4-(Dimethylamino)Benzaldehyde → 2-(4-(6-chloro-2-(4-(dimethylamino)phenyl)-3H-imidazo(4,5-b)pyridin-7-yl)piperazin-1-yl)-N-(thiazol-2-yl)acetamide

HRID 416695

Reaction equation

[NH2:1][C:2]1[C:7]([N+:8]([O-])=O)=[C:6]([N:11]2[CH2:16][CH2:15][N:14]([CH2:17][C:18]([NH:20][C:21]3[S:22][CH:23]=[CH:24][N:25]=3)=[O:19])[CH2:13][CH2:12]2)[C:5]([Cl:26])=[CH:4][N:3]=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:26][C:5]1[C:6]([N:11]2[CH2:16][CH2:15][N:14]([CH2:17][C:18]([NH:20][C:21]3[S:22][CH:23]=[CH:24][N:25]=3)=[O:19])[CH2:13][CH2:12]2)=[C:7]2[N:8]=[C:33]([C:32]3[CH:35]=[CH:36][C:29]([N:28]([CH3:37])[CH3:27])=[CH:30][CH:31]=3)[NH:1][C:2]2=[N:3][CH:4]=1

Participants

Conditions

Temperature: 70 °C

Procedure

To a mixture of 2-[4-(2-Amino-5-chloro-3-nitro-pyridin-4-yl)-piperazin-1-yl]-N-thiazol-2-yl-acetamide (0.040 g, 0.10 mmol), ethanol (3 ml), and 4-dimethylamino-benzaldehyde (0.019 g, 0.13 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 3.5 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 ethyl acetate/dichloromethane (v/v; 1:1), 1.5% methanol in ethyl acetate/dichloromethane (v/v; 1:1) and finally 2% methanol in ethyl acetate/dichloromethane (v/v; 1:1). The title compound was obtained after trituration with diethyl ether as a pale yellow solid (0.005 g, 10%); 1H-NMR (250 Mz, DMSO-d6) 2.78 (m, 4H, piperazine N(CH2)2), 3.01 (s, 6H, N(CH3)2), 3.40 (s, 2H, NCH2CO), 3.72 (m, 4H, piperazine N(CH2)2), 6.83 (d, J=8.79 Hz, 2H, 3,5-ArH or 2,6-ArH), 7.25 (d, J=3.42 Hz, 1H) and 7.51 (d, J=3.53 Hz, 1H) (thiazole 4-H, 5-H), 8.03 (d, 3H, J=9.88 Hz, 3,5-ArH or 2,6-ArH, and imidazo[4,5-b]pyridine 5-H); 11.95 (s, 1H, CONH), 13.12 (s, 1H, imidazo[4,5-b]pyridine N—H); LC-MS (ESI, m/z) 6.17 min—497, 499 [(M+H)+, Cl isotopic pattern]; ESI-HRMS Found: 497.1652, calculated for C23H26N8ClOS (M+H)+: 497.1633.

Workup

temperatureto cool to room temperature
customthe solvents were removed in vacuo
customThe residue was absorbed on silica gel
washwas eluted with ethyl acetate/dichloromethane (v/v; 1:1), 1.5% methanol in ethyl acetate/dichloromethane (v/v; 1:1) and finally 2% methanol in ethyl acetate/dichloromethane (v/v; 1:1)

Sources & evidence

ORD record: ord-4431fa50aa804dc5a193597c27fdb40e
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08088761B2

Linked notes

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