Sodium Carbonate → N-(3-(6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)acrylamide

HRID 1500790Notes

Reaction equation

HRID 1500790 reaction equation
Cl[C:2]1[N:7]=[C:6]([Cl:8])[N:5]=[C:4]2[N:9]([CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)[N:10]=[CH:11][C:3]=12.[C:18]([NH:22][C:23]1[CH:24]=[C:25](B(O)O)[CH:26]=[CH:27][CH:28]=1)(=[O:21])[CH:19]=[CH2:20].C1(P(C2C=CC=CC=2)C2C=CC=CC=2)C=CC=CC=1.C(=O)([O-])[O-].[Na+].[Na+]>C1(C)C=CC=CC=1.C([O-])(=O)C.[Pd+2].C([O-])(=O)C>[Cl:8][C:6]1[N:5]=[C:4]2[N:9]([CH:12]3[CH2:17][CH2:16][CH2:15][CH2:14][O:13]3)[N:10]=[CH:11][C:3]2=[C:2]([C:25]2[CH:24]=[C:23]([NH:22][C:18](=[O:21])[CH:19]=[CH2:20])[CH:28]=[CH:27][CH:26]=2)[N:7]=1

Participants

7

Reactant 4

HCID 10340Sodium CarbonateHCID 11776TriphenylphosphineHCID 103213313-Acrylamidophenylboronic acidHCID 576542774,6-dichloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine

Product 1

HCID 86677518N-(3-(6-chloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidin-4-yl)phenyl)acrylamide

Reagents, catalysts & solvents 2

HCID 167845palladium(II) acetateCatalystHCID 1140TolueneSolvent

Conditions

Temperature
80 °C

Procedure

4,6-Dichloro-1-(tetrahydro-2H-pyran-2-yl)-1H-pyrazolo[3,4-d]pyrimidine (100 mg, 0.366 mmol), (3-acrylamidophenyl)boronic acid (70 mg, 0.366 mmol) and triphenylphosphine (4 mg, 0.015 mmol) were dissolved in a mixture of toluene (7 mL) and 1 M sodium carbonate (39 mg, 0.367 mmol), after which palladium(II) acetate (2.0 mg, 0.009 mmol) was added and the reaction mixture was stirred for 36 h at 80° C. The reaction was allowed to cool to room temperature, and the solvent was removed in vacuo. The residue was dissolved in ethyl acetate (20 mL) and washed with water (10 mL). The organic layer was separated, the aqueous layer was extracted with ethyl acetate (20 mL), the combined organic layers were washed with brine (20 mL), and dried over Na2SO4 and concentrated. The crude material was purified by flash chromatography (20% ethyl acetate/hexane) to yield the title compound. 1H NMR (400 MHz, CDCl3): δ 8.45 (m, 2H), 7.88 (d, 1H, J=8.0 Hz), 7.85 (d, 1H, J=8.0 Hz), 7.68 (s, 1H), 7.49 (t, 1H, J=8.0 Hz), 6.46 (m, 1H), 6.27 (m, 1H), 6.06 (d, 1H, J=10.4 Hz), 5.79 (d, 1H, J=10.0 Hz), 4.12 (m, 1H), 3.82 (t, 1H, J=10.0 Hz), 2.58 (m, 1H), 2.14 (m, 1H), 1.95 (m, 1H), 1.78 (m, 2H), 1.62 (m, 1H); ESI-MS: 384.10 [M+H]+.

Workup

  1. temperatureto cool to room temperature
  2. customthe solvent was removed in vacuo
  3. dissolutionThe residue was dissolved in ethyl acetate (20 mL)
  4. washwashed with water (10 mL)
  5. customThe organic layer was separated
  6. extractionthe aqueous layer was extracted with ethyl acetate (20 mL)
  7. washthe combined organic layers were washed with brine (20 mL)
  8. dry with materialdried over Na2SO4
  9. concentrationconcentrated
  10. customThe crude material was purified by flash chromatography (20% ethyl acetate/hexane)

Sources & evidence

ORD record
ord-8f669f6037e5493e9d35ccde266e2824
Source dataset
uspto-grants-2015_12
Patent number
US09206176B2

Reaction notes

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