyclo[2.2.1]heptane hydrochloride (22 mg, 0.16 mmol) in ethanol (4 mL). The suspension was treated with triethylamine (59 μL, 0.45 mmol) and was then heated in the microwave reactor for 15 minutes at 150° 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 10% acetonitrile/90% of 0.1% aqueous trifluoroacetic acid to 75% acetonitrile to provide 3-{4-[(1S,4S)-2-oxa-5-azabicyclo[2.2.1]hept-5-yl]-1-phenyl-1H-pyrazolo[3,4-d]pyrimidin-6-yl}phenol. MS (ES+): 386.3 (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 10% acetonitrile/90% of 0.1% aqueous trifluoroacetic acid to 75% acetonitrile

Sources & evidence

ORD record: ord-9f606ea48d20445a89caf2d2314478e4
Source dataset: uspto-grants-2012_03
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08129371B2

Reaction notes

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