1,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochloride → 4-Chloro-2-(difluoromethyl)-1-{[3-(2-pyridinyl)-1,2,4-oxadiazol-5-yl]methyl}-1H-indole-5-carbonitrile

HRID 1188342Notes

Reaction equation

HRID 1188342 reaction equation
[Cl:1][C:2]1[C:10]([C:11]#[N:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH:17]([F:19])[F:18])[N:6]2[CH2:13][C:14]([OH:16])=O.CCN=C=NCCCN(C)C.Cl.O[NH:33][C:34]([C:36]1[CH:41]=[CH:40][CH:39]=[CH:38][N:37]=1)=[NH:35]>ClCCCl>[Cl:1][C:2]1[C:10]([C:11]#[N:12])=[CH:9][CH:8]=[C:7]2[C:3]=1[CH:4]=[C:5]([CH:17]([F:19])[F:18])[N:6]2[CH2:13][C:14]1[O:16][N:35]=[C:34]([C:36]2[CH:41]=[CH:40][CH:39]=[CH:38][N:37]=2)[N:33]=1

Participants

5

Reactant 3

HCID 27239391,3-Propanediamine, N'-(ethylcarbonimidoyl)-N,N-dimethyl-, monohydrochlorideHCID 57800318[4-chloro-5-cyano-2-(difluoromethyl)-1H-indol-1-yl]acetic acidHCID 178513306HCID 178513306, compound

Product 1

HCID 249859654-Chloro-2-(difluoromethyl)-1-{[3-(2-pyridinyl)-1,2,4-oxadiazol-5-yl]methyl}-1H-indole-5-carbonitrileYield 59.3%

Reagents, catalysts & solvents 1

HCID 111,2-DichloroethaneSolvent

Procedure

To a suspension of [4-chloro-5-cyano-2-(difluoromethyl)-1H-indol-1-yl]acetic acid (0.020 g, 0.070 mmol) in DCE (2 mL), under N2 was added EDCl (0.015 g, 0.077 mmol) and the resulting mixture was stirred at rt. After 5 min, N-hydroxy-2-pyridinecarboximidamide (0.011 g, 0.077 mmol) was added. After stirring at rt for 30 min, the mixture was heated in a microwave at 150° C. for 20 min. Upon cooling, the mixture was partitioned between EtOAc and 0.1N HCl. The organic phase was washed with sat'd NaHCO3 solution and brine, dried (Na2SO4) and concentrated in vacuo. The residue was purified by flash chromatography (0-100% EtOAc-hexanes gradient) and the product was crystallized from CH2Cl2-MeOH-hexanes to give the title compound as a white solid (0.016 g, 59% yield): MS (ES) m/z 386 (M+1).

Workup

  1. stirringAfter stirring at rt for 30 min
  2. temperaturethe mixture was heated in a microwave at 150° C. for 20 min
  3. temperatureUpon cooling
  4. customthe mixture was partitioned between EtOAc and 0.1N HCl
  5. washThe organic phase was washed with sat'd NaHCO3 solution and brine
  6. dry with materialdried (Na2SO4)
  7. concentrationconcentrated in vacuo
  8. customThe residue was purified by flash chromatography (0-100% EtOAc-hexanes gradient)
  9. customthe product was crystallized from CH2Cl2-MeOH-hexanes

Sources & evidence

ORD record
ord-ffd8d39faa3945a8a12d60d54a296acc
Source dataset
uspto-grants-2014_03
Patent number
US08673948B2

Reaction notes

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