Npc164516 → HCID 67544035, compound

HRID 2176109Notes

Reaction equation

HRID 2176109 reaction equation
Cl.[CH3:2][O:3][C:4]1[CH:9]=[CH:8][CH:7]=[CH:6][C:5]=1[NH:10]N.C[N:13]1[CH:17]2[CH2:18][C:19]([CH2:21][CH:14]1[CH2:15][CH2:16]2)=O.Cl.O1CCOC[CH2:24]1>C(O)C>[CH3:2][O:3][C:4]1[CH:9]=[CH:8][CH:7]=[C:6]2[C:5]=1[NH:10][C:15]1[CH2:24][CH:14]3[NH:13][CH:17]([C:16]2=1)[CH2:18][CH2:19][CH2:21]3

Participants

5

Reactant 3

HCID 79038Npc164516HCID 28494452-Methoxyphenylhydrazine HydrochlorideHCID 204431481,4-Dioxane hydrochloride

Product 1

HCID 67544035HCID 67544035, compound

Reagents, catalysts & solvents 1

HCID 702EthanolSolvent

Conditions

Temperature
80 °C

Procedure

A suspension of (2-methoxyphenyl)hydrazine hydrochloride (875 mg, 5.0 mmol; TCI-US), tropinone (696 mg, 5.0 mmol; Aldrich), and 4 M HCl-dioxane (2.5 mL, 10.0 mmol; Aldrich) in ethanol (10 mL) was heated to 80° C. for 16 hours. After cooling to room temperature, the reaction mixture was concentrated, basified with 5 N NaOH (aqueous), and then extracted with ethyl acetate (3×50 mL). The combined organic phase was concentrated and the residue was purified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 20-95% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)] to afford the title compound: 1H NMR (300 MHz, methanol-d4) δ ppm 1.62-1.80 (m, 1H), 1.97 (t, J=9 Hz, 1H), 2.24-2.38 (m, 2H), 2.47 (s, 3H), 2.57 (d, J=17 Hz, 1H), 3.25-3.36 (m, 1H), 3.65-3.73 (m, 1H), 3.92 (s, 3H), 4.34 (d, J=4Hz, 1H), 6.59 (d, J=8 Hz, 1H), 6.87-6.95 (m, 1H), 6.97-7.04 (m, 1H); MS (DCI/NH3) m/z 243 (M+H)+.

Workup

  1. temperatureAfter cooling to room temperature
  2. concentrationthe reaction mixture was concentrated
  3. extractionextracted with ethyl acetate (3×50 mL)
  4. concentrationThe combined organic phase was concentrated
  5. customthe residue was purified by reverse-phase HPLC [Waters XBridge™ RP18 column, 5 μm, 30×100 mm, flow rate 40 mL/minute, 20-95% gradient of methanol in buffer (0.1 M aqueous ammonium bicarbonate, adjusted to pH 10 with ammonium hydroxide)]

Sources & evidence

ORD record
ord-da186c9bc2b44d4b9955c1984c3f4cca
Source dataset
uspto-grants-2015_06
Patent number
US09063126B2

Reaction notes

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