Ethanol → 6-Chloro-2-(4-morpholin-4-ylmethyl-phenyl)-7-(4-pyridin-3-ylmethyl-piperazin-1-yl)-3H-imidazo[4,5-b]pyridine

HRID 416812Notes

Reaction equation

HRID 416812 reaction equation
[Cl:1][C:2]1[C:3]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][C:19]3[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=3)[CH2:14][CH2:13]2)=[C:4]([N+:9]([O-])=O)[C:5]([NH2:8])=[N:6][CH:7]=1.CCO.[N:28]1([CH2:34][C:35]2[CH:42]=[CH:41][C:38]([CH:39]=O)=[CH:37][CH:36]=2)[CH2:33][CH2:32][O:31][CH2:30][CH2:29]1.[O-]S(S([O-])=O)=O.[Na+].[Na+]>C(OCC)C>[Cl:1][C:2]1[C:3]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][C:19]3[CH:20]=[N:21][CH:22]=[CH:23][CH:24]=3)[CH2:14][CH2:13]2)=[C:4]2[N:9]=[C:39]([C:38]3[CH:37]=[CH:36][C:35]([CH2:34][N:28]4[CH2:33][CH2:32][O:31][CH2:30][CH2:29]4)=[CH:42][CH:41]=3)[NH:8][C:5]2=[N:6][CH:7]=1

Participants

6

Reactant 4

HCID 702EthanolHCID 24489Sodium DithioniteHCID 27954984-[(Morpholin-4-yl)methyl]benzaldehydeHCID 578972325-Chloro-3-nitro-4-(4-(pyridin-3-ylmethyl)piperazin-1-yl)pyridin-2-amine

Product 1

HCID 1784782676-Chloro-2-(4-morpholin-4-ylmethyl-phenyl)-7-(4-pyridin-3-ylmethyl-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-chloro-3-nitro-4-(4-pyridin-3-ylmethyl-piperazin-1-yl)-pyridin-2-ylamine (0.031 g, 0.09 mmol) and EtOH (3.0 ml) was added 4-morpholin-4-ylmethyl-benzaldehyde (0.025 g, 0.12 mmol) followed by a freshly prepared aqueous solution of Na2S2O4 (1M; 0.36 ml, 0.36 mmol). The reaction mixture was stirred at 80° C. for 20 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 (2 to 13%) in ethyl acetate/dichloromethane (v:v; 4:1) afforded a yellow solid. The title compound was obtained as a pale yellow solid after trituration with diethyl ether (0.014 g, 30%); 1H-NMR (500 MHz, DMSO-d6) 2.38 (br s, 4H) and 3.59 (t, J=4.5 Hz, 4H) (morpholine N(CH2)2 and morpholine O(CH2)2), 2.62 (br s, 4H, piperazine N(CH2)2), 3.53 (s, 2H) and 3.61 (s, 2H) (NCH2-pyridyl and C6H4CH2N), 3.71 (br s, 4H, piperazine N(CH2)2), 7.39 (dd, J=5.30, 8.2 Hz, pyridine 5-H), 7.47 (d, J=8.2 Hz, 2H) and 8.12 (d, J=8.7 Hz, 2H) (3,5-C6H4— and 2,6-C6H4—), 7.78 (d, J=6.9 Hz, 1H, pyridine 4-H), 8.14 (s, 1H, imidazo[4,5-b]pyridine 5-H), 8.50 (dd, J=1.50, 4.6 Hz, 1H, pyridine 6-H), 8.56 (d, J=1.5 Hz, 1H, pyridine 2-H), 13.42 (br s, 1H, 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 (2 to 13%) in ethyl acetate/dichloromethane (v:v; 4:1)
  5. customafforded a yellow solid

Sources & evidence

ORD record
ord-78a9421d92a242339f181609e5dd9fef
Source dataset
uspto-grants-2012_01
Patent number
US08088761B2

Reaction notes

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