1,2-Dichloroethane → HCID 178486895, compound

HRID 1012168Notes

Reaction equation

HRID 1012168 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:19][CH3:20])=[C:6]([CH:18]=1)[C:7]([NH:9][C:10]1[C:11]([C:15](O)=O)=[N:12][NH:13][CH:14]=1)=[O:8].[CH3:21][O:22][C:23]1[CH:24]=[C:25]([NH2:39])[C:26]([NH2:38])=[CH:27][C:28]=1[O:29][CH2:30]N1CCC(C)CC1.[CH2:40](Cl)CCl.[CH:44]1[CH:45]=[CH:46]C2N(O)N=[N:50][C:48]=2[CH:49]=1>CN(C=O)C>[Cl:1][C:2]1[CH:3]=[CH:4][C:5]([O:19][CH3:20])=[C:6]([CH:18]=1)[C:7]([NH:9][C:10]1[C:11]([C:15]2[NH:39][C:25]3[CH:24]=[C:23]([O:22][CH3:21])[C:28]([O:29][CH2:30][CH:44]4[CH2:49][CH2:48][N:50]([CH3:40])[CH2:46][CH2:45]4)=[CH:27][C:26]=3[N:38]=2)=[N:12][NH:13][CH:14]=1)=[O:8]

Participants

6

Reactant 4

HCID 111,2-DichloroethaneHCID 757711-HydroxybenzotriazoleHCID 671062864-Methoxy-5-(4-methyl-piperidin-1-ylmethoxy)-benzene-1,2-diamineHCID 178490649HCID 178490649, compound

Product 1

HCID 178486895HCID 178486895, compoundYield 0.5%

Reagents, catalysts & solvents 1

HCID 6228DimethylformamideSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of 4-(5-Chloro-2-methoxy-benzoylamino)-1H-pyrazole-3-carboxylic acid (0.22 g, 0.745 mmol), 4-Methoxy-5-(4-methyl-piperidin-1-ylmethoxy)-benzene-1,2-diamine (0.2 g, 0.745 mmol), EDC (0.173 g, 0.89 mmol) and HOBt (0.122 g, 0.89 mmol) in DMF (20 ml) was stirred at 80° C. for 1 hour then at ambient temperature for 16 hours and then reduced in vacuo. The residue was partitioned between EtOAc and saturated bicarbonate, the organic portion was washed with brine and dried (MgSO4), filtered and evaporated. The amide intermediate (150 mg), (LC/MS (acidic method): Rt 2.13, [M+H]+ 543) was dissolved in AcOH (5 ml) then heated at reflux for 4 hours. The reaction mixture was allowed to cool, reduced in vacuo, residue purified by preparative TLC to yield 5-Chloro-2-methoxy-N-{3-[6-methoxy-5-(1-methyl-piperidin-4-ylmethoxy)-1H-benzimidazol-2-yl-]1H-pyrazol-4-yl}-benzamide (2 mg). (LC/MS (acidic method): Rt 2.25, [M+H]+ 525)

Workup

  1. waitat ambient temperature for 16 hours
  2. customThe residue was partitioned between EtOAc and saturated bicarbonate
  3. washthe organic portion was washed with brine
  4. dry with materialdried (MgSO4)
  5. filtrationfiltered
  6. customevaporated
  7. dissolutionThe amide intermediate (150 mg), (LC/MS (acidic method): Rt 2.13, [M+H]+ 543) was dissolved in AcOH (5 ml)
  8. temperaturethen heated
  9. temperatureat reflux for 4 hours
  10. temperatureto cool
  11. custompurified by preparative TLC

Sources & evidence

ORD record
ord-9346cdf64545492589d5db45ab53d4f0
Source dataset
uspto-grants-2011_07
Patent number
US07977477B2

Reaction notes

Loading…