Benzaldehyde → HCID 178521201, compound

HRID 416702Notes

Reaction equation

HRID 416702 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]([Br:26])=[CH:4][N:3]=1.[CH:27](=O)[C:28]1[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=1.[O-]S(S([O-])=O)=O.[Na+].[Na+]>C(O)C>[Br: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:27]([C:28]3[CH:33]=[CH:32][CH:31]=[CH:30][CH:29]=3)[NH:1][C:2]2=[N:3][CH:4]=1

Participants

5

Reactant 3

HCID 240Benzaldehyde2×HCID 24489Sodium Dithionite2×HCID 468678032-(4-(2-amino-5-bromo-3-nitropyridin-4-yl)piperazin-1-yl)-N-(thiazol-2-yl)acetamide

Product 1

HCID 178521201HCID 178521201, compoundYield 60.2%

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

To a mixture 2-[4-(2-amino-5-bromo-3-nitro-pyridin-4-yl)-piperazin-1-yl]-N-thiazol-2-yl-acetamide (0.05 g, 0.11 mmol) and ethanol (3 ml) was added benzaldehyde (15 μL, 0.29 mmol) and a freshly prepared aqueous solution of Na2S2O4 (1M; 450 μL, 0.45 mmol). The reaction mixture was stirred at 80° C. for 16 h then more benzaldehyde (15 μL, 0.29 mmol) and 1M aq. Na2S2O4 (450 μL, 0.45 mmol) were added. The reaction mixture was stirred at 80° C. for another 16 h then concentrated in vacuo. The crude product was purified by chromatography on silica gel (100% dichloromethane to dichloromethane/ethyl acetate 6:4 to dichloromethane/ethyl acetate 1:1+0.5% methanol) to give the title compound as a pale yellow solid (0.033 g, 58%); 1H-NMR (500 MHz, DMSO-d6) 2.80 (broad s, 4H, piperazine N(CH2)2), 3.42 (s, 2H, CH2), 3.72 (broad s, 4H, piperazine N(CH2)2), 7.24 (d, 1H, J=3.4 Hz, thiazole 4-H or 5-H), 7.49 (d, 1H, J=3.4 Hz, Thiazole 4-H or 5-H), 7.54 (m, 3H, Ar—H), 8.20 (dd, 2H, J=1.5, 8.0 Hz, 2,6-Ar—H), 8.25 (s, 1H, imidazo[4,5-b]pyrazine 5-H), 11.92 (broad s, 1H, NHCO), 13.54 (broad s, 1H, imidazo[4,5-b]pyrazine NH); LC-MS (ESI, m/z) Rt=5.89 min—498/500 [(M+H+), Br isotopic pattern, 100%]; ESI-HRMS: Found: 498.0716, calculated for C21H21BrN7OS (M+H+): 498.0712.

Workup

  1. stirringThe reaction mixture was stirred at 80° C. for another 16 h
  2. concentrationthen concentrated in vacuo
  3. customThe crude product was purified by chromatography on silica gel (100% dichloromethane to dichloromethane/ethyl acetate 6:4 to dichloromethane/ethyl acetate 1:1+0.5% methanol)

Sources & evidence

ORD record
ord-1570483ebbd54caa8eb8f86720de12bf
Source dataset
uspto-grants-2012_01
Patent number
US08088761B2

Reaction notes

Loading…