3-Nitrophenylboronic Acid → HCID 22347317, compound

HRID 897505Notes

Reaction equation

HRID 897505 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.[N+:23]([C:26]1[CH:27]=[C:28](B(O)O)[CH:29]=[CH:30][CH:31]=1)([O-:25])=[O:24].ClC(Cl)C.ClCCl>N1C=CC=CC=1.C([O-])(=O)C.[Cu+2].C([O-])(=O)C>[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:29]=[CH:28][CH:27]=[C:26]([N+:23]([O-:25])=[O:24])[CH:31]=4)=[CH:15][CH:16]=3)=[N:9]2)[CH2:22][CH2:21][CH2:20][CH2:19]1

Participants

7

Reactant 4

HCID 16773-Nitrophenylboronic AcidHCID 6344DichloromethaneHCID 63651,1-DichloroethaneHCID 135841424HCID 135841424, compound

Product 1

HCID 22347317HCID 22347317, compoundYield 11.8%

Reagents, catalysts & solvents 2

HCID 8895Cupric acetateCatalystHCID 1049PyridineSolvent

Procedure

A mixture of 4-(4-amino-1-cyclopentyl-1H-pyrazolo[3,4-d]pyrimidin-3-yl)phenol (0.202 g, 0.684 mmol, 1 equiv), 3-nitrophenylboronic acid (0.571 g, 3.42 mmol, 5.0 equiv), copper (II) acetate (0.186 g, 1.02 mmol, 1.5 equiv), and 4 Å molecular sieves in pyridine (0.28 mL) and dichloroethane (6.8 mL) was heated at reflux for 24 h. The reaction mixture was allowed to cool to ambient temperature. Dichloromethane (25 mL) was added to the residue and the resulting solid was removed by filtration through a pad of Celite with the aid of MeOH (20 mL). The filtrate was concentrated to afford a brown liquid which was purified by column chromatography over silica gel (elution with 400 mL of heptane, 400 mL of 10% EtOAc/heptane, 400 mL of 20% EtOAc/heptane, and 800 mL of MeOH) to afford a red oil which was further purified by preparative RP-LC/MS (Gilson-Micromass C18, 5 μm, 130 Å, 21 cm, 0%-100% acetonitrile-0.1M ammonium acetate over 9 min, 25 mL/min). The acetonitrile was removed in vacuo and the aqueous mixture was lyopholyzed to give 1-cyclopentyl-3-[4-(3-nitrophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine as a pale yellow solid (0.034 g, 0.081 mmol): 1H NMR (d6 DMSO, 400 MHz): δH 8.22 (1H, s), 7.28-7.74 (6H, m), 7.18 (2H, d, J=8.6 Hz), 7.7 (2H, bs), 5.13-5.26 (1H, m), 2.02-2.10 (4H, m), 1.89-1.91 (2H, m), 1.68-1.70 (2H, m); RP-HPLC (Hypercil C18, 5 μm, 100 Å, 15 cm; 5%-100% acetonitrile-0.1M ammonium acetate over 15 min, 1 mL/min) Rt 19.98 min.

Workup

  1. temperatureat reflux for 24 h
  2. customthe resulting solid was removed by filtration through a pad of Celite with the aid of MeOH (20 mL)
  3. concentrationThe filtrate was concentrated
  4. customto afford a brown liquid which
  5. customwas purified by column chromatography over silica gel (elution with 400 mL of heptane, 400 mL of 10% EtOAc/heptane, 400 mL of 20% EtOAc/heptane, and 800 mL of MeOH)
  6. customto afford a red oil which
  7. customwas further purified by preparative RP-LC/MS (Gilson-Micromass C18, 5 μm, 130 Å, 21 cm, 0%-100% acetonitrile-0.1M ammonium acetate over 9 min, 25 mL/min)
  8. customThe acetonitrile was removed in vacuo

Sources & evidence

ORD record
ord-a2f3a9fb17e8430088e48e074cdd0d9a
Source dataset
uspto-grants-2005_07
Patent number
US06921763B2

Reaction notes

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