Potassium Carbonate → HCID 22346870, compound

HRID 897635Notes

Reaction equation

HRID 897635 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([CH:18]3[CH2:22][CH2:21][CH2:20][CH2:19]3)[N:9]=[C:10]([C:11]3[CH:16]=[CH:15][C:14]([OH:17])=[CH:13][CH:12]=3)[C:3]=12.C(=O)([O-])[O-].[K+].[K+].Br[C:30]1[CH:34]=[CH:33][S:32][CH:31]=1>CN(C=O)C.[Cu]>[CH:18]1([N:8]2[C:4]3=[N:5][CH:6]=[N:7][C:2]([NH2:1])=[C:3]3[C:10]([C:11]3[CH:12]=[CH:13][C:14]([O:17][C:30]4[CH:34]=[CH:33][S:32][CH:31]=4)=[CH:15][CH:16]=3)=[N:9]2)[CH2:22][CH2:21][CH2:20][CH2:19]1

Participants

6

Reactant 3

HCID 11430Potassium CarbonateHCID 133833-BromothiopheneHCID 135841424HCID 135841424, compound

Product 1

HCID 22346870HCID 22346870, compoundYield 22.3%

Reagents, catalysts & solvents 2

HCID 23978CopperCatalystHCID 6228DimethylformamideSolvent

Conditions

Temperature
153 °C

Procedure

A mixture of 4-(4-amino-1-cyclopentyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenol (0.212 g, 0.718 mmol, 1 equiv), potassium carbonate (0.060 g, 0.43 mmol, 0.6 equiv), copper powder (0.015 g, 0.24 mmol, 0.33 equiv), and 3-bromothiophene (0.09 mL, 0.9 mmol, 1.3 equiv) in DMF (7.2 mL) was heated at 153° C. for 24 hr. The reaction mixture was allowed to cool to ambient temperature, concentrated, and the residue was purified by preparative RP-HPLC (Rainin C18, 8 μm, 300 Å, 25 cm; 10%-60% acetonitrile-0.1M ammonium acetate over 20 min, 21 mL/min). The acetonitrile was removed in vacuo and the aqueous mixture was lyopholyzed to give 1-cyclopentyl-3-[4-(3-thienyloxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine as a light brown solid (0.060 g, 0.16 mmol): 1H NMR (d6 DMSO, 400 MHz): δH 9.77 (1H, s), 8.46 (1H, s), 8.41 (1H, s), 7.73-7.74 (1H, m), 7.57 (2H, d, J=4.5 Hz), 7.46-7.48 (1H, m), 7.15 (1H, d, J=5.2 Hz), 6.96 (2H, d, J=8.6 Hz), 5.24-5.30 (1H, m), 2.03-2.05 (4H, m), 1.89-1.93 (2H, m), 1.70-1.72 (2H, m). RP-HPLC (Delta Pak C18, 5 μm, 300 Å, 15 cm; 5%-85% acetonitrile-0.1M ammonium acetate over 20 min, 1 mL/min) Rt 18.76 min. MS: MH+ 378.

Workup

  1. temperatureto cool to ambient temperature
  2. concentrationconcentrated
  3. customthe residue was purified by preparative RP-HPLC (Rainin C18, 8 μm, 300 Å, 25 cm; 10%-60% acetonitrile-0.1M ammonium acetate over 20 min, 21 mL/min)
  4. customThe acetonitrile was removed in vacuo

Sources & evidence

ORD record
ord-9984707eecad4cbb8ce348f0aff34ea7
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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