Glyoxal → HCID 178480959, compound

HRID 432351Notes

Reaction equation

HRID 432351 reaction equation
[NH2:1][C:2]1[N:7]=[CH:6][N:5]=[C:4]2[N:8]([C@H:26]3[CH2:31][CH2:30][C@@H:29]([N:32]4[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]4)[CH2:28][CH2:27]3)[N:9]=[C:10]([C:11]3[CH:12]=[C:13]([CH:23]=[CH:24][CH:25]=3)[O:14][C:15]3[CH:22]=[CH:21][CH:20]=[CH:19][C:16]=3[CH:17]=O)[C:3]=12.[CH:39]([CH:41]=O)=O.C(=O)([O-])[O-].[NH4+:47].[NH4+:48]>CO>[NH:47]1[CH:41]=[CH:39][N:48]=[C:17]1[C:16]1[CH:19]=[CH:20][CH:21]=[CH:22][C:15]=1[O:14][C:13]1[CH:12]=[C:11]([C:10]2[C:3]3[C:4](=[N:5][CH:6]=[N:7][C:2]=3[NH2:1])[N:8]([C@H:26]3[CH2:31][CH2:30][C@@H:29]([N:32]4[CH2:37][CH2:36][N:35]([CH3:38])[CH2:34][CH2:33]4)[CH2:28][CH2:27]3)[N:9]=2)[CH:25]=[CH:24][CH:23]=1

Participants

5

Reactant 3

HCID 7860Glyoxal2×HCID 517111Ammonium Carbonate2×HCID 178480961HCID 178480961, compound

Product 1

HCID 178480959HCID 178480959, compoundYield 9%

Reagents, catalysts & solvents 1

HCID 887MethanolSolvent

Procedure

A mixture of cis-2-(3-{4-amino-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-3-yl}phenoxy)benzaldehyde (0.102 g, 0.199 mmol, 1 equiv), glyoxal (0.12 mL, 0.99 mmol, 5 equiv), and ammonium carbonate (0.078 g, 0.99 mmol, 5 equiv) in methanol (1 mL) was stirred at ambient temperature for 16 h. Additional glyoxal (0.20 mL, 1.6 mmol, 8.3 equiv) and ammonium carbonate (0.130 g, 1.66 mmol, 8.4 equiv) were added and the reaction mixture was stirred at ambient temperature for 24 h. The crude reaction mixture 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 cis-3-{3-[2-(1H-2-imidazolyl)phenoxy]phenyl}-1-[4-(4-methylpiperazino)cyclohexyl]-1H-pyrazolo[3,4-d]pyrimidin-4-amine as a brown solid (0.010 g, 0.018 mmol): 1H NMR (d6 DMSO, 400 MHz): 6H 8.23 (1H, s), 8.11-8.13 (1H, dd, J=7.7, 1.9 Hz), 7.95 (1H, s), 7.66 (2H, d, J=8.5 Hz), 7.34-7.39 (1H, m), 7.23-7.27 (3H, m), 7.07-7.19 (3H, m), 4.77-4.82 (1H, m), 2.16-2.56 (11H, m), 2.14 (3H, s), 2.05-2.11 (2H, m), 1.55-1.71 (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 10.43 min. MS: MH+ 550.

Workup

  1. stirringthe reaction mixture was stirred at ambient temperature for 24 h
  2. customThe crude reaction mixture
  3. customwas 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-5f1f905f42f54a848ed4347387135c8b
Source dataset
uspto-grants-2003_12
Patent number
US06660744B1

Reaction notes

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