Sodium Dithionite → 6-Bromo-7-(4-(4-fluorobenzyl)piperazin-1-yl)-2-(4-methoxyphenyl)-3H-imidazo[4,5-b]pyridine

HRID 416892Notes

Reaction equation

HRID 416892 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]([F: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.[CH:26](=O)[C:27]1[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=1.[O-]S(S([O-])=O)=O.[Na+].[Na+]>CCO>[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]([F:25])=[CH:21][CH:20]=3)[CH2:14][CH2:13]2)=[C:4]2[N:9]=[C:26]([C:27]3[CH:32]=[CH:31][C:30]([O:33][CH3:34])=[CH:29][CH:28]=3)[NH:8][C:5]2=[N:6][CH:7]=1

Participants

5

Reactant 3

HCID 24489Sodium DithioniteHCID 312444-MethoxybenzaldehydeHCID 578972785-Bromo-4-(4-(4-fluorobenzyl)piperazin-1-yl)-3-nitropyridin-2-amine

Product 1

HCID 1784888696-Bromo-7-(4-(4-fluorobenzyl)piperazin-1-yl)-2-(4-methoxyphenyl)-3H-imidazo[4,5-b]pyridine

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent2×

Conditions

Temperature
85 °C

Procedure

To a mixture of 5-bromo-4-(4-(4-fluorobenzyl)piperazin-1-yl)-3-nitropyridin-2-amine (0.120 g, 0.30 mmol) and EtOH (5 mL), was added p-anisaldehyde (0.045 g, 0.33 mmol) in EtOH (1.8 mL), followed by a freshly prepared aqueous solution of Na2S2O4 (1M; 0.9 mL, 0.9 mmol). The reaction mixture was heated at 85° C. for 24 h, then allowed to cool to room temperature and the solvents were removed in vacuo. The residue was absorbed on silica gel and purified by column chromatography on a Biotage SP1 system eluting with methanol (2-10%) in dichloromethane. The title compound was isolated as a pale yellow solid after trituration with diethyl ether (0.010 g, 7%); 1H-NMR (500 Mz, DMSO-d6): δ 2.60 (m, 4H, piperazine N(CH2)2), 3.56 (s, 2H, NCH2), 3.65 (m, 4H, piperazine N(CH2)2), 3.84 (s, 3H, OMe), 7.10 (d, J=7.0 Hz, 2H, ArH, C6H4—OMe), 7.17 (br t, J=9.0 Hz, 2H, ArH, C6H4—F), 7.40 (br dd, J=8.5, 6.0 Hz, 2H, ArH, C6H4—F), 8.13 (d, J=9.0 Hz, 2H, ArH, C6H4—OMe), 8.20 (s, 1H, imidazo[4,5-b]pyridine 5-H), 13.34 (br s, 1H, imidazo[4,5-b]pyridine N—H); LC (Method B)-MS (ESI, m/z) 3.58 min—496/498 [(M+H)+, Br isotopic pattern]. ESI-HRMS: Found: 496.1144, calculated for C24H24BrFN5O (M+H)+: 496.1148.

Workup

  1. temperatureto cool to room temperature
  2. customthe solvents were removed in vacuo
  3. customThe residue was absorbed on silica gel
  4. custompurified by column chromatography on a Biotage SP1 system
  5. washeluting with methanol (2-10%) in dichloromethane

Sources & evidence

ORD record
ord-2125c2b997a54a0e8cf59b33ca362c7d
Source dataset
uspto-grants-2012_01
Patent number
US08088761B2

Reaction notes

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