Piperazine → HCID 178513577, compound

HRID 2247160Notes

Reaction equation

HRID 2247160 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8](O)[C:9]2[CH:14]=[CH:13][C:12]([C:15]3[NH:19][C:18]4[CH:20]=[CH:21][C:22]([C:24]([NH2:26])=[O:25])=[CH:23][C:17]=4[N:16]=3)=[CH:11][CH:10]=2)=[CH:4][CH:3]=1.S(Cl)(Cl)=O.[NH:32]1[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]1>C(Cl)Cl>[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH:8]([N:32]2[CH2:37][CH2:36][NH:35][CH2:34][CH2:33]2)[C:9]2[CH:14]=[CH:13][C:12]([C:15]3[NH:19][C:18]4[CH:20]=[CH:21][C:22]([C:24]([NH2:26])=[O:25])=[CH:23][C:17]=4[N:16]=3)=[CH:11][CH:10]=2)=[CH:4][CH:3]=1

Participants

5

Reactant 3

HCID 4837PiperazineHCID 24386Thionyl ChlorideHCID 178513581HCID 178513581, compound

Product 1

HCID 178513577HCID 178513577, compoundYield 77%

Reagents, catalysts & solvents 1

HCID 6344DichloromethaneSolvent

Procedure

To a suspension of 2-{4-[(4-chloro-phenyl)-hydroxy-methyl]-phenyl}-1H-benzoimidazole-5-carboxylic acid amide (Example 20, 20.0 mg; 0.05 mmol) in CH2Cl2(10 mL) was added thionyl chloride (0.04 mL, 0.06 mmol), and the mixture was stirred at RT for 1 h. Solvent was removed under reduced pressure, and the residue was dried under high vacuum. The crude product was dissolved in acetonitrile (10 mL). Piperazine (21 mg, 0.24 mmol) was added, and the mixture was heated to reflux for 12 h. Solvent was removed under reduced pressure, and purification of the residue by chromatography (silica gel, 1% methanol saturated with ammonia/9% methanol/CH2Cl2) afforded 17 mg (77%) of the title compound. HPLC (Method A): Rt=6.44. MS (ESI−): mass calculated for C25H24ClN5, 445.2; m/z found, 444.6 [M−H]−. 1H NMR (500 MHz, CD3OD), δ 8.17 (br s, 1H), 8.09 (d, J=8.4 Hz, 2H), 7.82-7.80 (dd, J=8.5, 1.5 Hz, 1H), 7.66 (d J=8.4 Hz, 2H), 7.63 (br s, 1H), 7.50 (d, J=8.5 Hz, 2H), 7.35 (d, J=8.5 Hz, 2H), 4.56 (s, 1H), 3.31-3.27 (m, 8H).

Workup

  1. customSolvent was removed under reduced pressure
  2. customthe residue was dried under high vacuum
  3. dissolutionThe crude product was dissolved in acetonitrile (10 mL)
  4. temperaturethe mixture was heated
  5. temperatureto reflux for 12 h
  6. customSolvent was removed under reduced pressure, and purification of the residue by chromatography (silica gel, 1% methanol saturated with ammonia/9% methanol/CH2Cl2)

Sources & evidence

ORD record
ord-4117bff79b004b1f9672a1711873e895
Source dataset
uspto-grants-2010_03
Patent number
US07687639B2

Reaction notes

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