Acetic Acid → HCID 178480996, compound

HRID 432220Notes

Reaction equation

HRID 432220 reaction equation
[CH3:1][N:2]1[CH2:7][CH2:6][N:5]([C@@H:8]2[CH2:13][CH2:12][C@H:11]([N:14]3[C:18]4=[N:19][CH:20]=[N:21][C:22]([NH2:23])=[C:17]4[C:16]([C:24]4[CH:29]=[CH:28][C:27]([O:30][C:31]5[CH:36]=[CH:35][CH:34]=[CH:33][C:32]=5[N+:37]([O-])=O)=[CH:26][CH:25]=4)=[N:15]3)[CH2:10][CH2:9]2)[CH2:4][CH2:3]1.C(O)(=O)C>C(O)C.[Pd]>[NH2:37][C:32]1[CH:33]=[CH:34][CH:35]=[CH:36][C:31]=1[O:30][C:27]1[CH:26]=[CH:25][C:24]([C:16]2[C:17]3[C:18](=[N:19][CH:20]=[N:21][C:22]=3[NH2:23])[N:14]([C@H:11]3[CH2:12][CH2:13][C@@H:8]([N:5]4[CH2:6][CH2:7][N:2]([CH3:1])[CH2:3][CH2:4]4)[CH2:9][CH2:10]3)[N:15]=2)=[CH:29][CH:28]=1

Participants

5

Reactant 2

HCID 176Acetic AcidHCID 178480997HCID 178480997, compound

Product 1

HCID 178480996HCID 178480996, compoundYield 39.6%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 702EthanolSolvent

Procedure

A mixture of cis-1-[4-(4-methylpiperazino)cyclohexyl]-3-[4-(2nitrophenoxy)phenyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine (0.059 g, 0.091 mmol, 1 equiv), glacial acetic acid (0.03 mL, 0.5 mmol, 5 equiv), and 10% Pd-C (0.024 g, 0.4 wt/wt equiv) in ethanol (1 mL) was stirred at room temperature under a positive pressure of H2 for 16 h. Solids were removed by filtration with the aid of CH2Cl2 (10 mL) and the filtrate was concentrated to afford a yellow oil. 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 afford cis-3-[4-(2-aminophenoxy)phenyl]-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine as an off-white solid (0.018 g, 0.036 mmol): 1H NMR (d6 DMSO, 400 MHz): δ H 8.22 (1H, s), 7.59 (2H, d, J=8.6 Hz), 7.05 (2H, d, J=8.7 Hz), 6.85-6.98 (3H, m), 6.58-6.61 (1H, m), 4.93 (2H, bs), 4.78-4.80 (1H, m), 2.20-2.50 (11H, m), 2.14 (3H, s), 2.05-2.09 (2H, m), 1.55-1.70 (4H, 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 12.00 min. MS: MH+ 499.

Workup

  1. customSolids were removed by filtration with the aid of CH2Cl2 (10 mL)
  2. concentrationthe filtrate was concentrated
  3. customto afford a yellow oil
  4. 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)
  5. customThe acetonitrile was removed in vacuo

Sources & evidence

ORD record
ord-329d50d21ef5404a99fd31e579b78035
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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