Sulfuric Acid → HCID 45380758, compound

HRID 2176135Notes

Reaction equation

HRID 2176135 reaction equation
[Cl:1][C:2]1[CH:7]=[CH:6][C:5]([CH2:8][CH2:9][N:10]([C:12]2[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][CH:13]=2)N)=[CH:4][N:3]=1.[N:19]12[CH2:27][CH2:26][CH:23]([CH2:24][CH2:25]1)[C:22](=O)[CH2:21][CH2:20]2.S(=O)(=O)(O)O.[OH-].[Na+]>O1CCOCC1>[Cl:1][C:2]1[N:3]=[CH:4][C:5]([CH2:8][CH2:9][N:10]2[C:12]3[CH:17]=[CH:16][C:15]([CH3:18])=[CH:14][C:13]=3[C:21]3[CH2:20][N:19]4[CH2:27][CH2:26][CH:23]([C:22]2=3)[CH2:24][CH2:25]4)=[CH:6][CH:7]=1

Participants

6

Reactant 4

HCID 1118Sulfuric AcidHCID 14798Sodium HydroxideHCID 64203071-Azabicyclo[3.2.2]nonan-4-oneHCID 86640695HCID 86640695, compound

Product 1

HCID 45380758HCID 45380758, compound

Reagents, catalysts & solvents 1

HCID 312751,4-DioxaneSolvent

Conditions

Temperature
50 °C

Procedure

In a 50 mL round-bottom flask were combined 2-chloro-5-(2-(1-p-tolylhydrazinyl)-ethyl)pyridine (0.272 g, 1.039 mmol; Example 117D), and 1-azabicyclo[3.2.2]nonan-4-one (0.188 g, 1.351 mmol; Example 2A) in dioxane (5 mL). After 10 minutes of warming to 50° C., the suspension cleared. Concentrated sulfuric acid (0.277 mL, 5.20 mmol) was added and the mixture was heated at 80° C. After 1.5 hours, the mixture was cooled and concentrated to about 3 mL. The residue was dissolved in water (75 mL), basified with concentrated sodium hydroxide (30 mmol), extracted with chloroform (4×25 mL), dried over magnesium sulfate, and concentrated. The residue was purified by reverse-phase HPLC [Waters XBridge C18 5 μm OBD column, 30×100 mm, flow rate 40 mL/minute, 5-95% gradient of acetonitrile in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide) over 15 minutes] to give the title compound: 1H NMR (300 MHz, methanol-d4) δ ppm 1.63 (dddd, J=14.3, 9.3, 5.2, 2.4 Hz, 2H), 1.95 (ddt, J=13.6, 9.2, 5.2 Hz, 2H), 2.39 (s, 3H), 2.95 (m, 1H), 3.00 (m, 2H), 3.06 (t, J=6.4 Hz, 2H), 3.19 (ddd, J=14.1, 9.0, 5.2 Hz, 2H), 4.22 (s, 2H), 4.38 (t, J=6.4 Hz, 2H), 6.92 (dd, J=8.5, 1.4 Hz, 1H), 7.11 (br s, 1H), 7.12 (d, J=8.5 Hz, 1H), 7.25 (d, J=8.1 Hz, 1H), 7.36 (dd, J=8.3, 2.4 Hz, 1H), 7.79 (d, J=2.0 Hz, 1H); MS (DCI/NH3) m/z 366 (M+H)+.

Workup

  1. customIn a 50 mL round-bottom flask were combined
  2. temperaturethe mixture was heated at 80° C
  3. temperaturethe mixture was cooled
  4. concentrationconcentrated to about 3 mL
  5. dissolutionThe residue was dissolved in water (75 mL)
  6. extractionextracted with chloroform (4×25 mL)
  7. dry with materialdried over magnesium sulfate
  8. concentrationconcentrated
  9. customThe residue was purified by reverse-phase HPLC [Waters XBridge C18 5 μm OBD column, 30×100 mm, flow rate 40 mL/minute, 5-95% gradient of acetonitrile in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide) over 15 minutes]

Sources & evidence

ORD record
ord-1fe3e0371ee14eabb5876620e649d303
Source dataset
uspto-grants-2015_06
Patent number
US09063126B2

Reaction notes

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