4-(Dimethylamino)Benzaldehyde → (4-{6-Chloro-7-[4-(2-phenoxy-ethyl)-piperazin-1-yl]-3H-imidazo[4,5-b]pyridin-2-yl}-phenyl)-dimethyl-amine

HRID 416706Notes

Reaction equation

[Cl:1][C:2]1[C:3]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][O:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:14][CH2:13]2)=[C:4]([N+:9]([O-])=O)[C:5]([NH2:8])=[N:6][CH:7]=1.[CH3:27][N:28]([CH3:37])[C:29]1[CH:36]=[CH:35][C:32]([CH:33]=O)=[CH:31][CH:30]=1.[O-]S(S([O-])=O)=O.[Na+].[Na+]>C(O)C>[Cl:1][C:2]1[C:3]([N:12]2[CH2:17][CH2:16][N:15]([CH2:18][CH2:19][O:20][C:21]3[CH:26]=[CH:25][CH:24]=[CH:23][CH:22]=3)[CH2:14][CH2:13]2)=[C:4]2[N:9]=[C:33]([C:32]3[CH:35]=[CH:36][C:29]([N:28]([CH3:37])[CH3:27])=[CH:30][CH:31]=3)[NH:8][C:5]2=[N:6][CH:7]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a mixture of 5-chloro-3-nitro-4-[4-(2-phenoxy-ethyl)-piperazin-1-yl]-pyridin-2-ylamine (0.037 g, 0.10 mmol), ethanol (3 ml), and 4-dimethylamino-benzaldehyde (0.021 g, 0.14 mmol) was added a freshly prepared aqueous solution of Na2S2O4 (1M; 0.4 ml, 0.4 mmol). The reaction mixture was heated at 70° C. for 5.5 h, then allowed to cool to room temperature and the solvents were removed in vacuo. The residue was absorbed on silica gel and the free running powder was placed on a 10 g isolute silica column, which was eluted with 1 to 2.5% gradient of methanol in ethyl acetate/dichloromethane (v/v; 1:1). The title compound was isolated as a pale yellow solid after trituration with diethyl ether (0.011 g, 23%); %); 1H-NMR (500 Mz, DMSO-d6) 2.72 (br s, 4H, piperazine N(CH2)2), 2.79 (t, J=5.46 Hz, 2H, NCH2CH2O), 3.68 (br s, 4H, piperazine N(CH2)2), 4.15 (t, J=5.70 Hz, 2H, NCH2CH2O), 6.82 (d, J=10.17 Hz, 2H) and 8.00 (d, J=8.93 Hz, 2H) (3,5-C6H4—NMe2 and 3,5-C6H4—NMe2) 6.93 (t, J=6.7 Hz, 1H, p-ArH), 6.99 (d, J=8.92 Hz, 2H, o-ArH), 7.30 (t, J=8.16 Hz, 2H, m-ArH), 8.03 (s, 1H, imidazo[4,5-b]pyridine 5-H), 13.10 (s, 1H, imidazo[4,5-b]pyridine N—H); LC-MS (ESI, m/z) 5.57 min—477, 479 [(M+H)+, Cl isotopic pattern]; ESI-HRMS: Found: 477.2162, calculated for C26H30N6OCl (M+H)+: 477.2170.

Workup

temperatureto cool to room temperature
customthe solvents were removed in vacuo
customThe residue was absorbed on silica gel
washwas eluted with 1 to 2.5% gradient of methanol in ethyl acetate/dichloromethane (v/v; 1:1)

Sources & evidence

ORD record: ord-29e27f5cd382424d997533e48eb81aad
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08088761B2

Reaction notes

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