1-Hydroxybenzotriazole → HCID 178483020, compound

HRID 1428408Notes

Reaction equation

HRID 1428408 reaction equation
[Cl:1][C:2]1[CH:3]=[CH:4][C:5]2[S:9][C:8](=[O:10])[N:7]([CH2:11][C:12]([N:14]([CH3:19])[CH2:15][C:16](O)=O)=[O:13])[C:6]=2[CH:20]=1.[Cl:21][C:22]1[CH:23]=[C:24]([NH2:30])[C:25]([NH2:29])=[CH:26][C:27]=1[F:28].C1C=CC2N(O)N=NC=2C=1.CCN=C=NCCCN(C)C.Cl>CCOC(C)=O.CN(C=O)C>[ClH:1].[Cl:21][C:22]1[C:27]([F:28])=[CH:26][C:25]2[N:29]=[C:16]([CH2:15][N:14]([CH3:19])[C:12](=[O:13])[CH2:11][N:7]3[C:6]4[CH:20]=[C:2]([Cl:1])[CH:3]=[CH:4][C:5]=4[S:9][C:8]3=[O:10])[NH:30][C:24]=2[CH:23]=1

Participants

7

Reactant 4

HCID 757711-HydroxybenzotriazoleHCID 7357734-Chloro-5-fluoro-1,2-phenylenediamineHCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 117652690HCID 117652690, compound

Product 1

HCID 178483020HCID 178483020, compoundYield 128.8%

Reagents, catalysts & solvents 2

HCID 6228DimethylformamideSolventHCID 8857Ethyl AcetateSolvent

Procedure

To a mixture of N-[(5-chloro-2-oxo-1,3-benzothiazol-3(2H)-yl)acetyl]-N-methylglycine (150 mg), 4-chloro-5-fluorobenzene-1,2-diamine (81 mg), and DMF (5 mL) were added HOBt (77 mg) and WSC.HCl (107 mg), followed by stirring at room temperature overnight. The reaction mixture was diluted with EtOAc, and washed with water, a saturated aqueous NaHCO3 solution, and brine in this order, dried over Na2SO4, and then concentrated under reduced pressure. To the residue was added acetic acid (5 mL), followed by heating and stirring at 110° C. for 5 hours. The reaction mixture was cooled to room temperature and concentrated under reduced pressure. The residue was diluted with EtOAc. The organic layer was washed with a saturated aqueous NaHCO3 solution and brine in this order, dried over Na2SO4, and then concentrated under reduced pressure. The obtained solid was washed with EtOAc and then with MeOH, and suspended in MeOH (3 mL). 4 M hydrogen chloride/EtOAc (120 μL) was added thereto, followed by stirring at room temperature for 1 hour. The resulting solid was collected by filtration and then washed with MeOH to obtain N-[(6-chloro-5-fluoro-1H-benzimidazol-2-yl)methyl]-2-(5-chloro-2-oxo-1,3-benzothiazol-3(2H)-yl)-N-methylacetamide hydrochloride (146 mg).

Workup

  1. washwashed with water
  2. dry with materiala saturated aqueous NaHCO3 solution, and brine in this order, dried over Na2SO4
  3. concentrationconcentrated under reduced pressure
  4. additionTo the residue was added acetic acid (5 mL)
  5. temperatureby heating
  6. stirringstirring at 110° C. for 5 hours
  7. temperatureThe reaction mixture was cooled to room temperature
  8. concentrationconcentrated under reduced pressure
  9. additionThe residue was diluted with EtOAc
  10. washThe organic layer was washed with a saturated aqueous NaHCO3 solution and brine in this order
  11. dry with materialdried over Na2SO4
  12. concentrationconcentrated under reduced pressure
  13. washThe obtained solid was washed with EtOAc
  14. addition4 M hydrogen chloride/EtOAc (120 μL) was added
  15. stirringby stirring at room temperature for 1 hour
  16. filtrationThe resulting solid was collected by filtration
  17. washwashed with MeOH

Sources & evidence

ORD record
ord-6bfe46ad8fa5413eb0e41cc8a6960953
Source dataset
uspto-grants-2015_01
Patent number
US08937087B2

Reaction notes

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