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

HRID 1910008Notes

Reaction equation

HRID 1910008 reaction equation
[CH2:1]([N:3]1[C:7]2=[N:8][CH:9]=[N:10][C:11]([NH2:12])=[C:6]2[C:5](I)=[N:4]1)[CH3:2].[CH3:14][C:15]1[CH:16]=[C:17]([CH2:21][C:22]([N:24]2[C:32]3[C:27](=[CH:28][C:29](B4OC(C)(C)C(C)(C)O4)=[CH:30][CH:31]=3)[CH2:26][CH2:25]2)=[O:23])[CH:18]=[CH:19][CH:20]=1.C(=O)(O)[O-].[Na+].O1CCOCC1>O>[CH2:1]([N:3]1[C:7]2=[N:8][CH:9]=[N:10][C:11]([NH2:12])=[C:6]2[C:5]([C:29]2[CH:28]=[C:27]3[C:32](=[CH:31][CH:30]=2)[N:24]([C:22](=[O:23])[CH2:21][C:17]2[CH:18]=[CH:19][CH:20]=[C:15]([CH3:14])[CH:16]=2)[CH2:25][CH2:26]3)=[N:4]1)[CH3:2]

Participants

6

Reactant 4

HCID 312751,4-DioxaneHCID 516892Sodium BicarbonateHCID 668236371-ethyl-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amineHCID 668241231-[(3-methylphenyl)acetyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole

Product 1

HCID 534684681-ethyl-3-{1-[(3-methylphenyl)acetyl]-2,3-dihydro-1H-indol-5-yl}-1H-pyrazolo[3,4-d]pyrimidin-4-amine

Reagents, catalysts & solvents 1

HCID 962WaterSolvent

Conditions

Temperature
120 °C

Procedure

A 25 mL microwave pressure tube was charged 1-ethyl-3-iodo-1H-pyrazolo[3,4-d]pyrimidin-4-amine (105 mg, 0.363 mmol), 1-[(3-methylphenyl)acetyl]-5-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-2,3-dihydro-1H-indole (137 mg, 0.363 mmol), 1,1′-bis(diphenylphosphino)ferrocene-palladium(II)dichloride dichloromethane complex (14.83 mg, 0.018 mmol), and sodium bicarbonate (61.0 mg, 0.726 mmol) followed by dioxane (4 mL), and water (1 mL). The reaction was sealed and heated at 120° C. for 40 minutes in a microwave reactor. 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 50 mL of EtOAc was added to the mixture). The EtOAc solution was evaporated to dryness, and re-dissolved with CH2Cl2/MeOH (4 mL/1 mL). It was purified by flash column 25-100% EtOAc/hexane, then 0-10% MeOH/EtOAc (Analogix Si SF15-24g cartridge), to afford a brown solid. The brown solid was further purified by recrystallization from CH3CN to give the title compound as a brown solid. LC/MS (ES) m/z=413.3 [M+H]+. 1H NMR (400 MHz, DMSO-d6) ppm 1.41 (t, J=7.20 Hz, 3H), 2.31 (s, 3H), 3.21-3.29 (m, 2H), 3.85 (s, 2H), 4.23 (t, J=8.46 Hz, 2H), 4.32-4.40 (m, 2H), 7.07-7.14 (m, 3H), 7.21-7.28 (m, 1H), 7.44-7.46 (m, 1H), 7.51 (s, 1H), 8.21 (d, J=8.34 Hz, 1H), 8.24 (s, 1H).

Workup

  1. customThe reaction was sealed
  2. temperatureThe reaction was cooled to room temperature
  3. customthe mixture was transferred into a 100 mL flask
  4. washrinsed by EtOAc, with the water layer and black greasy solid
  5. customstayed in tube
  6. addition(total 50 mL of EtOAc was added to the mixture)
  7. customThe EtOAc solution was evaporated to dryness
  8. dissolutionre-dissolved with CH2Cl2/MeOH (4 mL/1 mL)
  9. customIt was purified by flash column 25-100% EtOAc/hexane
  10. custom0-10% MeOH/EtOAc (Analogix Si SF15-24g cartridge), to afford a brown solid
  11. customThe brown solid was further purified by recrystallization from CH3CN

Sources & evidence

ORD record
ord-9d9a15e707c34b2198e89991daedb02c
Source dataset
uspto-grants-2013_12
Patent number
US08598156B2

Reaction notes

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