4-(Dimethylamino)Benzaldehyde → 4-(6-chloro-7-(4-(1-phenylethyl)piperazin-1-yl)-3H-imidazo[4,5-b]pyridin-2-yl)-N,N-dimethylaniline

HRID 416716Notes

Reaction equation

[Cl:1][C:2]1[C:3]([N:12]2[CH2:17][CH2:16][N:15]([CH:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH3:19])[CH2:14][CH2:13]2)=[C:4]([N+:9]([O-])=O)[C:5]([NH2:8])=[N:6][CH:7]=1.[CH3:26][N:27]([CH3:36])[C:28]1[CH:35]=[CH:34][C:31]([CH:32]=O)=[CH:30][CH:29]=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]([CH:18]([C:20]3[CH:25]=[CH:24][CH:23]=[CH:22][CH:21]=3)[CH3:19])[CH2:14][CH2:13]2)=[C:4]2[N:9]=[C:32]([C:31]3[CH:34]=[CH:35][C:28]([N:27]([CH3:36])[CH3:26])=[CH:29][CH:30]=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-(1-phenylethyl)piperazin-1-yl)pyridin-2-amine (0.038 g, 0.10 mmol), ethanol (3 ml), and 4-dimethylamino-benzaldehyde (0.023 g, 0.15 mmol) was added a freshly prepared aqueous solution of Na2S2O4 (1M; 0.44 ml, 0.44 mmol). The reaction mixture was heated at 70° C. for 6 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 2.5% methanol in ethyl acetate/dichloromethane (v/v; 1:1). The obtained yellow solid was suspended in dichloromethane (2 ml), and then a solution of HCl in methanol (1.25 M; 0.8 ml) was added. The mixture was stirred for approximately 1 min, and then diethyl ether was added. The yellow precipitate was collected by filtration, washed with ether to afford the title compound as a hydrochloride salt. (0.013 g); 1H-NMR (500 Mz, CD3OD) 1.90 (d, J=5.43 Hz, 3H, CHCH3), 3.43 (m), 3.96 (m), 4.12 (m) (8H, piperazine N(CH2)2), 3.21 (s, 6H, N(CH3)2), 4.65 (m, 1H, NCHCH3), 7.14 (d, J=7.30 Hz, 2H) and 8.14 (d, J=7.32 Hz, 2H) (3,5-C6H4—NMe2 and 2,6-C6H4—NMe2) 7.55 (m, 3H) and 7.66 (m, 2H) (ArH), 8.41 (s, 1H, imidazo[4,5-b]pyridine 5-H);

Workup

temperatureto cool to room temperature
customthe solvents were removed in vacuo
customThe residue was absorbed on silica gel
washwas eluted with 2.5% methanol in ethyl acetate/dichloromethane (v/v; 1:1)
additiona solution of HCl in methanol (1.25 M; 0.8 ml) was added
additiondiethyl ether was added
filtrationThe yellow precipitate was collected by filtration
washwashed with ether

Sources & evidence

ORD record: ord-349182351d5549a1af79e8b522183e80
Source dataset: uspto-grants-2012_01
DOI: 10.6084/m9.figshare.5104873.v1
Patent number: US08088761B2

Reaction notes

Loading…