1,4-Dioxane → 2-(4-amino-3-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethanol

HRID 1910002Notes

Reaction equation

HRID 1910002 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][CH2:13][OH:14])[N:9]=[C:10](I)[C:3]=12.[CH3:15][C:16]1[CH:17]=[C:18]([CH2:22][C:23]([N:25]2[C:33]3[C:28](=[CH:29][C:30](B4OC(C)(C)C(C)(C)O4)=[CH:31][CH:32]=3)[CH2:27][CH2:26]2)=[O:24])[CH:19]=[CH:20][CH:21]=1.C(=O)(O)[O-].[Na+].O1CCOCC1>O>[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH2:12][CH2:13][OH:14])[N:9]=[C:10]([C:30]3[CH:29]=[C:28]4[C:33](=[CH:32][CH:31]=3)[N:25]([C:23](=[O:24])[CH2:22][C:18]3[CH:19]=[CH:20][CH:21]=[C:16]([CH3:15])[CH:17]=3)[CH2:26][CH2:27]4)[C:3]=12

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 22346783HCID 22346783, compoundHCID 668241231-[(3-methylphenyl)acetyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole

Product 1

HCID 668236622-(4-amino-3-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethanol

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

To a 25 mL pressure tube was charged 2-(4-amino-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-1-yl)ethanol (63.8 mg, 0.209 mmol), 1-[(3-methylphenyl)acetyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole (79 mg, 0.209 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (8.54 mg, 0.011 mmol), and sodium bicarbonate (35.1 mg, 0.418 mmol) followed by dioxane (8 mL), and water (2 mL). The reaction was heated at 120° C. for 40 min in microwave. The reaction was cooled to room temperature, the mixture was transferred into a 100 mL flask, rinsed by EtOAc, with the water layer and black greasy solid stayed in tube (total 100 mL of EtOAc was added to the mixture). The EtOAc solution was concentrated to dryness, and re-dissolved with CH2Cl2/MeOH (8 mL/2 mL). It was purified by flash column 25-100% EtOAc/hexane, then 0-10% MeOH/EtOAc, Si SF15-24g, to afford a brown solid. The brown solid was further purified by recrystallization in CH3CN to give a brown solid as the title compound. LC/MS (ES) m/z=429.4 [M+H]+. 1H NMR (400 MHz, DMSO-d6) δ ppm 2.31 (s, 3H), 3.24 (s, 2H), 3.80-3.88 (m, 4H), 4.19-4.27 (m, 2H), 4.37 (t, J=5.81 Hz, 2H), 4.89 (t, J=5.68 Hz, 1H), 7.07-7.14 (m, 3H), 7.20-7.28 (m, 1H), 7.45 (d, J=8.08 Hz, 1H), 7.51 (s, 1H), 8.21 (d, J=8.34 Hz, 1H), 8.23 (s, 1H).

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. customthe mixture was transferred into a 100 mL flask
  3. washrinsed by EtOAc, with the water layer and black greasy solid
  4. customstayed in tube
  5. addition(total 100 mL of EtOAc was added to the mixture)
  6. concentrationThe EtOAc solution was concentrated to dryness
  7. dissolutionre-dissolved with CH2Cl2/MeOH (8 mL/2 mL)
  8. customIt was purified by flash column 25-100% EtOAc/hexane
  9. custom0-10% MeOH/EtOAc, Si SF15-24g, to afford a brown solid
  10. customThe brown solid was further purified by recrystallization in CH3CN

Sources & evidence

ORD record
ord-3cc8331b423a4e9197211303bf392154
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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