Chloroacetone → HCID 86710165, compound

HRID 705389Notes

Reaction equation

HRID 705389 reaction equation
[CH:1]1([C:4]2[C:5]([N:23]([CH2:28][CH2:29][CH:30]([CH3:32])[CH3:31])[S:24]([CH3:27])(=[O:26])=[O:25])=[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:21])[NH2:20])[C:8]=3[CH:22]=2)[CH2:3][CH2:2]1.C(=O)([O-])O.[K+].Cl[CH2:39][C:40](=O)[CH3:41]>O1CCCC1.O.C(OCC)(=O)C>[CH:1]1([C:4]2[C:5]([N:23]([CH2:28][CH2:29][CH:30]([CH3:32])[CH3:31])[S:24]([CH3:27])(=[O:26])=[O:25])=[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]4[NH:20][C:40]([CH3:41])=[CH:39][N:21]=4)[C:8]=3[CH:22]=2)[CH2:2][CH2:3]1

Participants

7

Reactant 3

HCID 6571ChloroacetoneHCID 516893Potassium BicarbonateHCID 86710163HCID 86710163, compound

Product 1

HCID 86710165HCID 86710165, compoundYield 54.1%

Reagents, catalysts & solvents 3

HCID 962WaterSolventHCID 8028TetrahydrofuranSolvent2×HCID 8857Ethyl AcetateSolvent

Conditions

Temperature
75 °C

Procedure

In a 5-mL round bottom flask, a mixture of 5-cyclopropyl-2-(4-fluorophenyl)-6-(N-isopentylmethylsulfonamido)benzofuran-3-carboximidamide (34 mg, 0.061 mmol) and potassium hydrogencarbonate (18.30 mg, 0.183 mmol) in tetrahydrofuran (500 μL) and H2O (125 μL) was heated at reflux in an oil bath at 75° C. under a glass stoppered condenser with Teflon joint sleeve. A solution of chloroacetone (6.53 mg, 0.067 mmol) in tetrahydrofuran (125 μL) was added dropwise to the refluxing reaction mixture over 15 minutes. After 7 hours at reflux, the reaction was cooled to room temperature, diluted with ethyl acetate (25 mL), washed with H2O (2×10 mL) and brine (10 mL), dried over anhydrous Na2SO4, filtered, and concentrated by rotary evaporation. The residue was dissolved in 1 mL acetonitrile and 1 mL 0.1% trifluoroacetic acid in H2O, and purified by RP-C18 HPLC (Waters Prep LC, 40 mm Module with Nova-Pak HR C18 6 μm 40×100 mm Prep Pak cartridge) eluting with a 30 minute gradient of 95:5 0.1% trifluoroacetic acid in H2O/acetonitrile to 25:75 0.1% trifluoroacetic acid in H2O/acetonitrile, then 10 minutes to 100% CH3CN at 20 mL/minute. Pure fractions were concentrated by rotary evaporation and dried on a vacuum pump to afford the title compound as a white solid (20 mg, 0.033 mmol, 53%). 1H NMR (500 MHz, DMSO-d6) δ ppm 0.58-0.65 (m, 1H), 0.83 (t, J=6.56 Hz, 6H), 0.91-0.96 (m, 1H), 0.98-1.05 (m, 2H), 1.21-1.31 (m, 2H), 1.34-1.43 (m, 1H), 1.57-1.68 (m, 1H), 2.37 (d, J=0.92 Hz, 3H), 2.38-2.43 (m, 1H), 3.15 (s, 3H), 3.60-3.68 (m, 1H), 3.72-3.80 (m, 1H), 7.12 (s, 1H), 7.41 (t, J=8.85 Hz, 2H), 7.61 (s, 1H), 7.66 (dd, J=8.70, 5.34 Hz, 2H), 7.99 (s, 1H); MS (ESI+) m/z 496 (M+H)+, 991 (2M+H); MS (ESI−) m/z 494 (M−H)−, 530/532 (M+Cl)−, 608 (M+trifluoroacetic acid−H)−.

Workup

  1. temperaturewas heated
  2. temperatureAfter 7 hours at reflux
  3. temperaturethe reaction was cooled to room temperature
  4. washwashed with H2O (2×10 mL) and brine (10 mL)
  5. dry with materialdried over anhydrous Na2SO4
  6. filtrationfiltered
  7. concentrationconcentrated by rotary evaporation
  8. dissolutionThe residue was dissolved in 1 mL acetonitrile
  9. custom1 mL 0.1% trifluoroacetic acid in H2O, and purified by RP-C18 HPLC (Waters Prep LC, 40 mm Module with Nova-Pak HR C18 6 μm 40×100 mm Prep Pak cartridge)
  10. washeluting with a 30 minute gradient of 95:5 0.1% trifluoroacetic acid in H2O/acetonitrile to 25:75 0.1% trifluoroacetic acid in H2O/acetonitrile
  11. concentrationPure fractions were concentrated by rotary evaporation
  12. customdried on a vacuum pump

Sources & evidence

ORD record
ord-a2ad886301ce465eb3c6a7c0fdaf677d
Source dataset
uspto-grants-2015_11
Patent number
US09173887B2

Reaction notes

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