1-Hydroxybenzotriazole → HCID 178483010, compound

HRID 1428405Notes

Reaction equation

HRID 1428405 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8](=[O:10])[N:7]([CH2:11][C:12]([OH:14])=O)[C:6]=2[CH:15]=1.Cl.Cl.[CH3:18][NH:19][CH2:20][C:21]1[NH:25][C:24]2[CH:26]=[CH:27][C:28]([C:30]([F:33])([F:32])[F:31])=[CH:29][C:23]=2[N:22]=1.C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>CCOC(C)=O.ClCCl>[ClH:1].[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[O:9][C:8](=[O:10])[N:7]([CH2:11][C:12]([N:19]([CH3:18])[CH2:20][C:21]3[NH:25][C:24]4[CH:26]=[CH:27][C:28]([C:30]([F:33])([F:32])[F:31])=[CH:29][C:23]=4[N:22]=3)=[O:14])[C:6]=2[CH:15]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 3921330(5-CHLORO-2-OXO-BENZOOXAZOL-3-YL)-ACETIC ACIDHCID 178483009HCID 178483009, compound

Product 1

HCID 178483010HCID 178483010, compoundYield 88.4%

Reagents, catalysts & solvents 2

HCID 6344DichloromethaneSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of (5-chloro-2-oxo-1,3-benzoxazol-3(2H)-yl)acetic acid (300 mg), N-methyl-1-[5-(trifluoromethyl)-1H-benzimidazol-2-yl]methanamine dihydrochloride (420 mg), and dichloromethane (10 mL) were added TEA (552 μL), HOBt (214 mg), and WSC.HCl (303 mg), followed by stirring at room temperature overnight. The reaction mixture was diluted with EtOAc. The organic layer was washed with water, a saturated aqueous NaHCO3 solution, and brine in this order, dried over Na2SO4, and then concentrated under reduced pressure. The resulting solid was collected by filtration and washed with EtOAc. To a mixture of the obtained solid (325 mg) and MeOH (5 mL) was added 4 M hydrogen chloride/EtOAc (330 μL), followed by stirring at room temperature for 1 hour. To the reaction mixture was added EtOAc. The resulting solid was collected by filtration and then washed with EtOAc to obtain 2-(5-chloro-2-oxo-1,3-benzoxazol-3 (2H)-yl)-N-methyl-N-{[5-(trifluoromethyl)-1H-benzimidazol-2-yl]methyl}acetamide hydrochloride (277 mg).

Workup

  1. washThe organic layer was washed with water
  2. dry with materiala saturated aqueous NaHCO3 solution, and brine in this order, dried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. filtrationThe resulting solid was collected by filtration
  5. washwashed with EtOAc
  6. additionTo a mixture of the obtained solid (325 mg) and MeOH (5 mL)
  7. additionwas added 4 M hydrogen chloride/EtOAc (330 μL)
  8. stirringby stirring at room temperature for 1 hour
  9. additionTo the reaction mixture was added EtOAc
  10. filtrationThe resulting solid was collected by filtration
  11. washwashed with EtOAc

Sources & evidence

ORD record
ord-16fe012b839a422d9fe97313f5e6555f
Source dataset
uspto-grants-2015_01
Patent number
US08937087B2

Reaction notes

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