Methanol → 2-(4-Hydroxy-2',5'-dimethoxy-biphenyl-3-yl)-3H-benzoimidazole-5-carboxylic acid {4-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenyl}-amide

HRID 470340Notes

Reaction equation

HRID 470340 reaction equation
O=S(Cl)Cl.[NH2:5][C:6]1[CH:7]=[C:8]([CH:27]=[CH:28][C:29]=1[NH2:30])[C:9]([NH:11][C:12]1[CH:17]=[CH:16][C:15]([CH2:18][CH2:19][N:20]2[CH2:25][CH2:24][N:23]([CH3:26])[CH2:22][CH2:21]2)=[CH:14][CH:13]=1)=[O:10].[OH:31][C:32]1[CH:37]=[CH:36][C:35]([C:38]2[CH:43]=[C:42]([O:44][CH3:45])[CH:41]=[CH:40][C:39]=2[O:46][CH3:47])=[CH:34][C:33]=1[CH:48]=O.CO>ClCCl>[CH3:26][N:23]1[CH2:24][CH2:25][N:20]([CH2:19][CH2:18][C:15]2[CH:14]=[CH:13][C:12]([NH:11][C:9]([C:8]3[CH:27]=[CH:28][C:29]4[N:30]=[C:48]([C:33]5[CH:34]=[C:35]([C:38]6[CH:43]=[C:42]([O:44][CH3:45])[CH:41]=[CH:40][C:39]=6[O:46][CH3:47])[CH:36]=[CH:37][C:32]=5[OH:31])[NH:5][C:6]=4[CH:7]=3)=[O:10])=[CH:17][CH:16]=2)[CH2:21][CH2:22]1

Participants

6

Reactant 4

HCID 887MethanolHCID 24386Thionyl ChlorideHCID 532205064-(2,5-Dimethoxyphenyl)-2-formylphenolHCID 534857803,4-diamino-N-(4-(2-(4-methylpiperazin-1-yl)ethyl)phenyl)benzamide

Product 1

HCID 1361067122-(4-Hydroxy-2',5'-dimethoxy-biphenyl-3-yl)-3H-benzoimidazole-5-carboxylic acid {4-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenyl}-amideYield 84%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of silica gel (0.8 g) in dichloromethane (3 mL) was added SOCl2 (0.6 mL) and the mixture was stirred at the room temperature for 1 h (gas was released from the reaction mixture). 3,4-Diamino-N-{4-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenyl}-benzamide (178.2 mg, 0.5 mmol), 4-hydroxy-2′,5′-dimethoxy-biphenyl-3-carbaldehyde (129.1 mg, 0.5 mmol) and 2 mL dichloromethane were added, and the resulting reaction mixture was stirred at the room temperature for 4 h. After methanol (5 mL) was added, the reaction mixture was stirred at room temperature for another 1 h and was evaporated under reduced pressure. The residue on silica gel was purified by chromatography (250:10:1 CH2Cl2/MeOH/28% aqueous NH4OH) to afford the title compound (217 mg, 84%). 1H NMR (MeOH-d4) δ 2.26 (s, 3H), 2.37-2.72 (12H), 3.73 (s, 3H), 3.77 (s, 3H), 6.80 (m, 1H), 6.94 (s, 1H), 6.95 (m, 1H), 7.03 (d, J=9 Hz, 1H), 7.13 (d, J=9 Hz, 2H), 7.49-7.64 (4H), 7.80 (d, J=9 Hz, 1H), 8.10 (s, 1H), 8.17 (s, 1H). ESI-MS m/z 592 (MH+).

Workup

  1. customthe resulting reaction mixture
  2. stirringwas stirred at the room temperature for 4 h
  3. stirringthe reaction mixture was stirred at room temperature for another 1 h
  4. customwas evaporated under reduced pressure
  5. customThe residue on silica gel was purified by chromatography (250:10:1 CH2Cl2/MeOH/28% aqueous NH4OH)

Sources & evidence

ORD record
ord-26017c801c4b4753a90a245555bfc97e
Source dataset
uspto-grants-2014_01
Patent number
US08629147B2

Reaction notes

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