Ammonium formate → HCID 86710163, compound

HRID 705388Notes

Reaction equation

HRID 705388 reaction equation
[CH:1]1([C:4]2[C:5]([N:24]([CH2:29][CH2:30][CH:31]([CH3:33])[CH3:32])[S:25]([CH3:28])(=[O:27])=[O:26])=[CH:6][C:7]3[O:11][C:10]([C:12]4[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=4)=[C:9](/[C:19](=[N:21]/O)/[NH2:20])[C:8]=3[CH:23]=2)[CH2:3][CH2:2]1.C([O-])=O.[NH4+].CO.C(Cl)Cl>C(O)(=O)C.[Pd]>[CH:1]1([C:4]2[C:5]([N:24]([CH2:29][CH2:30][CH:31]([CH3:33])[CH3:32])[S:25]([CH3:28])(=[O:27])=[O:26])=[CH:6][C:7]3[O:11][C:10]([C:12]4[CH:17]=[CH:16][C:15]([F:18])=[CH:14][CH:13]=4)=[C:9]([C:19](=[NH:20])[NH2:21])[C:8]=3[CH:23]=2)[CH2:2][CH2:3]1

Participants

6

Reactant 3

HCID 2723923Ammonium formateHCID 21226129Dichloromethane methanolHCID 89955085HCID 89955085, compound

Product 1

HCID 86710163HCID 86710163, compoundYield 90.6%

Reagents, catalysts & solvents 2

HCID 23938PalladiumCatalystHCID 176Acetic AcidSolvent

Conditions

Temperature
120 °C

Procedure

In a 25-mL round bottom flask purged with nitrogen, (Z)-5-cyclopropyl-2-(4-fluorophenyl)-N′-hydroxy-6-(N-isopentylmethylsulfonamido)benzofuran-3-carboximidamide (200 mg, 0.422 mmol) was dissolved in glacial acetic acid (4 mL), and ammonium formate (133 mg, 2.112 mmol) and 10% Pd—C (100 mg, 0.094 mmol) were added. The mixture was heated in an oil bath at 120° C. for 2.5 hours. TLC (SiO2, 5% methanol/CH2Cl2) showed the reaction was complete. The reaction was cooled to room temperature, filtered through Celite® 545, washed with additional ethyl acetate, and concentrated the filtrate by rotary evaporation. The amidine acetic acid salt was dissolved in H2O (25 mL) and ethyl acetate (50 mL), the pH was adjusted with 1 N aqueous NaOH, and the mixture was stirred for 10 minutes, re-adjusting the aqueous pH˜12 as needed. The organic phase was washed with brine (25 mL), dried over anhydrous MgSO4, filtered, and concentrated by rotary evaporation co-evaporating with CH2Cl2/hexanes to afford the title compound as a yellow solid (175 mg). The material was 84% pure by analytical HPLC. MS (ESI+) m/z 458 (M+H)+, 915 (2M+H)+; MS (ESI−) m/z 456 (M−H)−.

Workup

  1. temperatureThe reaction was cooled to room temperature
  2. filtrationfiltered through Celite® 545
  3. washwashed with additional ethyl acetate
  4. concentrationconcentrated the filtrate
  5. customby rotary evaporation
  6. dissolutionThe amidine acetic acid salt was dissolved in H2O (25 mL)
  7. washThe organic phase was washed with brine (25 mL)
  8. dry with materialdried over anhydrous MgSO4
  9. filtrationfiltered
  10. concentrationconcentrated by rotary evaporation co-evaporating with CH2Cl2/hexanes

Sources & evidence

ORD record
ord-5e99792f31a84317bd99726e0ae2ae3e
Source dataset
uspto-grants-2015_11
Patent number
US09173887B2

Reaction notes

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