Indium → N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-amino-dibenzo[b,d]furan-1-carboxamide

HRID 1788087Notes

Reaction equation

HRID 1788087 reaction equation
[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:31])[C:7]=1[NH:8][C:9]([C:11]1[C:19]2[C:18]3[CH:20]=[C:21]([N+:24]([O-])=O)[CH:22]=[CH:23][C:17]=3[O:16][C:15]=2[C:14]([O:27][CH:28]([F:30])[F:29])=[CH:13][CH:12]=1)=[O:10].[In]>C(O)C.[Cl-].[NH4+]>[Cl:1][C:2]1[CH:3]=[N:4][CH:5]=[C:6]([Cl:31])[C:7]=1[NH:8][C:9]([C:11]1[C:19]2[C:18]3[CH:20]=[C:21]([NH2:24])[CH:22]=[CH:23][C:17]=3[O:16][C:15]=2[C:14]([O:27][CH:28]([F:29])[F:30])=[CH:13][CH:12]=1)=[O:10]

Participants

5

Reactant 2

HCID 5359967Indium3×HCID 10050271N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-nitro-dibenzo[b,d]furan-1-carboxamide2×

Product 1

HCID 10320896N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-amino-dibenzo[b,d]furan-1-carboxamide

Reagents, catalysts & solvents 2

HCID 702EthanolSolvent2×HCID 25517Ammonium ChlorideSolvent2×

Conditions

Temperature
80 °C

Procedure

First, N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-aminodibenzo[b,d]furan-1-carboxamide was prepared by reacting N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-nitro-dibenzo[b,d]furan-1-carboxamide (prepared using the procedure of Example 4) with indium in ethanol and saturated ammonium chloride. To a 1 L 3-neck round bottom flask, fitted with a mechanical stirrer and reflux condenser was added N-(3,5-dichloropyrid-4-yl)-4-difluoromethoxy-8-nitro-dibenzo[b,d]furan-1-carboxamide (22.00 g, 46.99 mmol), ethanol (308.0 mL), sat. aq. NH4Cl (132.0 mL) and indium (32.37 g, 281.93 mmol). The reaction mixture was heated to 80° C. for 4-5 h (reaction monitored by HPLC). Additional indium (5.40 g, 47.03 mmol) was added to the reaction and heated to 80° C. until HPLC indicated completion. After cooling to room temperature the reaction was evaporated to dryness. DMF (200 mL) was added to the solids and heated to 70-75° C. The solution was filtered, washed with DMF (100 mL) and concentrated to a volume of 50 mL in vacuo. Water (3 L) was added to the reaction mixture, the solid was filtered, washed with water (66 mL) and dried in a vacuum oven (65° C.) overnight. The dried product appeared as a yellow solid (17.77 g, 77.4%). Purity 87.84% by HPLC; 1H NMR (500 MHz, DMSO-d6): 5.11 (bs, 2H), 6.86 (dd, J=2.3, 8.8 Hz, 1H), 7.46-7.51 (m, 3H), 7.53 (t, J=73.0 Hz, 1H), 7.82 (d, J=8.0 Hz, 1H), 8.80 (s, 2H), 10.93 (bs, 1H) ppm. m/z 437.1 (M+).

Workup

  1. customprepared
  2. customTo a 1 L 3-neck round bottom flask, fitted with a mechanical stirrer
  3. temperaturereflux condenser
  4. custom(reaction monitored by HPLC)
  5. temperatureheated to 80° C. until HPLC
  6. temperatureAfter cooling to room temperature the reaction
  7. customwas evaporated to dryness
  8. additionDMF (200 mL) was added to the solids
  9. temperatureheated to 70-75° C
  10. filtrationThe solution was filtered
  11. washwashed with DMF (100 mL)
  12. concentrationconcentrated to a volume of 50 mL in vacuo
  13. additionWater (3 L) was added to the reaction mixture
  14. filtrationthe solid was filtered
  15. washwashed with water (66 mL)
  16. customdried in a vacuum oven (65° C.) overnight

Sources & evidence

ORD record
ord-0079d10c0e9d474da7f472c866bc5163
Source dataset
uspto-grants-2009_03
Patent number
US07511150B2

Reaction notes

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