Ethanol → 2-(4-((1H-Pyrazol-1-yl)methyl)phenyl)-6-bromo-7-(4-(4-chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridine

HRID 416819

Reaction equation

HRID 416819 reaction equation
[Br:1][C:2]1[C:3]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][C:19]3[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=3)[CH2:14][CH2:13]2)=[C:4]([N+:9]([O-])=O)[C:5]([NH2:8])=[N:6][CH:7]=1.CCO.[N:29]1([CH2:34][C:35]2[CH:42]=[CH:41][C:38]([CH:39]=O)=[CH:37][CH:36]=2)[CH:33]=[CH:32][CH:31]=[N:30]1.[O-]S(S([O-])=O)=O.[Na+].[Na+]>C(OCC)C>[N:29]1([CH2:34][C:35]2[CH:42]=[CH:41][C:38]([C:39]3[NH:8][C:5]4=[N:6][CH:7]=[C:2]([Br:1])[C:3]([N:12]5[CH2:17][CH2:16][N:15]([CH2:18][C:19]6[CH:24]=[CH:23][C:22]([Cl:25])=[CH:21][CH:20]=6)[CH2:14][CH2:13]5)=[C:4]4[N:9]=3)=[CH:37][CH:36]=2)[CH:33]=[CH:32][CH:31]=[N:30]1

Participants

6

Reactant 4

HCID 702EthanolHCID 24489Sodium DithioniteHCID 185258764-(1H-Pyrazol-1-ylmethyl)benzaldehydeHCID 468687815-Bromo-4-(4-(4-chlorobenzyl)piperazin-1-yl)-3-nitropyridin-2-amine

Product 1

HCID 1784781302-(4-((1H-Pyrazol-1-yl)methyl)phenyl)-6-bromo-7-(4-(4-chlorobenzyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridine

Reagents, catalysts & solvents 1

HCID 3283Diethyl EtherSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture of 5-bromo-4-[4-(4-chloro-benzyl)-piperazin-1-yl]-3-nitro-pyridin-2-ylamine (0.043 g, 0.10 mmol) and EtOH (4.0 ml) was added 4-pyrazol-1-ylmethyl-benzaldehyde (0.024 g, 0.13 mmol) followed by a freshly prepared aqueous solution of Na2S2O4 (1M; 0.40 ml, 0.40 mmol). The reaction mixture was stirred at 80° C. for 22 h, then allowed to cool to room temperature and concentrated in vacuo. The resulting residue was absorbed on silica, and the free-running powder was placed on a 10 g isolute silica column. Elution with a gradient of methanol (0 to 2%) in ethyl acetate/dichloromethane (v:v; 1:1) afforded a yellow solid. The title compound was obtained as a white solid after trituration with diethyl ether (0.023 g, 40%); 1H-NMR (500 MHz, DMSO-d6) 2.66 (br s, 4H, piperazine N(CH2)2), 3.56 (s, 2H, NCH2C6H4Cl), 3.66 (br s, 4H, piperazine N(CH2)2), 5.42 (s, 2H, C6H4CH2N), 6.30 (t, J=1.9 Hz, 1H, pyrazole 4-H), 7.35 (d, J=7.6 Hz, 2H) and 8.14 (d, J=8.3 Hz, 2H) (3,5-C6H4CH2N and 2,6-C6H4CH2N), 7.40 (m, 4H, C6H4Cl), 7.49 (d, J=1.5 Hz, 1H, pyrazole-H), 7.86 (d, J=1.8 Hz, 1H, pyrazole-H), 8.23 (s, 1H, imidazo[4,5-b]pyridine 5-H), 13.54 (br s, imidazo[4,5-b]pyridine N—H);

Workup

  1. temperatureto cool to room temperature
  2. concentrationconcentrated in vacuo
  3. customThe resulting residue was absorbed on silica
  4. washElution with a gradient of methanol (0 to 2%) in ethyl acetate/dichloromethane (v:v; 1:1)
  5. customafforded a yellow solid

Sources & evidence

ORD record
ord-fe5b03dc8dda4103ae3dd45f64af629e
Source dataset
uspto-grants-2012_01
Patent number
US08088761B2

Linked notes

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