Hydrochloric Acid → HCID 67545581, compound

HRID 2176166Notes

Reaction equation

HRID 2176166 reaction equation
Cl.[CH3:2][S:3]([C:6]1[CH:11]=[CH:10][C:9]([NH:12]N)=[CH:8][CH:7]=1)(=[O:5])=[O:4].[N:14]12[CH2:22][CH2:21][CH:18]([CH2:19][CH2:20]1)[C:17](=O)[CH2:16][CH2:15]2.Cl.O1CCOCC1>C(O)(=O)C>[CH3:2][S:3]([C:6]1[CH:11]=[CH:10][C:9]2[NH:12][C:17]3[CH:18]4[CH2:21][CH2:22][N:14]([CH2:15][C:16]=3[C:8]=2[CH:7]=1)[CH2:20][CH2:19]4)(=[O:5])=[O:4]

Participants

6

Reactant 4

HCID 313Hydrochloric AcidHCID 312751,4-DioxaneHCID 27351814-(Methylsulfonyl)phenylhydrazine hydrochlorideHCID 64203071-Azabicyclo[3.2.2]nonan-4-one

Product 1

HCID 67545581HCID 67545581, compound

Reagents, catalysts & solvents 1

HCID 176Acetic AcidSolvent

Conditions

Temperature
80 °C

Procedure

A mixture of (4-(methylsulfonyl)phenyl)hydrazine hydrochloride (1105 mg, 5.0 mmol; Acros), 1-azabicyclo[3.2.2]nonan-4-one (696 mg, 5.0 mmol; Example 2A), 4 N HCl in dioxane (2.5 mL, 10.0 mmol; Aldrich), and acetic acid (15 mL) was heated to 80° C. overnight (16 hours), then cooled to room temperature. The solvent was removed, and the residue was basified with 5 N sodium hydroxide and extracted with ethyl acetate (3×50 mL). The combined organic phases were concentrated in vacuo and purified by reverse-phase HPLC [Waters XBridge RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 20-99% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide) over 20 minutes] to afford the title compound: 1H NMR (300 MHz, methanol-d4) δ ppm 2.05-2.14 (m, 4H), 3.02-3.15 (m, 6H), 3.20-3.28 (m, 2H), 4.29 (s, 2H), 7.47 (d, J=8 Hz, 1H), 7.57-7.62 (m, 1H), 7.95 (d, J=1 Hz, 1H); MS (DCI/NH3) m/z 291 (M+H)+.

Workup

  1. temperaturecooled to room temperature
  2. customThe solvent was removed
  3. extractionextracted with ethyl acetate (3×50 mL)
  4. concentrationThe combined organic phases were concentrated in vacuo
  5. custompurified by reverse-phase HPLC [Waters XBridge RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 20-99% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide) over 20 minutes]

Sources & evidence

ORD record
ord-36b1be7271eb4b2d84de1d93b54cb7e9
Source dataset
uspto-grants-2015_06
Patent number
US09063126B2

Reaction notes

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