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

HRID 470339Notes

Reaction equation

HRID 470339 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[C:41]([O:46][CH3:47])=[N:42][CH:43]=[CH:44][CH:45]=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[N:30]=[C:34]([C:33]5[CH:36]=[C:37]([C:40]6[C:41]([O:46][CH3:47])=[N:42][CH:43]=[CH:44][CH:45]=6)[CH:38]=[CH:39][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 534857803,4-diamino-N-(4-(2-(4-methylpiperazin-1-yl)ethyl)phenyl)benzamideHCID 59784178HCID 59784178, compound

Product 1

HCID 1361068102-[2-Hydroxy-5-(2-methoxy-pyridin-3-yl)-phenyl]-3H-benzoimidazole-5-carboxylic acid {4-[2-(4-methyl-piperazin-1-yl)-ethyl]-phenyl}-amideYield 47%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of silica gel (6.0 g) in dichloromethane (20 mL) was added SOCl2 (1.5 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 (707.0 mg, 2.0 mmol) and 2-hydroxy-5-(2-methoxy-pyridin-3-yl)-benzaldehyde (458.5 mg, 2.0 mmol) were added, and the resulting mixture was stirred at the room temperature for 4 h. After methanol (10 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 (528 mg, 47%). 1H NMR (MeOH-d4) δ 2.25 (s, 3H), 2.35-2.71 (12H), 3.94 (s, 3H), 6.96 (m, 1H), 7.00 (d, J=9 Hz, 1H), 7.11 (d, J=9 Hz, 2H), 7.50-7.60 (4H), 7.66 (d, J=9 Hz, 1H), 7.79 (d, J=9 Hz, 1H), 8.06 (d, J=7 Hz, 1H), 8.10 (s, 1H), 8.14 (s, 1H). ESI-MS m/z 563 (MH+).

Workup

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

Sources & evidence

ORD record
ord-91d4e30f8cdc439cb2e6fc2f0737265f
Source dataset
uspto-grants-2014_01
Patent number
US08629147B2

Reaction notes

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