Methanol → 2-[2-Hydroxy-5-(6-methoxy-pyridin-2-yl)-phenyl]-1H-benzoimidazole-5-carboxylic acid {4-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenyl}-amide

HRID 470341Notes

Reaction equation

HRID 470341 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:39]=[CH:38][C:37]([C:40]2[CH:45]=[CH:44][CH:43]=[C:42]([O:46][CH3:47])[N:41]=2)=[CH:36][C:33]=1[CH:34]=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[NH:30][C:34]([C:33]5[CH:36]=[C:37]([C:40]6[CH:45]=[CH:44][CH:43]=[C:42]([O:46][CH3:47])[N:41]=6)[CH:38]=[CH:39][C:32]=5[OH:31])=[N: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 534857803,4-diamino-N-(4-(2-(4-methylpiperazin-1-yl)ethyl)phenyl)benzamideHCID 1361069522-Hydroxy-5-(6-methoxy-pyridin-2-yl)-benzaldehyde

Product 1

HCID 1784897082-[2-Hydroxy-5-(6-methoxy-pyridin-2-yl)-phenyl]-1H-benzoimidazole-5-carboxylic acid {4-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenyl}-amideYield 68%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent2×

Procedure

To a suspension of silica gel (0.8 g) in dichloromethane (5 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), 2-hydroxy-5-(6-methoxy-pyridin-2-yl)-benzaldehyde (114.6 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 (190 mg, 68%). 1H NMR (MeOH-d4) δ 2.26 (s, 3H), 2.37-2.72 (12H), 4.01 (s, 3H), 6.62 (d, J=9 Hz, 1H), 7.04 (d, J=9 Hz, 1H), 7.12 (d, J=9 Hz, 2H), 7.37 (d, J=6 Hz, 1H), 7.55 (d, J=9 Hz, 1H), 7.54-7.63 (2H), 7.76 (d, J=6 Hz, 1H), 8.04 (d, J=6 Hz, 1H), 8.13 (s, 1H), 8.53 (s, 1H). ESI-MS m/z 563 (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-f51dccc2052c4c589080fffb708f2f1d
Source dataset
uspto-grants-2014_01
Patent number
US08629147B2

Reaction notes

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