4-Aminophenol → 4-[1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-phenylamine

HRID 1011293Notes

Reaction equation

[NH2:1][C:2]1[CH:7]=[CH:6][C:5]([OH:8])=[CH:4][CH:3]=1.CN(C=O)C.[H-].[Na+].Cl[C:17]1[N:22]=[CH:21][N:20]=[C:19]2[N:23]([CH:26]3[CH2:31][CH2:30][CH2:29][CH2:28][O:27]3)[N:24]=[CH:25][C:18]=12>C(OCC)(=O)C>[O:27]1[CH2:28][CH2:29][CH2:30][CH2:31][CH:26]1[N:23]1[C:19]2=[N:20][CH:21]=[N:22][C:17]([O:8][C:5]3[CH:6]=[CH:7][C:2]([NH2:1])=[CH:3][CH:4]=3)=[C:18]2[CH:25]=[N:24]1

Participants

Conditions

Temperature: 0 °C

Procedure

To a round bottom flask equipped with a magnetic stir bar was added 4-amino-phenol (0.251 g, 2.3 mmol, 1.1 eq) and DMF (3 ml). The mixture was cooled to 0° C. followed by the addition of NaH (0.13, 5.4 mmol, 2.7 eq). After 10 minutes 4-Chloro-1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine (0.5 g, 2.1 mmol, 1.0 eq.) was added and the reaction was allowed to warm up to room temperature. After stirring at room temperature for 1 hour the reaction mixture was diluted with ethyl acetate (50 ml) and Was washed (2×) water, (1×) NaHCO3, (2×) 5% LiCl, and (1×) brine. The organic layer was dried over sodium sulfate and the solvent removed to give 4-[1-(tetrahydro-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yloxy]-phenylamine as a yellow solid (570 mg, 87%). 1H NMR (400 MHz, CDCl3): 8.56(s, 1H), 7.75 (s, 1H), 6.97 (d, 2H), 6.64 (d, 2H), 5.96 (dd, 1H), 5.21 (s, 2H), 3.96 (d, 1H), 3.72 (m, 1H), 2.42 (m, 1H), 2.01 (m, 1H), 1.87 (m, 1H), 1.76 (m, 1H), 1.57 (m, 2H); MS (ESI) for C16H17N5O2: 312 (MH+).

Workup

customTo a round bottom flask equipped with a magnetic stir bar
temperatureto warm up to room temperature
washWas washed (2×) water, (1×) NaHCO3, (2×) 5% LiCl, and (1×) brine
dry with materialThe organic layer was dried over sodium sulfate
customthe solvent removed

Sources & evidence

ORD record: ord-9baae3a319ed42cb9aa5f334036aedd5
Source dataset: uspto-grants-2011_07
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US07977345B2

Reaction notes

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