Acetic Acid → HCID 71114814, compound

HRID 1624046Notes

Reaction equation

HRID 1624046 reaction equation
[CH3:1][NH2:2].[CH3:3][C:4]1([CH3:19])[C:8](=O)[CH2:7][CH:6]([C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][C:11]=2[F:18])[CH2:5]1.O.[NH2:21]N.C(O)(=O)C>C(O)(C)C>[CH3:3][C:4]1([CH3:19])[C:8]2[NH:21][N:2]=[CH:1][C:7]=2[CH:6]([C:10]2[CH:17]=[CH:16][C:13]([C:14]#[N:15])=[CH:12][C:11]=2[F:18])[CH2:5]1

Participants

6

Reactant 4

HCID 176Acetic AcidHCID 6329MethylamineHCID 24654Hydrazine hydrate (1:1)HCID 71114786HCID 71114786, compound

Product 1

HCID 71114814HCID 71114814, compoundYield 99%

Reagents, catalysts & solvents 1

HCID 3776IsopropanolSolvent

Conditions

Temperature
90 °C

Procedure

Methanamine, 1,1-dimethoxy-N,N-dimethyl-(42.05 g, 352.84 mmol) is added to 4-(3,3-dimethyl-4-oxo-cyclopentyl)-3-fluoro-benzonitrile (34 g, 117.61 mmol) and the mixture is stirred at 90° C. for 16 hours. The mixture is cooled to ambient temperature and the excess DMF-DMA is evaporated to dryness. To the crude residue is added: isopropyl alcohol (163.20 mL), hydrazine monohydrate (11.78 g. 235.22 mmol), and acetic acid (20.22 mL, 352.84 mmol) and the mixture is stirred at 70° C. for 2 hours. The mixture is cooled to ambient temperature and the solvent evaporated to dryness. The mixture is poured into water (200 mL) and is extracted with MTBE (2×200 mL). The mixture is washed with brine, dried over MgSO4, filtered, and concentrated to dryness. The residue is purified by silica gel flash chromatography, eluting with hexane and 10% IPA to give the title compound (30 g, 99%). ES/MS (m/z) 256 (M+1), 1H NMR (300.16 MHz, DMSO) δ 12.62-12.60 (m, 1H), 7.82 (dd, J=1.5, 10.2 Hz, 1H), 7.62 (dd, J=1.5, 8.1 Hz, 1H), 7.42-7.34 (m, 1H), 4.52 (t, J=7.7 Hz, 1H), 2.73 (d, J=1.8 Hz, 1H), 2.07 (dd, J=8.1, 11.7 Hz, 1H), 1.25 (s, 6H).

Workup

  1. temperatureThe mixture is cooled to ambient temperature
  2. customthe excess DMF-DMA is evaporated to dryness
  3. additionTo the crude residue is added
  4. temperatureThe mixture is cooled to ambient temperature
  5. customthe solvent evaporated to dryness
  6. additionThe mixture is poured into water (200 mL)
  7. extractionis extracted with MTBE (2×200 mL)
  8. washThe mixture is washed with brine
  9. dry with materialdried over MgSO4
  10. filtrationfiltered
  11. concentrationconcentrated to dryness
  12. customThe residue is purified by silica gel flash chromatography
  13. washeluting with hexane and 10% IPA

Sources & evidence

ORD record
ord-1208737ec85642999501ea7a5efa7fe8
Source dataset
uspto-grants-2014_07
Patent number
US08778984B2

Reaction notes

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